Objectives: The present study was performed to compare between two different fixation techniques and evaluate the histopathological changes which occur in temporomandibular joint (TMJ) of the dogs after surgically induced unilateral subcondylar fracture. Methods: Twenty- One healthy beagle male dogs with a mean age of 30 months were used in the present study. One of these animals was sacrificed to study the normal histology of the dog TMJ. The rest of the animals (20 animals) were operated on to induce a displaced unilateral subcondylar fracture then, the animals were randomly equally divided into 2 groups. After surgery, 5 dogs of each group were sacrificed at 2 months after surgery (Short-Term), while the remaining 5 were sacrificed at 4 months after surgery (Long-Term). The heads were separated and fixed, oscillating saw was used to articulate the entire TMJ. Specimens were decalcified, then the specimens were washed, grossed and sectioned in a sagittal plane. Tissue sections of 4 um thick were cut and stained with Hematoxylin and Eosin to be studied microscopically. Results: In group I animals, at 2 months after surgery, there was a marked hypertrophy of the articular fibrous covering of the condylar head, while at 4 months after surgery, the articular fibrous covering appeared thinner than normal, with marked decrease in thickness of the articular cartilage layer. In group II, at 2 months after plate insertion, the articular fibrous covering became hypertrophic, and the articular cartilage was markedly reduced but it was of a uniform thickness, while at 4 months after subcondylar fracture and plate fixation, no significant changes could be detected either in thickness or structure of the articular fibrous covering. Conclusion: Based on this study, it is obvious that the plate fixation group gave the most favorable results, when compared with maxillomandibular fixation (MMF) group.

The change in the value of the breaking energy is discussed here for selected steel grades used in building structures after subjecting the samples made of them to episodes of heating in the steady-state heating regime and then cooling in a simulated fire conditions. These changes were recorded based on the instrumented Charpy impact tests, in relation to the material initial state. The S355J2+N, 1H18N9T steels and also X2CrNiMoN22-5-3 duplex steel were selected for detailed analysis. The fire conditions were modelled experimentally by heating the samples and then keeping them for a specified time at a constant temperature of: 600°C (first series) and 800°C (second series), respectively. Two alternative cooling variants were investigated in the experiment: slow cooling of the samples in the furnace, simulating the natural fire progress, without any external extinguishing action, and cooling them in water mist simulating an extinguishing action by a fire brigade. The temperature of the tested samples was set at the level -20oC and alternatively at the level + 20oC. The conducted analysis is aimed at assessing the risk of sudden, catastrophic fracture of load-bearing structure made of steel degraded as a result of a fire previously occurred with different development scenarios.

The aim of the study was the comparison of conventional sintering versus additive manufacturing techniques for β-TCP bioceramics, focusing on mechanical properties and biocompatibility. A "critical" bone defect requires surgical intervention beyond simple stabilization. Autologous bone grafting is the gold standard treatment for such defects but it has its limitations. Alloplastic bone grafting using synthetic materials is becoming increasingly popular. The use of bone graft substitutes has increased significantly and current research was focused on optimizing these substitutes, whereas this study compares two existing manufacturing techniques and the thereby produced β-TCP implants. The 3D-printed β-TCP hybrid structure implant was fabricated using two components, a column structure and a freeze-foam, which were sintered together. The conventionally manufactured ceramics were made by pouring. Both scaffolds were characterized according to porosity, mechanical properties and biocompatibility. The hybrid structure had a total porosity of 74.4 ± 0.5%. Microporous β-TCP implants had a porosity of 43.5 ± 2.4%, while macroporous β-TCP implants had a porosity of 61.81%. Mechanical testing revealed that the hybrid structure had a compressive strength of 10.4 ± 6 MPa, significantly lower than the microporous β-TCP implant’s with 32.9 ± 8.7 MPa. Biocompatibility evaluations showed a steady increase in cell proliferation over time for all β-TCP implants, with minimal cytotoxicity. This study provides valuable insight into the potential of additive manufacturing for β-TCP bioceramics in the treatment of bone defects.

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.

Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents. In this review, we summarize the latest advancements in ABCs. More importantly, we provide an overview and outlook on novel antibacterial agent-loaded bone cements, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides, etc. Offering novel perspectives for designing ABCs and treating bone infections.

Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disease (LSD) caused by deficiency of a hydrolase enzyme, N-acetylgalactosamine-6-sulfate sulfatase, and characterized clinically by mainly musculoskeletal manifestations. The mechanisms underlying bone involvement in humans are typically explored using invasive techniques such as bone biopsy, which complicates analysis in humans. We compared bone proteomes using DDA and SWATH-MS in wild-type and MPS IVA knockout mice to obtain mechanistic information about the disease. Our findings reveal over 1000 dysregulated proteins in knockout mice, including those implicated in oxidative phosphorylation, oxidative stress (reactive oxygen species), DNA damage, and iron transport, and suggest that lactate dehydrogenase may constitute a useful prognostic and follow-up biomarker. Identifying biomarkers that reflect MPS IVA clinical course, severity, and progression have important implications for disease management.

Mandibular third molar is the most frequently impacted tooth. Mandibular third molar impaction bears consequences on the adjacent mandibular second molar (MSM) like bone loss. It can be identified initially using orthopantomography (OPG). The objective is to compare the changes in the bone level distal to MSM between patients with extracted and non-extracted impacted man-dibular third molars (IMTM) using OPG. In this retrospective case-control study, 160 archived (OPGs) of 80 patients visiting the Dental Hospital of the University of Barcelona (HOUB) were randomly selected. The participants were stratified into two groups. The study group involved measuring the bone level distal to the mandibular second molar before and after the extraction of the IMTM. The control group, on the other hand, had bone levels measured twice within 3–6-month period without the extraction of the IMTM. The mean ages of patients in study and control groups were 35.5 ± 15.45 and 33 ± 16.49, respectively. Study group demonstrated signifi-cant (p < 0.05) bone gain after extraction, whereas control group demonstrated significant bone loss (p < 0.0001) after follow-up. Bone improvements were observed distal to the mandibular second molar after the extraction of the IMTM compared to those in control group.

Salmon aquaculture generates a substantial volume of waste material, offering potential for biomaterial production. This industry produces significant waste, which can be repurposed for various biological applications, particularly in biomaterial production for tissue engineering with pertinent applications in osteo-conduction, osteo-induction, and clinical/surgical bone regeneration and repair. The process involves a standardized pre-treatment stage aimed at minimizing biological waste content. Subsequently, the treatment stage, contingent on the chosen methodology, facilitates the removal of proteins, lipids, and other compounds, leaving the mineral phase as a valuable substrate. The selection of the optimal method, whether alkaline hydrolysis, calcination, or NaOH hydrolysis, for obtaining this substrate necessitates thorough examination through chemical, physical, and biological assessments, including Raman Spectroscopy and X-Ray Diffraction. This study aims to identify the most efficient approach for hydroxyapatite production derived from salmon waste.

Mesenchymal stromal cells (MSCs) are a subset of heterogeneous non-hematopoietic fibro-blast-like cells which play important roles in tissue repair, inflammation, and immune modula-tion. MSCs residing in the bone marrow microenvironment (BMME) functionally interact with hematopoietic stem progenitor cells regulating hematopoiesis. However, MSCs have also emerged in the last years as key regulator of tumor microenvironment. Indeed, they are now con-sidered as active players in the pathophysiology of hematologic malignancies rather than passive by-standers in hematopoietic microenvironment. Once the malignant event occurs, the BMME acquires cellular, molecular, and epigenetic abnormalities affecting tumor growth and progres-sion. In this context, MSC behavior is affected by signals coming from cancer cells. Furthermore, it has been showed that stromal cells themselves play a major role in several hematological malig-nancies’ pathogenesis. This bidirectional crosstalk creates a functional tumor niche unit wherein tumor cells acquire a selective advantage over their normal counterpart and are protected from drug treatment. It is therefore of critical importance to unveil the underlying mechanisms which activate a protumor phenotype of MSCs for defining unmasked vulnerabilities of hematological cancer cells which could be pharmacologically exploited to disrupt the tumor/MSCs coupling. The present review will focus on the current knowledge about MSC dysfunction mechanisms in the BMME of hematological cancers, sustaining tumor growth, immune escape, and cancer pro-gression.

This review will deal with the most relevant unmet needs and clinical questions concerning scintigraphy with bone tracers in ATTR-CA, providing expert opinions on possible future developments in the clinical application of these radiotracers, in order to offer practical information for interpretation of nuclear images to physicians involved in the care of patients with this ATTR-CA.

The importance of various markers such as sclerostin, Dickkopf-1 (DKK-1), Irisin, receptor activator of NF-kB ligand (RANKL), and Vitamin D have been well studied in bone metabolism. Additionally, inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and Interleukine-6 (IL-6) have been identified to hinder muscle protein synthesis, leading to the loss of muscle and strength. However, a research gap exists in the understanding their role in muscle function and physical activity. Therefore, this study aims to explore the serum levels of sclerostin, DKK-1, irisin, IL-6, RANKL, Vitamin D, and TNF-α and assess their relationships with upper and lower body strength in young adults. In this study, 38 college-aged students 18-23 years participated and completed the protocols. The participants’ lower and upper body strength were assessed by the vertical jump test (Just Jump, Probotic, AL) with a Tendo FitroDyne (Tendo Sports Machines, Trencin, Slovak Republic) and handgrip (HG) dynamometry (Takei Scientific Instruments, Yashiroda, Japan), respectively. Fasting morning blood samples were analyzed for serum levels of the biomarkers by ELISA. The results indicate significant sex differences in sclerostin, DKK-1, irisin, and vitamin D levels (p<0.05). Furthermore, a positive association was observed between sclerostin, DKK-1, and vitamin D, with lower body muscle performance variables (p<0.05). Conversely, a significant negative correlation was observed between TNF-α and upper-body muscle performance variables (p<0.05). The results suggest that these markers may have a distinct effect on muscle performance, underscoring the need for further investigation to elucidate the concept of muscle-bone crosstalk.

CETP activity reduces plasma HDL-cholesterol concentrations, a correlate of increased risk of atherosclerotic events. However, our recent findings suggest that CETP expression in macrophages promotes an intracellular antioxidant state, reduces free cholesterol accumulation and phagocytosis, and attenuates pro-inflammatory gene expression. To determine whether CETP expression in macrophages affects atherosclerosis development, we transplanted bone marrow from transgenic mice expressing simian CETP or non-expressing littermates into hypercholesterolemic LDL receptor deficient mice. CETP expression did not change lipid-stained lesion areas but decreased macrophage content (CD68), neutrophil accumulation (LY6G) and aorta content of young male transplanted mice and decreased LY6G, TNF-α, iNOS and nitrotyrosine (3-NT) in aged female transplanted mice. These findings suggest that CETP expression in bone marrow-derived cells reduces inflammatory features of atherosclerosis. These novel mechanistic observations may help explain the failure of CETP inhibitors to reduce atherosclerotic events in humans.

The injectable hydrated calcium phosphate bone-like paste (hCPP) have been developed with suitable nanoscale characteristics and unindered injection through 23G standard needles. In vitro assays showed the cytocompatibility of hCPP with mesenchymal embryonic C3H10T1/2 cell cultures. The hCPPs were identified to be composed of aggregated nano-sized particles with sphere-like shapes with low crystallinity. The ability of serum proteins (FBS) to adsorb on hCPP particles was also studied. The hCPP demonstrated high protein adsorption capacity, thereby indicating its potential in various biomedical applications. The results of the in vivo assay upon subcutaneous injection in Wistar rats indicated the nontoxicity and biocompatibility of experimental hCPP, as well as the gradual resorption of hCPP, comparable to the period of bone regeneration. The data obtained are of great interest for the development of commercial highly effective osteoplastic materials for bone tissue regeneration and augmentation.

Bone metabolism is a complex process which is influenced by the activity of bone cells (e.g., osteocytes, osteoblasts, osteoclasts), the effect of some specific biomarkers (e.g., parathyroid hormone, vitamin D, alkaline phosphatase, osteocalcin, osteopontin, osteoportegerin, osterix, RANKL, Runx2) and the characteristic signaling pathways (e.g., RANKL/RANK, Wnt/β, Notch, BMP, SMAD). Some phytochemical compounds such as flavonoids, tannins, polyphenols, anthocyanins, terpenoids, polysaccharides, alkaloids and others presented a beneficial and stimulating effect in the bone regeneration process due to pro-estrogenic activity, antioxidant and anti-inflammatory effects and modulation of bone signaling pathways. Lately, nanomedicine has emerged as an innovative concept for new treatments in bone related pathologies envisaged by incorporation of medicinal substances in nanometric systems for oral or local administration, as well as in nanostructured scaffolds with huge potential in bone tissue engineering.

Methacrylated silk (Sil-MA) is a chemically modified silk fibroin specifically designed to be crosslinkable under UV light. This allows the structuring of this material throught additive manufacturing techniques and then to easily prototype patient specific construct. In this study we used Sil-MA to produce single layer crosslinked structures that can be withdrawal and ejected recovering their shape after rehydration. A complete chemical and physical characterization of the material has been conducted. Additionally, we tested the material biocompatibility according to the International Standard Organization protocols (ISO 10993) ensuring the possibility to use it in future trials. The material was also tested to verify its ability to support the osteogenesis. Two different additive manufacturing techniques have been tested (a Digital Light Processing (DLP) UV projector and a pneumatic extrusion technique) to develop Sil-MA grid. Finally, we provide a proof-of-concept that the printed Sil-MA structures are injectable.

Notwithstanding the advances achieved in the last decades in the field of synthetic bone substitutes, the development of biodegradable 3D scaffolds with ideal mechanical and biological properties remains an unattained challenge. In this work, a novel approach is explored to produce synthetic bone grafts mimicking the complex bone structure using additive manufacturing. For the first time, scaffolds were produced, using an extrusion technique, composed of a thermoplastic polymer, polycaprolactone (PCL), hydroxyapatite nanoparticles (HANp), and polyethylene glycol diacrylate (PEGDA). These scaffolds were further compared with two groups of scaffolds: one composed of PCL and another of PCL and HANp. After production, optimisation and characterisation of these scaffolds, an in vitro evaluation was performed using human dental pulp stem/stromal cells (hDPSCs). Through the findings it was possible to conclude that PEGDA scaffolds were successfully produced presenting networks of interconnected channels, presenting hydrophilic properties (15.15 4.06°), adequate mechanical performance (10.41MPa 0.934), and allowing a cell viability significantly superior to the other groups analysed. To conclude, findings in this study demonstrated that PCL, HANp and PEGDA scaffolds may have promising effects on bone regeneration and might open new insights for 3D tissue substitutes.

Tadalafil is a selective phosphodiesterase type-5 (PDE5) inhibitor that is approved for the treatment of men with erectile dysfunction (ED) and/or benign prostate hyperplasia (BPH) associated symptoms. Besides its classical actions on PDE5 within the genitourinary tract, where the specific enzyme expression is maximal, it may exert different systemic effects. This is mainly due to the pleiotropic distribution of PDE5 enzyme throughout human (and animal) body, where it can exert protective effects in different clinical conditions. Recently, it has been demonstrated that tadalafil may display novel actions on androgen receptor (AR) expression and activity, cytochrome P19a1 (Cyp19a1) and estrogen receptor β (ERβ) expression in different in vitro systems, such as adipose, bone and prostate cancer cells where it can act as a selective modulator of steroid hormone production. This may determine novel potential mechanism(s) of control in pathophysiologic pathways. In this review we summarize basic research and translational results applicable to the use of tadalafil in the treatment of different clinical conditions.

Neutrophils as innate immune cells primarily act as first responders in acute infection and directly maintain inflammatory responses. However, a growing body of evidence suggests that neutrophils also bear the potential to mediate chronic inflammation by exhibiting memory-like features. We recently showed that priming by serial doses of lipopolysaccharide (LPS) from gram-negative bacteria can trigger opposing memory-like responses (exaggerated inflammation, i.e. trained sensitivity or suppression of inflammation, i.e. tolerance) depending on the LPS-dose. We now asked whether this observation could also hold true for lipoteichoic acid (LTA) from gram-positive S. aureus. We found comparable effects of LTA on neutrophil priming as seen for LPS. Low-dose (1 ng/mL) LTA-priming promoted increased production of pro-inflammatory mediators (i.e., TNF-α, IL-6, ROS), whereas high-dose (10 µg/mL) results in contrary reactions supporting anti-inflammatory responses by increased IL-10 and declined pro-inflammatory capacity. In vitro neutrophil recruitment was similarly regulated by LTA -priming. Investigation of signalling patterns revealed TLR2/MyD88-mediated regulation of NFκB-p65 through intermediate PI3Ks/MAPK. Collectively, our data suggest a previously unknown capacity of neutrophils to be differentially primed by varying doses of LTA, endorsing memory-like features in neutrophils.

In bone tissue engineering, ceramics have been the choice due to their excellent biological properties. But the paradigm changed with the discovery of bioactive glasses (BGs) in 1969 by Larry Hench and co-workers, due to their ability to bond to living tissues through the formation of an interfacial bone-like hydroxyapatite layer when the bioglass was put in contact with biological fluids in vivo. Among a number of tested compositions, the one exhibiting the highest bioactivity index is the well-known trademarked 45S5 Bioglass®. The topic received increasing attention particularly after 1985 when this material entered in the market of biomedical devices, inspiring many other investigations aiming at further exploring the in vitro and in vivo performances of this BG, or developing other related BG compositions. The research efforts gradually revealed a number of shortcomings of 45S5 Bioglass®, mostly derived from its high sodium content, initially intended to decrease the melting temperature and accelerating the degradation of the silicate network over time. But the extensive release of sodium from 45S5 Bioglass® in the biological fluids creates a high pH cytotoxic environment. Other serious drawbacks include a fast degradation rate, and a poor sintering ability, which hinders the reliable fabrication of porous scaffolds. Therefore, sol-gel was regarded as an attractive alternative to prepare alkali-free BG compositions. The process uses inorganic and/or organic precursors, which undergo hydrolysis and condensation at room-temperature, being less costly. When properly conducted, the sol-gel process might result in amorphous structures with all the components intimately mixed at the atomic scale. Moreover, developing new better performing materials for bone tissue engineering is a growing concern, as the ageing of the world’s population leads to lower bone density and osteoporosis. This work describes the sol-gel synthesis of a novel quaternary silicate-based BG with the composition 60 SiO2 – 34 CaO – 4 MgO – 2 P2O5 (mol%) was prepared using acidified distilled water as single solvent. By controlling the kinetics of the hydrolysis and condensation steps, an amorphous glass structure could be obtained. The results of XRD of samples calcined within the temperature range from 600-900 ºC demonstrated that amorphous nature was maintained until 800 ºC, followed by partial crystallization at 900 ºC. The specific surface area, an important factor in osteoconduction, was also evaluated over different temperatures, ranging from 160.6 ± 0.8 m2/g at 600 ºC down to 2.2 ± 0.1 m2/g at 900 ºC, being accompanied consistent changes in average pore size and agreeing pore size distribution. The immersion of the BG particles in simulated body fluid (SBF) led to the formation of an extensive apatite layer on its surface. These overall results indicate the proposed material is very promising for biomedical applications in bone regeneration and tissue engineering.

SAA is an acute phase protein that elevates under inflammatory circumstance. The serum level of SAA was associated with the progression of inflammation in numerous diseases. However, little attention was paid to the correlation between SAA and ONFH. In this study, SAA was found risen in the femoral head of osteonecrosis patients through proteomics analysis and further confirmed by ELISA. Furthermore, SAA was proven affecting bone metabolism in rBMSCs. It facilitated the proliferation of rBMSCs whereas it suppressed the osteogenic differentiation of rBMSCs and accelerated the adipogenic differentiation of rBMSCs. Thus, we deem that serum amyloid A, which is a vital acute phase protein in inflammation, affected bone metabolis and plays an imperative role in the pathophysiological process of ONFH.

We present an investigation on the fracture of a mold, comparing it with a normal part using specific techniques, such as EDX, SEM, and AES. The EDX analysis revealed that the composition of the normal part was consistent with that of low carbon steel, mainly comprising Fe and C. In contrast, the fractured part exhibited cracks due to nonconforming nonmetallic inclusions and reticular carbides, with fractures resulting from microporosity agglomeration and cleavage fracture. The SEM and AES analyses further presented the causes of mold fracture, highlighting the mechanism by which dimples on the specimen edge contributed to the fracture. The EDX analysis confirmed that the mold experienced thermal brittleness during use. To enhance mold durability and extend its lifespan, a double-pulse electrodeposition method was employed to create a NiCo alloy coating as a replacement for the Cr layer on the metal surface. The coating exhibited a smooth and scratch-free surface. The prepared NiCo special coating significantly increased the mold yield strength by approximately 313.8%, facilitated a 13% increase in plastic deformation, and reduced fracture strain by 25%, effectively preventing mold fracture and 3improving its service life.

Fibre reinforced cementitious materials (FRC) have become an attractive alternative for structural applications. Among such FRC, steel and polyolefin fibre reinforced concrete and glass fibre reinforced concrete are the most used ones. However, in order to exploit the properties of such materials structural designers need constitutive relations that reproduce FRC fracture behaviour accurately. This contribution analyses the suitability of multilinear softening functions combined with a cohesive crack approach for reproducing the fracture behaviour of the FRC previously mentioned. The implementation performed accurately simulates the fracture behaviour while being versatile, robust and efficient from a numerical point of view.

In Zambia wild edible terrestrial orchids are used to produce a local delicacy called chikanda, which has become increasingly popular throughout the country. Commercialization puts orchid populations in Zambia and neighbouring countries at risk of overharvesting. Hitherto, no study has documented which orchid species are traded on local markets, as orchid tubers are difficult to identify morphologically. In this study, the core land-plant DNA barcoding markers rbcL and matK were used in combination with nrITS to determine which species were sold on Zambian markets. Eighty-two interviews were conducted to determine harvesting areas, as well as possible sustainability concerns. By using nrITS DNA barcoding, a total of 16 orchid species in six different genera could be identified. Both rbcL and matK proved suitable to identify the tubers up to genus- or family level. Disa robusta, Platycoryne crocea and Satyrium buchananii were identified most frequently and three previously undocumented species were encountered on the market. Few orchid species are currently listed on the global IUCN Red List. Local orchid populations and endemic species could be at risk of overharvesting due to the intensive and indiscriminate harvesting of chikanda orchids and we therefore encourage increased conservation assessment of terrestrial African orchids.

Maxillary sinus augmentation with a lateral approach (MSA) is a well-established treatment. In this prospective study, we evaluated risk factors for postoperative bone-graft displacement and report the clinical application of long-term resorbable GMEM-B-2 (L-lactic acid/-caprolactone [P(LA/CL)]) as a barrier membrane to cover the open window in the lateral wall in MSA. Twenty-four patients underwent MSA according to the relevant criteria; CT data obtained before and 1 week (1W) and 5–6 months (5M) post-MSA, bone height changes, bone height reduction rates at 1W and 5M post-MSA, bone-graft displacement measurements, and risk factors were examined. All patients showed bone height increments (p &lt; 0.005). However, no difference was observed between 1W and 5M post-MSA. Bone-graft displacement was observed in eight patients; the reduction rate from 1W to 5M post-MSA was 8.38% ± 4.88%. Sex, septa, maxillary sinus floor–palatal bone distance, and maxillary sinus floor–natural mouth distance were associated with bone-graft displacement (p &lt; 0.05). Height from the maxillary sinus floor to the palatal bone and the sinus angle influenced the augmentation amount (p &lt; 0.05). The L-lactic acid/ε-caprolactone [P(LA/CL)] membrane compared favourably with other membranes and may be useful as a barrier membrane for the MSA open window.

Infrastructure development is rapidly increasing, driving up demand for concrete, a key construction material. Cement and aggregate are essential constituents, with global cement production reaching 4.1 billion metric tons in 2011 and CO2 emissions hitting 1.7 billion metric tons by 2024, a significant contributor to carbon emissions. To address this, alternative constituents like Rice Husk Ash (RHA) and Animal Bone Powder (ABP) are proposed. With rice husk comprising 20% of rice weight and a substantial cattle population in Bangladesh, RHA and ABP offer promising alternatives. This study examines the benefits and limitations of incorporating RHA and ABP into cement, focusing on concrete strength and permeability. By replacing varying percentages of cement with RHA and ABP simultaneously, experiments evaluate their impact on concrete properties after 28 days of curing. The research aims to identify the optimal combination for sustainable concrete production, reducing environmental impact by curbing waste generation and pollution. Results show that compressive strength increases and permeability decreases with up to 5% replacement of RHA and ABP, highlighting their potential for enhancing concrete performance while mitigating environmental concerns.

Limb-salvage surgery is the first choice for treatment of primary or metastatic bone tumors when possible to perform. Rehabilitation plays a major role after surgery, with the aim of improving function and maintaining the highest possible quality of life. Megaprostheses are currently the most frequent type of limb reconstruction used to treat the bone defect after tumor resection and The Modular Universal Tumor And Revision System (MUTARS®)is currently among the most used tumor and revision systems. Several studies have evaluated the causes and rate of failure of this system, but only few studies investigated the rehabilitative outcomes in terms of function and quality of daily life. The aim of this narrative review is to explore the correlations between functional outcomes and quality of life after implant of MUTARS® prostheses surgery in patients with bone tumor of the lower extremities. A comprehensive search was conducted on PubMed and Scopus using the following MESH terms: “MUTARS”, “Megaprosthesis”, “bone”, “tumors”, “metastasis”, “lower limb”, “rehabilitation”, “outcome”, “quality of life”, and 12 studies were included. The most frequent oncological pathology was found to be primitive bone tumors treated with modular prosthesis. Outcome measures used were Henderson et al classification, HHS, MSTS, VAS, ROM,LSR, KPS and quality of life questionnaire. Reconstruction of the lower limbs with the MUTARS® system seemed to be a valid treatment option after bone tumor resection. Rehabilitation after MUTARS® surgery is very relevant, but currently, functional and rehabilitative outcomes are inadequately represented in the literature. Therefore, further studies are needed to define best rehabilitation protocols in clinical practice after oncological orthopedic surgery.

Study of alterations in Osteoarthritis (OA) of Glypicans 1 to 6 (GPCs) and Notum in plasma, bone marrow mesenchymal stromal cells (BM-MSCs) and osteoblasts. Plasma levels of GPCs and Notum were measured of 25 patients and 24 healthy subjects. In addition, BM-MSCs from eight OA patients and eight healthy donors were cultured during 21 days with culture me-dium and osteogenic medium. Protein and gene expression levels of GPCs and Notum were de-termined by ELISA and qPCR at 0, 7 ,14 and 21 days. GPC5 and Notum have been found de-creased in OA patients’ plasma. OA BM-MSCs showed downexpression of GPC6 and upregula-tion of Notum. A decrease in GPC5 and Notum proteins and an increase in GPC3 were found. During osteogenic differentiation, elevated GPC2, 4, 5, 6 and Notum mRNA levels and decreased GPC3 were observed in OA. Furthermore, the protein levels of GPC2, GPC5 and Notum de-creased and GPC3 increased. Glypicans and Notum are altered in BM-MSCs and during osteo-genic differentiation from patients with OA. Furthermore, GPC5 and Notum can be proposed as new biomarkers of the pathology. The alterations found indicate that Notum could be a prom-ising therapeutic strategy for Osteoarthritis.

This study investigates the effect of scaffold architecture on bone regeneration, focusing on 3D-printed polylactic acid-bioceramic calcium phosphate (PLA-bioCaP) composite scaffolds in rabbit femoral condyle critical defects. To assess their influence on bone healing and scaffold performance, we explored two distinct scaffold designs, alternate and helical laydown patterns. The scaffolds were meticulously characterized for pore size, strut thickness, porosity, pore accessibility, and mechanical properties. The in vivo efficacy of these scaffolds was evaluated using a rabbit femoral condyle critical defect model. Our findings indicate that both scaffold architectures are biocompatible and support bone formation. The helical scaffolds, characterized by larger pore sizes and higher porosity, demonstrated significantly greater bone regeneration than the alternate structures. However, their lower mechanical strength presented limitations for use in load-bearing sites. This study highlights the importance of scaffold architecture in bone tissue engineering and underscores the need to balance porosity and mechanical strength for optimal bone regeneration. The findings provide crucial insights for the design of 3D- printed scaffolds in clinical applications, particularly in the context of critical-sized bone defects. The study also outlines potential areas for future research, including exploring hybrid scaffold designs to achieve optimal porosity without compromising mechanical integrity.

The human mandible's cancellous bone, which is characterized by its unique porosity and directional sensitivity to external forces, is crucial for sustaining biting stress. Traditional CAD models fail to fully represent bone's anisotropic structure and thus depend on simple isotropic assumptions. For our research, we use the latest versions of nTopology and Creo Parametric software to make biomimetic Voronoi lattice models that accurately reflect the complex geometry and mechanical properties of trabecular bone. The porosity of human cancellous bone is accurately modeled in this work using biomimetic Voronoi lattice models. The porosities range from 70% to 95%, which can be achieved by changing the pore sizes to 1.0 mm, 1.5 mm, 2.0 mm, and 2.5 mm. Finite element analysis (FEA) was used to examine the displacements, stresses, and strains acting on dental implants with a buttress thread, abutment, retaining screw, and biting load surface. The results show that the Voronoi model accurately depicts the complex anatomy of the trabecular bone in the human jaw, compared to standard solid block models. The ideal pore size for biomimetic Voronoi lattice trabecular bone models is 2 mm, taking into account both the von Mises stress distribution over the dental implant, screw retention, cortical bone, cancellous bone, and micromotions. This pore size displayed balanced performance by successfully matching natural bone's mechanical characteristics. Advanced finite element analysis (FEA) improves biomechanical understanding of how bones and implants interact by creating more accurate models of biological problems and dynamic loading situations. This makes biomechanical engineering better.

Background: biophysical stimulation therapy, and in particular Pulsed Electromagnetic Fields (PEMFs) and capacitively coupled electric fields (CCEFs) has significantly increased in the last twenty years. For this, it is necessary to have clear information regarding the efficacy, the therapeutic indication and the expected objectives. Methods: we conducted a narrative review taking into consideration different types of studies with different areas of application. The objective was to take into consideration and analyze the different fields of use and the relevant information present in the literature. Results: There is unanimous opinion regarding the usefulness of applying biophysical therapy on the bone compartment both in terms of the tissue healing process and the symptoms associated with this situation. Differently, but no less importantly, in the joint compartment positive opinions were observed mainly on the inflammatory and catabolic process, however, at present,we did not report evidence regarding cartilaginous tissue regeneration. Conclusion: the effectiveness of PEMFs and CCEFs on the bone healing process in the Orthopedic and Traumatology fields is consolidated evidence in the literature. We have also found positive results on symptoms and patient compliance with rehabilitation therapies. Therefore, notable application can be envisaged in the fields of Prosthetic Surgery and Sports Medicine.

Background: Brain-derived neurotrophic factor (BDNF) has attracted increasing attention as a therapeutic agent because of its potentially biological activities, including osteogenesis. However, the molecular mechanisms involved in the osteogenic activity of BDNF have not been fully investigated. This study aimed to investigate the action of BDNF on the osteoblast differentiation in bone marrow stromal cells, and its influence on signaling pathways. Methods: Preosteoblast cells (MC3T3-E1), bone marrow-derived stromal cells (ST2), and a direct 2D co-culture system were treated with BDNF. The effect of BDNF on cell proliferation was determined using the CCK-8 assay. Osteoblast differentiation was assessed based on alkaline phosphatase (ALP) activity and staining and the protein expression of multiple osteoblast markers. Calcium accumulation was examined by Alizarin red S staining. Results: BDNF significantly increased ALP activity, calcium deposition, and the expression of osteoblast differentiation-related proteins, such as ALP, osteopontin, etc. in both ST-2 and the MC3T3-E1 and ST-2 co-culture system. Moreover, the effect of BDNF on osteogenic differentiation was diminished by blocking tropomyosin receptor kinase B as well as inhibiting c-Jun N-terminal kinase and p38 MAPK signals. Conclusion: Our study results showed positive effect of BDNF on osteogenesis. It provides essential evidence for clinical applications of BDNF in treating osteoporosis.

Adipose stem cells (ASCs) have multilineage differentiation capacity and hold great potential for regenerative medicine. Compared to bone-marrow-derived mesenchymal stem cells (bmMSCs), ASCs are easier to isolate from abundant sources with significantly higher yields. It is generally accepted that bmMSCs show age-related changes in their proliferation and differentiation potentials, whereas this aspect is still controversial in the case of ASCs. In this review, we evaluated the existing data on the effect of donor age on the osteogenic potential of human ASCs. Overall, a poor agreement has been achieved because of inconsistent findings in the previous studies. Finally, we attempted to delineate the possible reasons behind the lack of agreements reported in the literature. ASCs represent a heterogeneous cell population and the osteogenic potential of ASCs can be influenced by donor-related factors such as age, but also gender, lifestyle, and the underlying health and metabolic state of donors. Furthermore, future studies should consider experimental factors in in-vitro conditions, including passaging, cryopreservation, culture conditions, variations in differentiation protocols, and readout methods.

Antibiotic-loaded bone cements are widely used in orthopedic surgery. However, they present issues such as a short antibiotic release time and the antibiotic resistance. These challenges necessitate the development of novel antibacterial bone cements. Non-leaching bone cement containing antibacterial motifs represents a promising advancement in this direction. Antibacterial motifs are incorporated into the cement either covalently or non-covalently, and while they will not be released, they will still exhibit surface antibacterial activity. This review comprehensively examines the structure and antimicrobial activity of prevalent non-leaching antimicrobial bone cements. Additionally, it delves into the characteristics of current methods employed for detecting surface antimicrobial activity. Finally, the future research direction of non-leaching antibacterial bone cement is discussed, with a specific focus on innovative antibacterial motifs, the mechanisms underlying non-leaching antibacterial properties, and the potential synergies achievable by combining non-leaching antibacterial bone cement with traditional antibiotics.

Bone fractures are very common in the geriatric population and poses a great economic burden worldwide. While traditional methods for repairing bone defects have primarily been autografts, there are several drawbacks limiting its use. Bone graft substitutes have been used as alternative strategies to improve bone healing. However, there remains several impediments to achieving the desired healing outcomes. Injectable hydrogels have become attractive scaffold materials for bone regeneration given their high performance in filling irregularly sized bone defects, ability to encapsulate cells and bioactive molecules, and mimic the native ECM of bone. We investigated the use of an injectable chitosan-based hydrogel scaffold to promote differentiation of preosteoblasts in vitro. The hydrogels were characterized by evaluating cell homogeneity, cell viability, rheological and mechanical properties, and differentiation ability of preosteoblasts in hydrogel scaffolds. Cell-laden hydrogel scaffolds exhibited shear thinning behavior and the ability to maintain shape fidelity after injection. The CNC-CS hydrogels exhibited higher mechanical strength and significantly upregulated the osteogenic activity and differentiation of preosteoblasts as shown by ALP activity assays and histological analysis of hydrogel scaffolds. These results suggest that this injectable hydrogel is suitable for cell survival, can promote osteogenic differentiation of preosteoblasts, and structurally support new bone growth.

Based on previous studies of our group in which we demonstrated that dalbavancin loaded in bone cement had good elution capacity for the treatment of biofilm-related periprosthetic infections, we now assess the anti-biofilm activity of dalbavancin and compare it with that of vancomycin up to a 3-month period. We performed an in vitro model based on calculation of percentage reduction of log cfu/ml counts of sonicated steel discs contaminated with Staphylococci and further exposed to bone cement discs loaded with 2.5% or 5% vancomycin and dalbavancin at each study period (24 hours, 48 hours, 1 week, 2 weeks, 6 weeks, 3 months). In addition, we tested the anti-biofilm activity of eluted vancomycin and dalbavancin at each study period based on a 96-well plate model assessing percentage reduction of metabolic activity. Overall, dalbavancin showed a significant concentration decrease from 2 weeks of incubation and maintain its anti-biofilm activity up to 3 months, whereas, despite vancomycin showed a significant decrease at 1w and then it gradually increased, its anti-biofilm activity was significantly lower. Dalbavancin percentage reduction cfu/ml counts were higher than those of vancomycin, both at 2.5% and 5% concentrations. Reduction of log cfu/ml counts were higher for S. epidermidis than for S. aureus, being more notable for 5% dalbavancin at month 3. In addition, percentage reduction of metabolic activity also decreased at 3 months in 5% dalbavancin and 5% vancomycin, being more notable in the last.

The aim of this study was to evaluate the effects of autologous microfragmented adipose tissue (MFAT), obtained by mechanical fragmentation, on radiographic bone healing in dogs subjected to tibial plateau levelling osteotomy (TPLO). Twenty dogs with unilateral cranial cruciate disease were enrolled and randomly assigned to the treatment group (MFAT) or the control group (NT). The MFAT group underwent TPLO and autologous MFAT intra-articular administration while the NT group underwent TPLO alone. The adipose tissue was collected from the thigh region and MFAT was obtained by mechanical fragmentation at the end of the surgery. The patients were subjected to X-ray exam preoperatively, immediately postoperatively (T0) and at 4 (T1) and 8 (T2) weeks postoperatively. Two radiographic scores that had previously been described for the evaluation of bone healing after TPLO were used. A 12-point scoring system (from 0 = no healing to 12= complete remodelling) was used at T0, T1 and T2, while a 5-point scoring system (from 0 = no healing to 4 = 76%–100% of healing) was used at T1 and T2. The median healing scores were significantly higher at T1 and T2 for the MFAT group compared with the NT group for the 12-point (p < 0.05) and 5-point (p < 0.05) scoring systems. The intra-articular injection of autologous microfragmented adipose tissue can accelerate bone healing after TPLO without complications.

The osseointegration process in and around additively manufactured (AM) lattice structures of a new titanium alloy, Ti–19Nb–14Zr, was evaluated. Three different implants, including lattices with increasing high sidewalls gradually closing them, were designed, manufactured and implanted in the tibia and metatarsal bone of two sheep for twelve weeks. After removal, they were characterized with X-ray computed tomography (XCT). The 3D XCT images were segmented using machine learning. The bone-interface implant (BII) and bone-implant contact (BIC) were studied. The results show that, since AM naturally leads to high roughness surface finish, the wettability of the implant is increased. The new alloy possesses an increased affinity to the bone enhancing the quality of osseointegration. The lattice provides crevices, in which the biological tissue can jump in and cling. The combination of these factors is pushing ossification beyond its natural limits. Therefore, the quality and speed of the ossification and osseointegration in and around these Ti–19Nb–14Zr AM laterally closed lattice implants open the possibility of bone spline key of prostheses. This enables the stabilization of the implant into the bone while keeping the possibility of punctual hooks allowing the implant to be removed more easily if required.

Calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) regulates bone remodeling through its effects on osteoblasts and osteoclasts. However, its role in osteocytes, the most abundant bone cell type, and the master regulator of bone remodeling, remains unknown. Here we report that the conditional deletion of CaMKK2 from osteocytes using Dentine matrix protein 1 (Dmp1)-8kb-Cre mice led to enhanced bone mass only in female mice owing to a suppression of osteoclasts. Conditioned media isolated from female CaMKK2-deficient osteocytes inhibited osteoclast formation and function in in vitro assays, indicating a role for osteocyte-secreted factors. Proteomics analysis revealed significantly higher levels of extracellular calpastatin, a specific inhibitor of calcium-dependent cysteine proteases calpains, in female CaMKK2 null osteocyte conditioned media, compared to media from female control osteocytes. Further, exogenously added non-cell permeable recombinant calpastatin domain I elicited a marked, dose-dependent inhibition of female wild-type osteoclasts and depletion of calpastatin from female CaMKK2-deficient osteocyte conditioned media reversed the inhibition of matrix resorption by osteoclasts. Our findings reveal a novel role for extracellular calpastatin in regulating female osteoclast function and unravel a novel CaMKK2-mediated paracrine mechanism of osteoclast regulation by female osteocytes.

Age estimation in dental radiographs Orthopantomography (OPG) is a medical imaging technique that physicians and pathologists utilise for disease identification and legal matters. For example, for estimating post-mortem interval, detecting child abuse, drug trafficking, and identifying an unknown body. Recent development in automated image processing models improved the age estimation's limited precision to an approximate range of +/- one year. While this estimation is often accepted as accurate measurement, age estimation should be as precise as possible in most serious matters, such as homicide. Current age estimation techniques are highly dependent on manual and time-consuming image processing. Age estimation is often a time-sensitive matter in which the image processing time is vital. Recent development in Machine learning-based data processing methods has decreased the imaging time processing; however, the accuracy of these techniques remains to be further improved. We proposed an ensemble method of image classifiers and transfer learning techniques to enhance the accuracy of age estimation using OPGs from one year to a couple of months (1-3-6). This hybrid model is based on convolutional neural networks (CNN) and K nearest neighbours (KNN). The hybrid (HCNN-KNN) model was used to investigate 1,922 panoramic dental radiographs of patients aged 15 to 23. These OPGs were obtained from the various teaching institutes and private dental clinics in Malaysia. To minimise the chance of overfitting in our model, we used the principal component analysis (PCA) algorithm and eliminated the features with high correlation. To further enhance the performance of our hybrid model, we performed systematic image pre-processing. We applied a series of classifications to train our model. We have successfully demonstrated that combining these innovative approaches has improved the classification and segmentation and thus the age-estimation outcome of the model. Our findings suggest that our innovative model, for the first time, to the best of our knowledge, successfully estimated the age in classified studies of one year old, six months, three months and one-month-old cases with accuracies of 99.98, 99.96, 99.87, and 98.78 respectively.

Hybrid scaffolds based on bioactive glass (BAG) particles (<38µm), covalently linked to the gelatin (G*), using 3-glycidoxypropyltrimethoxysilane (GPTMS), have been studied for bone bioengineering. In this study, two glass compositions (13-93 and 13-93B20 [where 20% of the SiO2 was replaced with B2O3]) were introduced in the gelatin matrix. The Cfactor (Gelatin/GPTMS molar ratio) was kept constant at 500. The hybrids obtained were found to be stable at 37°C, in solution; condition at which pure gelatin is liquid. All hybrids were characterized by in vitro dissolution in TRIS solution (for up to 4 weeks) and Simulated Body Fluid (SBF) (for up to 2 weeks). Samples processed with 13-93B20 exhibit a faster initial dissolution and significantly faster precipitation of a hydroxyapatite (HA) layer. The faster ion release and HA precipitation recorded from the G*/13-93B20 samples, is attributable to the higher reactivity of borosilicate compared to the silicate glass. MC3T3-E1 cells behavior, in direct contact with the hybrids, was investigated, showing that the cells were able to proliferate and spread on the developed biomaterials. Tailoring the glass composition allows to better control the material’s dissolution, biodegradability, and bioactivity. Bioactive (especially with 13-93B20 BAG), and biocompatible, the hybrids are promising for bone application.

Translational medicine requires facile experimental systems to replicate the dynamic biological systems of diseases. Drug approval continues to lag, partly due to incongruencies in the research pipeline that traditionally involve 2D models, which could be improved with 3D models. The bone marrow (BM) poses challenges to harvest as an intact organ making it difficult to study disease processes such as breast cancer (BC) survival in BM, and to effective evaluation of drug response in BM. Furthermore, it is a challenge to develop 3D BM structures due to its weak physical properties, and complex hierarchical structure and cellular landscape. To address this, we leveraged 3D bioprinting to create a BM structure with varied methylcellulose (M):alginate (A) ratios. We selected hydrogels containing 4% (w/v) M and 2% (w/v) A, which recapitulates rheological and ultrastructural features of the BM while maintaining stability in culture. This hydrogel sustained the culture of two key primary BM microenvironmental cells found at the perivascular region, mesenchymal stem cells and endothelial cells. More importantly, the scaffold showed evidence of cell autonomous dedifferentiation of BC cells to cancer stem cell properties. This scaffold could be the platform to create BM models for various disease and also for drug screening.

The link between scoliotic deformity and bone metabolism in adolescent idiopathic scoliosis (AIS) has not been well researched. Moreover, the data concerning the cross-talk between fat tissue content/hormonal activity and bone markers in this group of patients are lacking. The objective of this study was to correlate the extent of scoliotic-curve severity with the bone turnover vs. leptin level and nutritional status in girls with AIS. The study encompassed 77 AIS girls, aged 14.7 ± 2.17 years. Scoliotic curve severity assessed by Cobb’s angle was categorized as mild (10-19o) moderate (20-39º) or severe (≥40º). Corrected height, weight, waist and hip circumferences were measured and body mass index (BMI), corrected height Z-score, BMI Z-score and waist/height ratio (WHtR) were calculated for the entire group. Body composition parameters: fat mass (FAT), fat-free mass (FFM) and predicted muscle mass (PMM) were determined using a bioelectrical impedance analyzer. Bone turnover markers (osteocalcin (OC) and amino terminal of collagen cross-links NTx) and leptin levels were assessed in serum. Multiple regression analysis showed that, OC, NTx (negatively with p<0.05) and leptin (positively with p<0.01) were significantly associated with curve severity in AIS girls. Moreover, Cobb’s angle was positively correlated with W/HtR (p<0.01)and FAT (p<0.05). One-way analysis of variance (ANOVA) revealed significant differences in leptin (p<0.05 vs. mild only), OC (p<0.05 vs. mild and moderate)) and W/HtR (p<0.01 and p<0.05 vs. mild and moderate respectively) between the three AIS severity subgroups. OC was significantly lower in the severe AIS subgroup, while leptin and W/HtR were significantly higher. Significant correlations between leptin and anthropometrical parameters as BMI z-score and W/HtR were shown. Leptin level correlated also significantly with BMI z score (p<0.001), W/HtR (p<0.0001) and body composition parameters (p<0.000001). Moreover, there was a significant negative correlation between NTx and leptin level (p<0.05). Bone metabolism in AIS girls seems to be altered and significantly related to the scoliotic curve severity. Leptin may be a crucial link in the cross-talk between bone turnover and body composition in this group of patients. Further studies concerning this topic are needed.

The standard care for metastatic breast cancer (MBC) is systemic therapies with imbrication of focal treatment for symptoms. Recently, thanks to implementation of radiological and metabolic exams and development of new target therapies, oligometastatic and oligoprogressive settings are even more common, paving the way to a paradigm change of focal treatments role. In fact, according to immunophenotype, radiotherapy can be considered with radical intent in these settings of patients. The aim of this literature review is to analyse available clinical data on prognosis of bone metastases from breast cancer and benefits of available treatments for developing a practical guide for clinicians.

Liver cirrhosis leads to hepatic dysfunction and life-threatening conditions. Though clinical efficacy of autologous bone marrow-drived mesenchymal stem cells (BM-MSC) transplantation in alcoholic cirrhosis (AC) was demonstrated, the relevant mechanism has not been elucidated. We aimed to identify predictive factors and gene/pathways for responders after autologous BM-MSC transplantation. Fifty-five patients with biopsy-proven AC underwent autologous BM-MSC transplantation. The characteristics of responders who showed improvement in fibrosis score (≥ 1) after transplantation were compared with those of non-responders. BM-MSCs were analyzed with cDNA microarrays to identify genes and pathways that were differentially expressed in responder after transplantation. Thirty-three patients (66%) were responders. In the multivariate analysis, initial high Laennec score (p=0.007, odds ratio 3.73) and performance of BM-MSC transplantation (p=0.033, odds ratio 5.75) were predictive factors for responder. Three genes (olfactory receptor 2L8, microRNA4520-2, and chloride intracellular channel protein 3) were upregulated in responders and 11 metabolic pathways (inositol phosphate, ATP-binding cassette transporters, protein kinase signaling, extracellular matrix-receptor interaction, endocytosis, phagosome, hematopoietic cell lineage, adipocytokine, peroxisome proliferator-activated receptor, fat digestion/absorption, and insulin resistance) were upregulated in non-responders (p<0.05). BM-MSC transplantation is warranted treatment for AC patients with high Laennec score. Cell-based therapy utilizing response-relating genes or pathway can be treatment candidate.

Malignant cells cultured in three-dimensional (3D) models have been found to be phenotypically and biochemically different from their counterparts cultured conventionally. Since most of these studies employed solid tumor types, how 3D culture affects multiple myeloma (MM) cells is not well understood. Here, we compared MM cells (U266 and RPMI8226) in a 3D culture model with those in conventional culture. While the conventionally cultured cells were present in single cells or small clusters, MM-3D cells grew in large spheroids. We discovered that STAT3 was the pathway that was more activated in 3D in both cell lines. The active form of STAT3 (phospho-STAT3 or pSTAT3), which was absent in MM cells cultured conventionally, became detectable after 1-2 days in 3D culture. This elevated pSTAT3 level was dependent on the 3D environment, since it disappeared after transferring to conventional culture. STAT3 inhibition using a pharmacological agent, Stattic, significantly decreased the cell viability of MM cells and sensitized them to bortezomib in 3D culture. Using an oligonucleotide array, we found that 3D culture significantly increased the expression of several known STAT3 downstream genes implicated in oncogenesis. Since most primary MM tumors are naturally STAT3-active, studies of MM in 3D culture can generate results that are more representative of the disease.

Aluminium alloys are used for fabrication of fuel clad of research grade nuclear reactors as well as of several types of core components of high flux research reactors. In order to carry out design and safety analysis of these components, their mechanical and fracture properties are required by the designer. In this work, experiments have been conducted on tensile specimens machined from an aluminium alloy block to evaluate the material stress-strain curve. For evaluation of fracture properties, experiments have been conducted on disc shaped compact tension specimens in order to determine the fracture toughness of aluminium alloy. From crystal plasticity based finite element analysis and experimental data, a material damage parameter for prediction of crack initiation has been evaluated. The variation of the parameter for various values of initial a/W ratios of the disc-shaped CT specimens have been studied. It was observed that the damage parameter is independent of crack geometry and hence, it qualifies as transferable material property which can be used to predict crack initiation in a component of this material subjected to different kinds of loading conditions. In addition, the JR curves of the disc-shaped CT specimens have also been evaluated from experiments. The material damage parameter has also been used to study the crack initiation in single crystal fracture specimens with two different orientations. It was observed that the [111] orientation is more susceptible to crack initiation and propagation compared to the [100] orientation as the damage parameter is high in the ligament of the specimen ahead of the crack-tip for the same level of load. The results of the experiments and the material damage parameter shall be helpful for integrity analysis of fuel clad of research reactors as well as components of high flux research reactors.

Background: In physiotherapy, a classic muscle-bone concept is used to translate basic and clinical anatomy. By defining the anatomical structures from superficial to deeper layers which frame the ArthroMyoFascial complex, our aim is to offer clinicians a comprehensive concept of fasciae within the muscle-bone concept. Method: Narrative review and ultrasound observation. Results: Based on literature and ultrasound skeletonization, the ArthroMyoFascial complex has been defined. This model clarifies fascial continuity at the joint level, describing anatomical structures from skin to deeper layers, including superficial fascia, deep fascia, myofascia including skeletal muscle fibers, and arthrofascia all connected via connective tissue linkages. This model enhances understanding of the muscle-bone concept within the larger ArthroMyoFascial complex. Conclusion: The ArthroMyofascial complex consists of multiple layers from superficial to deeper anatomical structures, namely the skin, superficial fascia, deep fascia, myofascia including muscle fibers, and arthrofascia, all linked within a connective tissue matrix. This model indicates that it is a force-transmitting system from the skin to the bone. This information is crucial for manual thera-pists, including physiotherapists, osteopaths, chiropractors, and massage therapists, as they all work with fasciae within the musculoskeletal domain. Understanding fascia within the mus-cle-bone concept enhances clinical practice, aiding in therapeutic testing, treatment, reporting, and multidisciplinary communication, which is vital for musculoskeletal and orthopedic rehabilitation.

The aim of this study was to evaluate the use of a flexible synthetic polymer bone graft to provide implant stability in the absence of implant stability during implant placement in a dense cortical bone model. Sockets were prepared on polyurethane blocks according to the standard implant socket drilling protocol in the control group, both oversizing and deepening in group 2, and oversizing only in group 3. In groups 2 and 3, flexible synthetic polymer bone grafts were placed in the sockets prior to implant placement. The implants were placed at bone level in all groups. The highest torque value obtained was recorded as the insertion torque. 75 implant sites in 3 groups were included in the study. The torque values of the implants in the control group were significantly higher than those of the implants with the oversized and deepened sockets and the oversized-only sockets (p&lt;0.05; p&lt;0.01).The torque values of the implants with the oversized and deepened sockets were significantly higher than those of the implants with the oversized-only sockets (p&lt;0.01). In this study, flexible synthetic polymer bone graft was shown to be effective in achieving implant stability in the management of implants with loss of primary stability.

Oncostatin M (OSM), an inflammatory cytokine belonging to interleukin-6 superfamily, is recognized as an essential factor secreted by osteal macrophages to orchestrate bone remodelling. Osteoprotegerin (OPG) produced by osteoblasts regulates osteoclastogenesis. We previously demonstrated that bone morphogenetic protein-4 (BMP-4) stimulates OPG synthesis in osteoblast-like MC3T3-E1 cells, and that SMAD1/5/8(9), p38 mitogen-activated protein kinase (MAPK), and p70 S6 kinase positively regulates the OPG synthesis. The present study is aimed to investigate the effect of OSM on BMP-4-stimulated OPG synthesis in osteoblasts. OSM suppressed the release and the mRNA expression of OPG upregulated by BMP-4 in MC3T3-E1 cells.  Neither the BMP-4-induced phosphorylation of SMAD1/5/9 nor that of p38 MAPK affected by OSM. On the other hand, the BMP-4-stimulated phosphorylation of p70 S6 kinase was considerably suppressed by OSM. These results strongly suggest that OSM suppresses the BMP-4-stimulated OPG synthesis via inhibition of the p70 S6 kinase-mediated pathway in osteoblasts.

Abstract: A biomaterial is proposed for closing extensive bone defects in the maxillofacial region. The composition of the biomaterial includes high-molecular chitosan, chondroitin sulfate, hyaluronate, heparin, alginate and inorganic nanostructured hydroxyapatite. The purpose of the study is to demonstrate morphological and histological early signs of reconstruction of a bone cavity of critical size. The studies were carried out on 84 white female rats weighing 200-250 g. The study group consisted of 84 subjects in total, 40 in the experimental group and 44 in the control group. In all animals, three-walled bone defects measuring 0.5 x 04 x 05 cm were applied subperiosteally in the region of the angle of the lower jaw and filled in experimental group using lyophilized gel mass of chitosan-alginate-hydroxyapatite (CH-SA-HA). In control animals, the bone cavities were filled with an auto-blood clot after bone trepanation and bleeding. The observation periods are 3.5.7 days, 2.3.4.6.8 and 10 weeks. The control of bone regeneration was carried out using multiple morphological and histological analyses. Results showed that following implantation the chitosan construct actively replaced early-stage defects with the formation of a full-fledged new bone tissue as compared to the control group. Already, by the 7th day morphological analysis showed that formation of spongy bone tissue could be seen. After 2 weeks there was a pronounced increase in bone volume (P<0.01), and at 6 weeks after surgical intervention the closure of the defect was 70-80%, after 8 weeks - 100% without violation of bone morphology with a high degree of mineralization. Thus, the use of modified chitosan after filling eliminates bone defects of a critical size in the maxillofacial region, reveals early signs of bone regeneration, and serves as a promising material in reconstructive dentistry.

In the present study, the efficiency of a biomimetic approach by coating demineralized bone matrix (DBM) amorphous calcium phosphate (DBM+CaP), including its combination with serum albumin (DBM+CaP+BSA), was investigated. The intact structure of DBM promotes the transformation of amorphous calcium phosphate (CaP) into DPCD with a characteristic plate shape and particle size of 5–35 µm. The inclusion of BSA in the coating resulted in a better and more uniform distribution of CaP on the surface of DBM trabeculae. MG63 cells showed that both the obtained forms of CaP and its complex with BSA did not exhibit cytotoxicity up to a concentration of 10 mg/ml in vitro. Ectopic (subcutaneous) implantation in rats revealed pronounced biocompatibility, as well as strong osteoconductive, osteoinductive, and osteogenic effects for both DBM+CaP and DBM+CaP+BSA, but more pronounced effects for DBM+CaP+BSA. In addition, for the DBM+CaP+BSA samples, a pronounced full physiological intrafibrillar biomineralization and proangiogenic effect with the formation of bone-morrow-like niches, accompanied by pronounced processes of intramedullary hematopoiesis, indicating a powerful osteogenic effect of this composite have been achieved.

Maxillofacial fractures are a prevalent occurrence, and the widespread use of miniplates to stabilize and secure these fractures during surgery is common. However, the post-surgical fate of these miniplates remains a subject of contention among surgeons. Some advocate for their removal, while others suggest leaving them in place. This study aims to perform an extensive meta-analysis of pertinent studies to ascertain the destiny of miniplates employed in maxillofacial surgery and discuss the consequences of either their extraction or retention. To execute this meta-analysis, an exhaustive search was conducted across multiple databases, encompassing PubMed, Scopus, and Google Scholar. Keywords such as "titanium miniplates," "screws," "maxillofacial surgery," "complications," and "removal" were utilized to identify pertinent studies. The search was constrained to studies published between 1989 and 2022. The analysis encompassed only studies reporting outcomes related to miniplates in maxillofacial surgery, including complication rates and removal frequencies. Eleven studies conformed to the inclusion criteria and were incorporated into the meta-analysis, encompassing a total of 2240 patients. All the studies had a retrospective design, with the largest study involving 800 patients. The overall complication rate was determined to be 13.3%. The most prevalent reasons for miniplate removal included patient preference, tooth extraction, and infections. The average time span for miniplate removal was 10.7 months, with the most prolonged reported duration being 24 years. These findings imply that immediate removal might not be imperative in the majority of instances. In conclusion, our meta-analysis underscores the necessity of removing miniplates in cases where hardware leads to a variety of complications and physical discomfort. Principal factors driving plate removal included patient requests, tooth extractions, and infections. Ordinarily, plate removal took place within the span of 6 to 12 months, with the mandible being the most frequent site for removal. These findings accentuate the significance of extended monitoring to assess the trajectory of miniplates in maxillofacial surgery and provide valuable insights for future clinical decisions. To validate these conclusions and gain deeper insights into the factors influencing plate removal in maxillofacial surgery, further research with larger participant cohorts and standardized outcome reporting is imperative.

Different bone bruise patterns observed on magnetic resonance imaging (MRI) after non-contact anterior cruciate ligament (ACL) rupture and lateral patellar dislocation may indicate different injury mechanism of knee. In order to investigate the typical bone bruising patterns after ACL rupture and patellar dislocation. In this study, 77 ACL rupture and 77 patellar dislocation patients’ knee MR images with bone bruises between August 2020 and March 2022at our institution were selected and analyzed, respectively. Sagittal and transverse planes images were used to determine the bone bruise location in the lateral-medial and superior-inferior directions of the MR images. The presence, location, and intensity of the bone bruises within specific compartments of the femur and tibial after ACL rupture and patellar dislocation were recorded. Relative bone bruise patterns of the ACL rupture and patellar dislocation were classified and analyzed. Results showed that there were 4 kinds of bone bruise (1-,2-,3-,4- bone bruises) patterns after ACL rupture. The most common two patterns after ACL rupture were 3- bone bruises (including lateral side of femur and both lateral and medial side of tibia, LF+BT; both lateral and medial side of femur and lateral side of tibia, BF+LT, medial side of femur and both lateral and medial side of tibia, MF+BT) followed by 4- bone bruises (both lateral and medial side of femur and tibia, BF+BT), 2- bone bruises (LF+LT, lateral side of femur and tibia; MF+LT, medial side of femur and lateral side of tibia; LF+MT, lateral side of femur and medial side of tibia; MF+MT, medial side of femur and tibia; 0+BT, both lateral and medial side of tibia;), and 1- bone bruise (0+LT, only lateral side of tibia). There was only 1 pattern bone bruise (latera femur and medial patella bone bruise) of patellar dislocation, the most common pattern of patellar dislocation was in the inferior medial patella and lateral anterior inferior femur. The results suggest that the pattern of bone bruise after ACL rupture and patellar dislocation is completely different. There were 4 kinds of bone bruise patterns after non-contact ACL rupture while there was only 1 kind of bone bruise pattern after patellar dislocation bone bruise patients which was in the inferior medial patella and lateral anterior inferior femur.

There was no significant difference in bacterial adhesion between the 3 bone graft types tested, regardless of the bacterial strain used (p &gt; 0.22). After 72 hours of culture, there was no significant difference between the Fresh and Frozen bone groups, while the number of CFU in the Decellularised group was significantly lower (p &lt; 0.01), averaging -0.72 +/- 0.08 lg, -0.20 +/- 0.01 lg and -0.78 +/- 0.48 lg with S. epidermidis, S. aureus and E. coli respectively. Absolute values differences are low, and considering fresh bone (equivalent to autograft) as the gold standard due to its low infection rates in clinical studies, we can conclude that adhesion and biolfilm development characteristics are similar between Fresh, Frozen and Decellularised bone grafts..

HIV infection is well-known to be associated with the development of Hodgkin's lymphoma (HL) with extranodal involvement being exclusive bone marrow involvement is less common. Co-infection by other viruses such as the esptein Baar virus (EBV) increases the incidence of a frequent complication denominated hemophagocytic lymphohistocytosis (HLH). We present the case of a 50-year-old patient with the above clinical spectrum who develops several serious complications during treatment.

Shell nacre from Pinctada species has been extensively researched for managing bone defects. However, there is a gap in the research on using shell nacre as cement with improved physico-chemical properties. To address this, the current study aimed to develop a chemical curable com-posite shell nacre cement (SNC) using shell nacre powder and an organically modified ceramic resin shell nacre containing ladder-structured siloxane methacrylate (SNLSM). Different amounts of shell nacre (24, 48, and 72 weight(wt)%) were added to the SNLSM resin matrix and the effect on the physicochemical properties of the cement was studied. The composite shell nacre cement SNC 72 containing 72 wt% shell nacre exhibited significantly higher mechanical properties (com-pressive strength >100 MPa, flexural strength > 35 MPa) and low linear polymerization shrinkage (0.4%) than other compositions. SNC 72 was radiopaque and the exotherm generated during the curing of the cement was minimal. Direct contact of cured SNC 72 with L929 cells revealed the non-cytotoxic nature of the cement. Overall, the results of the study proved that the composite SNC 72 would be a promising candidate for bone defect management.

The gut microbiome is a collection of microorganisms and parasites that reside in the gastrointestinal tract. There are many factors that can affect the composition of this community, such as age, sex, medications, and environmental triggers. The relationship between the human host and the gut microbiota is very important for both the survival and development of the organism. The disruption of this relationship can lead to the development of various inflammatory diseases. CBD and THC are used to treat muscle spasticity associated with multiple sclerosis. It is now clear these compounds also benefit patients with neuroinflammation. A study that investigated the role of gut microbiota in treating the inflammation and paralysis in a mouse model demonstrated that treatment with CBD and THC produced significant decrease in the inflammation levels. They also exhibited a significant increase in the number of anti-inflammatory cytokines. The presence of certain cannabinoids can suppress neuroinflammation and prevent microbial dysbiosis. Several studies have revealed the role of the gut microbiota in the development and maintenance of skeletal integrity and bone mineral density. The gut is a major source of nutrients, including vitamins B and K. It can also influence the development and maintenance of bone matrix. The presence of the gut microbiota can influence the actions of certain T regulatory cells, which can lead to the development of bone formation and proliferation. In addition, its metabolites can prevent bone loss. The gut microbiota can help maintain the bone's equilibrium and prevent the development of metabolic diseases, such as osteoporosis. In this review, the dual functions gut microbiota plays in the regulation of gut-bone axis and gut-brain axis and the impact of CBD on these roles are discussed in detail.

This systematic review investigates the failure rate and marginal bone loss (MBL) of dental implants placed in Solid-organ transplant (SOT) patients compared to healthy controls. Three databases (PubMed, Web of Sciences and the Cochrane Library) were searched up to June 2020 (PROSPERO CRD42019124896). Case-control and cohort studies reporting data failure rate and marginal bone loss (MBL) of dental implants placed in SOT patients were included. The risk of bias of observational studies was assessed through the Newcastle-Ottawa Scale (NOS). Four case-control studies fulfilled the inclusion criteria, all of low risk of bias. Meta-analyses revealed consistently lower implant failure rate than control populations at patient and implant levels. SOT patients had a significant difference of -18% (p-value <0.001) of MLB towards healthy patients. SOT status poses no serious threat to implant survival. Overall, this group of patients presented lower levels of dental implant failure rate and marginal bone loss compared to otherwise healthy patients. Further intervention trials with wider sample size and longer follow-ups are necessary to confirm these summary results.

This study presents the development of a number of finite element (FE) models of the pelvis using different continuum and structural modelling approaches. Four FE models were developed using different modelling approaches: continuum isotropic, continuum orthotropic, hybrid isotropic and hybrid orthotropic. The models were subjected to an iterative adaptation process based on the Mechanostat principle. Each model was adapted to a number of common daily living activities (walking, stair ascent, stair descent, sit-to-stand and stand-to-sit) by applying onto it joint and muscle loads derived using a musculoskeletal modelling framework. The resulting models, along with a structural model previously developed by the authors, were compared visually in terms of bone architecture, and their response to a single load case was compared to a continuum FE model derived from CT imaging data. The main findings of this study were that the continuum orthotropic model was the closest to the CT derived model in terms of load response albeit having less total bone volume, suggesting that the role of material directionality in influencing the maximum orthotropic Young's modulus should be included in continuum bone adaptation models. In addition, the hybrid models, where trabecular and cortical bone were distinguished, had similar outcomes, suggesting that the approach to modelling trabecular bone is less influential when the cortex is modelled separately.

This study aimed to evaluate the physico-chemical properties, biocompatibility and bioabsorption of 3 different new membranes for bone guided regeneration (PLGA associated with hydroxyapatite and beta-TCP) with three thicknesses (200, 500 and 700 µm) implanted in mice subcutaneously. Scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and the quantification of Carbon, Hidrogen and Nitrogen were used to characterize the physico-chemical properties. One hundred Balb-C mice were divided into 5 experimental groups: Group 1 - Sham (without implantation); Group 2 - 200 μm; Group 3 - 500 μm; Group 4 - 700 μm; and Group 5 - Pratix®. Each group was subdivided into four experimental periods (7, 30, 60 and 90 days). Samples were collected and processed for histological and histomorphometrical evaluation. The membranes showed no moderate or severe tissue reactions in the experimental periods studied. The 500 μm membrane did not show tissue reaction for any experimental periods studied. The 200 μm membrane membranes began to exhibit fragmentation after 30- day, while the 500 and 700 µm membranes started the fragmentation at 90-day. All membranes studied were biocompatible, and the 500µm membrane showed the best results being a promissory membrane for bone guided regeneration.

Aims. Bone metastases have an incidence of up to 75% in metastatic breast cancer, thanks to the evolution of imaging we can identify them in the oligometastatic phase. With the introduction of target therapies and increasingly effective conjugated antibodies, it is increasingly common to treat patients with radiotherapy although asymptomatic (if single or ≤5 bone lesions). Volumes and doses in this setting do not yet have a clear guidelines. In this study, the aim is to administer to the macroscopically evident disease an ablative dose that favors the local control of disease. Aim of this retrospective analysis is to evaluate the outcome of pts receiving SIB for treatment of bone metastases. Material and Methods. A retrospective analysis including mBC patients (pts) undergone RT on bone metastases was conducted for pts treated between January 2014 and January 2022. Primary endpoint was freedom from local progression (FFLP). Rate of disease progression after radiotherapy (DP-AR) and overall survival (OS) were secondary endpoints. Subgroup analysis (age, immunophenotype, line of therapy) were performed. Results. Among 954 mBC who underwent radiotherapy for metastases, 85 pts underwent SIB-IMRT with a boost on macroscopic lesion of 8-6 Gy in 5 fr. Mean follow up was 41 months (6-61.5 m). Nineteen pts had single bone metastase (22.4%), 20 pts were oligometastatic (23,5%), 46 pts were plurimetastatic (54,1%). FFLP was 17 months (95% CI 3.2-61.5 m). Only 6 pts (7%) had local relapse on SIB-IMRT site during follow up. DP-AR was 13,2 m (95% CI 3.1-56.9 m). OS was 82,7 m (95% CI 10.6-343 m). Local-relapse was not associated with age, immunophenotype or sistemic line ongoing. Among secondary outcomes, DP-AR resulted associated to immunophenotype (p 0.002). DP-AR and OS were not significantly associated with local relapse (respectively p 0.148 and p 0.4). Conclusions. Pts with breast tumor can be treated with SIB-IMRT on bone metastases with a 93% of local control at 17 months from radiotherapy. Further data are needed to individuate pts who can benefit of dose-escalation and also sinergic effect with systemic therapies to possibly increase DP-AR.

The inclusion of exogenous phytase in broiler P and Ca deficient diets in response to heightened concerns over excessive P excretion into the environment over the years has remarkably been documented. However, responses among these studies have been inconsistent because of the several factors affecting P utilization. For this reason, a systematic review with meta-analysis of results from forty-one studies published from 2000 to February 2024 was evaluated to: 1) quantitatively summarize the size of phytase effect on growth performance, bone strength, and mineralization in broilers fed P and Ca deficient basal diets and 2) estimate and explore the heterogeneity of the effect sizes of outcomes using sub-group and meta-regression analyses. The quality of the included studies was assessed using the Cochrane Collaboration’s SYRCLE Risk of Bias checklists for animal studies. Additionally, applying the random-effects models, Hedges’ g effect size of supplementation with phytase was calculated using the R software to determine the standardized mean difference (SMD) at a 95% confidence interval. Sub-group analysis and meta-regression further explored heterogeneity (P_SMD ≤ 0.05, I² > 50%, n ≥ 10). The meta-analysis showed that supplemental phytase increases ADFI and BWG and reduces FCR at each time point of growth (< 0.0001). Additionally, phytase supplementation consistently increased tibia ash, P and Ca, and bone strength (< 0.0001) of broilers fed P and Ca deficient diets. Results of the subgroup and meta-regression analyses showed that age and strain of broiler, dietary P source, and duration of phytase exposure significantly influence the effect size of phytase on growth and bone parameters. In conclusion, phytase can attenuate the effect of reducing dietary available phosphorus and calcium and improve ADFI, BWG, and reduced FCR, especially when added to starter diets. It further enhances bone ash, bone mineralization, and bone-breaking strength of broilers, even though the effects of bone ash and strength can be maximized in the starter phase of growth. However, the effect sizes of phytase were related to the age and strain of the broiler, dietary P source, and duration of phytase exposure rather than the dosage.

Existing implants used with Total Knee Arthroplasty (TKA), Total Hip Arthroplasty (THA), and other joint reconstruction treatments, have displayed premature failures and frequent needs for revision surgery in recent years, particularly with young active patients who represent more than 55% of all joint reconstruction patients. Bone cement and stress shielding have been identified as the major reasons for premature joint failures. A breakdown of the cement may happen, and revision surgery may be needed because of the aseptic loosening. The significant mismatch of stiffness properties of patient trabecular bones and metallic implant materials in joint reconstruction surgery results in the stress shielding phenomenon. This could lead to significant bone resorption and increased risk of bone fracture and the aseptic loosening of implants. The present project introduces an approach for development of customized cellular structures to match the mechanical properties and architecture of human trabecular bone. It consists of four modules:1- characterization of geometry, microarchitecture, and stiffness properties of patient’s bones; 2- developing customized lattice structures tailored to mimic properties established in module 1; 3 - integration of developed lattice structure into full scale implant design and manufacturing; 4- implementation of the developed technology for use in implants that would overcome most of the issues related to aseptic loosening phenomenon. The present work aims at fulfilling the objectives of module 2 by exploring new designs of customized lattice structures and texture tailored to mimic closely patients’ bone anisotropic properties and that can incorporate an engineered biological press-fit fixation technique. The effects of various lattice design variables on mechanical performance of the structure are examined through systematic experimental plan using statistical design of experiments technique and analysis of variance method. All tested lattice designs were explored under realistic geometrical, biological, and manufacturing constraints. Of the four design factors examined in this study, strut thickness was found to have the highest percent contribution (41%) regarding the structure stiffness, followed by unit cell type, and cell size. Srut shape was found to have the lowest effect with only 11% contribution. The introduced solution offers lattice structure designs that can be adjusted to match bone stiffness distribution and promote bone ingrowth and hence eliminating the phenomenon of stress shielding while incorporating biological press-fit fixation technique.

Background: Assessing the impact of bone health clinical management in breast cancer (BC) patients receiving adjuvant endocrine therapy and designing a personalized clinical pathway to reduce bone loss, in an Italian research hospital. Methods: The primary endpoint was to assess (through the process improvement organizational method) the clinical pathway that post-surgical BC patients prescribed with endocrine therapy undergo to prevent bone loss. The secondary endpoint was to design a personalized clinical pathway for a prompt implementation of guidelines, to assess and possibly prescribe antiresorptive therapy. Results: During the first year of the new diagnostic therapeutic assistance pathway execution, an 60% increase in Dual-Energy X-ray Absorptiometry evaluations within 30 days and a 39.5% increase in antiresorptive therapy prescription within 90 days (since prescription of endocrine therapy) were shown, thus increasing patients’ compliance. Conclusion: Case managers and bone health specialists in this context can improve patients’ adherence to therapies and bone health, helping physicians to expand their collaboration.

Background: The COVID-19 pandemic has presented numerous challenges to global healthcare system and emerging evidence suggests a potential link between COVID-19 treatment, specifically steroid therapy, and the development of avascular necrosis (AVN) of the hip. This review aims to provide a comprehensive overview of recent studies and case reports investigating the relationship between COVID-19, corticosteroid therapy, and the development of AVN. Understanding the nuances of AVN in the context of COVID-19 is crucial for healthcare professionals to navigate treatment decisions and mitigate potential complications. Materials and Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was used in the systematic review until September 1st, 2023. The full-texts of the remaining twenty-three (n=23) articles were independently reviewed by the authors of this review.  Conclusions: The association between steroid therapy for COVID-19 and the development of hip AVN is a noteworthy concern even though, no relationship is evident between the duration of treatment, cumulative dosage of medication, maximum daily dosage received, and the presence of AVN. Further research with larger cohorts and long-term follow-up is needed to better understand the causative relationship and optimal management strategies for hip AVN in the context of COVID-19 and steroid therapy

Osteoporosis, often linked to increased osteoclast activity due to menopause or aging, was the focus. In this study, the inhibitory effects of Salicornia europaea L. (SE) water extract of desalted SE (WSE) were investigated on osteoclast differentiation and bone loss in ovariectomized mice. The findings revealed that WSE effectively inhibited RANKL-induced osteoclast differentiation, as evidenced by TRAP staining, and also suppressed bone resorption and F-actin ring formation in a dose-dependent manner. Gene expressions related to osteoclast differentiation, including NFATc1, TRAP, cathepsin K, and DC-STAMP, were downregulated by WSE. Oral administration of WSE improved bone density and structural parameters in ovariectomized mice. Dicaffeoyl quinic acids (DCQAs) and saponins in WSE were detected, with 3,4-, 3,5-, and 4,5-DCQA isolated and identified. All tested DCQAs, including the aforementioned types, inhibited osteoclast differentiation, bone resorption, and the expression of osteoclast-related genes. Furthermore, WSE and DCQAs reduced ROS production mediated by RANKL. These results indicate the potential of WSE and its components, DCQA, as preventive or therapeutic agents against osteoporosis and related conditions.

Insufficient oral ridge tissue presents a challenge in the treatment of dental implants. One method to enhance alveolar crest dimensions is guided bone regeneration (GBR); however, existing membranes have certain limitations. To address this issue, we aimed to compare the effectiveness of a resorbable bilayer membrane composed of poly(l-lactic acid) and poly(-caprolactone) （PLACL）with that of a collagen membrane（COL） in a rat GBR model. The rat calvaria was used as an experimental model by placing a plastic cylinder. Forty male Fisher rats underwent surgery, and micro-computed tomography and histomorphometric analyses were performed to assess bone regeneration. The results showed that bone regeneration was similar across all the groups. However, after 24 weeks, the PLACL membrane demonstrated significant resilience, occasional partial degradation, and intermittent air bubble formation. This extended preservation of the barrier effect has great potential to facilitate optimal bone regeneration. In conclusion, this study shows that the PLACL membrane is a promising alternative to GBR. By providing a durable barrier and supporting bone regeneration over an extended period, this resorbable bilayer membrane may address the limitations of the current membranes. Further studies and clinical trials are warranted to validate the efficacy and safety of this drug in humans.

In previous studies regarding the osseointegration of zirconia (ZrO2) implants, a lack of consistency was observed in the surface topographies of the ZrO2 and Ti samples because of the difficult processability of ZrO2 surfaces. To resolve this problem, we used the molecular precursor method (wet process), which is a surface-modifying technique that can easily change the surface chemistry without changing the surface topography. A roughened Ti surface was prepared using sandblasting (large-grit) and acid treatment. We were able to create ZrO2-coated Ti implants with the same topography as that of roughened Ti substrates using the molecular precursor method, which solution contained a Zr complex. The uniform presence of tetragonal Zr was confirmed, and the apparent zeta potential of the surface of the ZrO2-coated Ti implant was higher than that of Ti. In animal experiments, ZrO2-coated Ti implants showed an equivalent or higher bone-to-implant contact ratio compared to that of the non-coated implants inserted into the femur bone defects of the rats. ZrO2 with the same surface topography as that of roughened Ti exhibits a promotion of osteogenesis equivalent to or better than that of Ti in the early stages of bone formation.

Osteoporosis is a common metabolic bone disease in patients with diabetes, which can develop simultane-ously with Type 2 diabetes (T2D) in postmenopausal women. Bisphosphonate (BP) is administered to pa-tients with both the conditions and may cause medication-related osteonecrosis of the jaws (MRONJ). It affects the differentiation and function of osteoclasts as well as thickness of cortical bone through bone mineralization. Therefore, this study aimed to investigate the effects of T2D on osteoclast differentiation and activity as well as cortical bone formation in postmenopausal patients with MRONJ. Tissue samples were collected from 10 patients diagnosed with T2D and Stage III MRONJ in the experimental group and from 10 patients without T2D in the control group. Histological examination was conducted, and expres-sion of dendritic cell-specific transmembrane protein (DC-STAMP) and tartrate resistant acid phosphatase (TRAP) was assessed. Cortical bone formation was analyzed using CBCT images. The number of TRAP-positive osteoclasts and DC-STAMP-positive mononuclear cells were significantly less in the experi-mental group (p < 0.05). Furthermore, the thickness and ratio of cortical bone were significantly greater in the experimental group (p < 0.05). In conclusion, T2D decreased the differentiation and function of osteo-clasts, and increased cortical bone formation in postmenopausal patients with MRONJ.

Tissue engineering and regenerative medicine has gradually evolved as a promising therapeutic strategy to the modern healthcare of the aging and diseased population. In this study, we developed a novel nano-fibrous scaffold and verified its application in the critical bone defect regeneration. The metformin-incorporated nano-gelatin/hydroxyapatite fibers (NGF) was produced by electrospinning, cross-linked, and then characterized by XRD and FTIR. Cytotoxicity, cells adhesion, cell differentiation, and quantitative osteogenic gene and protein expression were analyzed by bone marrow stem cells from rat. Rat forearm critical bone defect model was performed for the in vivo study. The nano-gelatin/hydroxyapatite fibers (NGF) were characterized by their porous structures with proper interconnectivity without significant cytotoxic effects; the adhesion of bone marrow stem cells on the nano-gelatin/hydroxyapatite fibers (NGF) could be enhanced. The osteogenic gene and protein expression were upregulated. Post implantation, the new regenerated bone in bone defect was well demonstrated in the NGF samples. We demonstrated that the metformin-incorporated nano-gelatin-hydroxyapatite fibers greatly improved healing potential on the critical sized bone defect. Although metformin-incorporated nano-gelatin/hydroxyapatite fibers had advantageous effectiveness during bone regeneration, further validation is required before it can be applied to clinical applications.

A low calcium intake is associated with an increased fracture risk. We assessed the dietary calcium intake in a cohort of Italian individuals evaluated for low bone mineral density (BMD). A 7-day food-frequency questionnaire was administered to 1793 individuals consecutively referred at a Centre of the Italian Society for Osteoporosis, Mineral Metabolism and Skeletal Diseases for low BMD. In 30.3% (544/1793) and 20.9% (374/1793) of subjects the calcium intake was inadequate ( <700 mg/day) and adequate (>1200 mg/day), respectively. Patients with calcium intake <700 mg/day showed a higher prevalence of diabetes mellitus, idiopathic hypercalciuria and food allergy/intolerance (8.1%, 5.1%, 7.2%, respectively) than patients with calcium intake >700 mg/day (5.3%, 3.0%, 4.1%, respectively, p<0.04 for all comparisons), also after adjusting for age, gender and BMI. In 30.3% of fractured subjects the calcium intake was <700 mg/day. In Italy, a low calcium intake is highly prevalent in individuals at risk for low BMD. Importantly, an inadequate calcium intake is highly prevalent even in patients with history of fragility fractures. Only about a fifth of patients at risk for low BMD reported an adequate calcium intake

Dual energy X-ray absorptiometry (DEXA) measuring tool is a reliable and accurate technology to measure bone density and bone mineral composition. This research examined the composition and bone density (bone mineral composition and bone mineral density) of the whole body and representative body parts using DEXA. The participants were 240 healthy adult men and women who were divided into three groups based on age. The total bone mineral density (BMD) of women amounted to an average of 1.14 g/㎠ in Group A, 1.14 g/㎠ in Group B, and 0.98 g/㎠ in Group C. For men, the average BMD was 1.25 g/㎠ in Group A, 1.20 g/㎠ in Group B, and 1.17 g/㎠ in Group C. As a result, the reduction of age-specific BMD was shown to have a correlation with aging and body mass index(BMI), and it is determined that exercising on a regular basis can prevent reduction in BMD by maintaining appropriate muscle mass.

Tolerogenic dendritic cells are crucial to control development of autoreactive T cell responses and prevention of autoimmunity. We have reported that NOD.CD11cStat5b-CA transgenic mice expressing a constitutively active form of Stat5b under the control of CD11c promoter are protected from diabetes and that Stat5b-CA-expressing DCs are tolerogenic and halt ongoing diabetes in NOD mice. However, the molecular mechanisms by which Stat5b-CA modulates DC tolerogenic function is not fully understood. Here, we used bone marrow-derived DCs from NOD.CD11cStat5b-CA transgenic mice (Stat5b-CA.BMDC) and found that Stat5b-CA.BMDC displayed high levels of MHC class II, CD80, CD86, PD-L1 and PD-L2 and produced elevated amounts of TGFβ but low amounts of TNF and IL-23. Stat5b-CA.BMDCs upregulated Irf4 and downregulated Irf8 genes and protein expression and promoted CD11c+CD11b+ DC2 subset differentiation. Interestingly, we found that the histone methyltransferase Ezh2 interacted with Stat5b-CA complex that bound GAS sequences in the Irf8 enhancer whereas Ezh2 did not interact with GAS sequences in the case of the Irf4 promoter. Injection of Stat5b-CA.BMDCs to prediabetic NOD mice halted progression of islet inflammation and protected against diabetes. Importantly, inhibition of Ezh2 in tolerogenic Stat5b-CA.BMDCs reduced their ability to prevent diabetes development in NOD recipient mice. Taken together, our data suggest that the active form of Stat5b induces tolerogenic DC function by modulating IRF4 and IRF8 expression through recruitment of Ezh2 and highlight the fundamental role of Ezh2 in Stat5b-mediated induction of tolerogenic DCs function.

Biphasic bone substitutes (BBS) are nowadays established biomaterials. Through their constant development even natural components like hyaluronic acid (HY) are added to improve both their handling and also their regenerative properties. However, low knowledge exists regarding the consequences of the HY addition for their biocompatibility and the inflammatory tissue reactions. Thus, the present study was conducted aiming to analyze the influence of two different amounts of high molecular weight HY (HMWHY) combined with a BBS on the in vitro biocompatibility and the in vivo tissue reaction. Established in vitro procedures using L929 cells were used for cytocompatibility analyses under the test conditions of DIN EN:ISO 10993-5. For the in vivo study part, calvarial defects were created in 20 Wistar rats and subsequently filled with the BBS and the BBS combined with two different HMWHY amounts, i.e., BBS+HY(L) and BBS+HY(H). As controls empty defects were used. Established histological, immunohistochemical and histomorphometrical methods were applied to analyze the tissue reactions to the three different materials, including the induction of pro- and anti-inflammatory macrophages and multinucleated giant cells (BMGCs). The in vitro results showed that none of the materials or compositions caused biological damages to the L929 cells and can considered to be non-toxic. The in vivo results showed that only the addition of high doses of HY to a biphasic bone substitute significantly decreases the occurrence of proinflammatory macrophages (* p < 0.05) comparable to the numbers found in the control group, while no significant differences within the three study groups for M2-macrophages nor BMGCs were detected. In conclusion, the addition of different amounts of HMWHY does not seem to affect the inflammation response to the BBS while improving the material handling properties.

Purpose: The aim of the present experimental 3D-finite element study was to evaluate the influence of an augmented sinus lift with an additional inserted bone graft block. The bone graft block stabilizes the implant in addition to conventional augmented bone. We placed the block in three different positions. The implants were loaded with axial force and forces secondary to laterotrusion and protrusion. Material and Methods: A simplified U-shaped 3D finite element model of the upper jaw and a more complex anatomical model of the left maxilla were created. The bone graft block was placed in three positions: in the lower third in contact with the sinus floor, the middle, and the upper third of the implant. Van Mises’ stress distribution was calculated and analyzed for the different models. We also compared the complex anatomical model with the simplified one. Results: The position of the bone graft block significantly influences the magnitude of stress distribution. A bone graft block positioned in the upper third or middle of the implant reduces the quantity of stress compared to the reference model without a bone graft block. The low bone graft block position is clearly associated with lower stress distribution in compact bone. We registered no significant differences in stress in compact bone with regard to laterotrusion or protrusion. Conclusions: Maximum values of von Mises stresses in compact bone can be reduced significantly by using a bone graft block. The reduction of stress is nearly the same for positions in the upper third and the middle of the implant. It is much more pronounced when the bone graft block is in the lower third of the implant near the sinus floor, which appeared to be the best position in the present study.

As one of the typical deposits in Sichuan-Yunnan-Guizhou Pb-Zn metallogenic province, the Daliangzi Pb-Zn deposit has a close genetic relation with the structural system of “black/fracture zone” formed under the action of NWW-approx. EW strike-slip structures in the metallogenic province, but the mechanism of rock and ore-controlling action of the structural system remains unclear. Based on detailed analysis of tectonite-mineralized alteration lithofacies of R1 “black/fracture zone”, the tectonite-mineralized alteration lithofacies zones can be divided into 4 types in succession outward from the Pb-Zn mineralization center, i.e., ① brecciated and stockwork-like Pb-Zn mineralization-complex breccia facies zone, ② stockwork-like Pb-Zn mineralization-simple breccia and cataclasite facies zone, ③ veined pyrite-sulfide-dolomitic cataclasite facies zone, and ④ fine-veined calcite-black carbonized dolomite facies zone; Cl- and SO42--rich high-temperature oxidizing ore-bearing fluid mixes with reducing fluid in Zone ① while migration and precipitation occur in Zone ④. With the evolution of ore-forming fluid, the homogenization temperature decreases from Zone ① to Zone ④, the salinity increases from Zone ① to Zone ② and then decreases to Zones ③ and ④, and the fluid density has little change on the whole; the contents of Zn, Pb, Cu, Ga, Ge, Cd, Ag, and other metallogenic elements, the Zn/Pb ratio, and the CaO/MgO mole ratio decrease gradually from Zone ① to Zone ④; and REE fractionation, calcilization, silicification, and pyritization enhance gradually from Zone ① to Zone ④. This series of changes are the product of diapirism (cryptoexplosion) of strike-slip structures and “black/fracture zone”, among which the second-order structures (F5, F100, and other faults) derived from NWW-approx. EW striking dextral shear-tension faults F1 and F15 control the brecciated and stockwork-like Pb-Zn mineralized complex breccia facies zones and the stockwork-like Pb-Zn mineralized simple breccia and cataclasite facies zones. Therefore, this paper establishes the zoning mode of tectonite-mineralized alteration lithofacies of “black/fracture zone” and proposes that Zones ① and ② are important prospecting criteria. conclusions.

Aluminum wire is a common material for wire bonding due to its resistance to oxidation and low price. It does not melt when becoming a free air ball (FAB) during the electronic flame-off (EFO) process with wettability, and is applied by wedge bonding. This study used 20μm Zn-Coated Al-0.5wt.%Si (ZAS) wires to improve the FAB shape after the EFO process, while maintaining stability of the mechanical properties, including the interface bonding strength and hardness. In order to test circuit stability after ball bonding, the current-tensile test was performed. During the experiment, it was found that 80nm ZAS with wire bonding has lower resistance and higher fusing current. For the bias tensile test, the thicker Zn film diffused into the Al-Si matrix easily, after which the strength was reduced. The ball-bond interfaces had no change in their condition before and after the bias. Accordingly, ZAS could be a promising candidate for ball bonding in the future.

Some evidence supports the influence of the implant macro-design and primary stability. Additionally, tactile perception can be used to assess implant stability when placing the implant. This research aimed to quantify the primary and secondary stability of three implant systems with two different macro geometries (cylindrical and conical) determined through the insertion torque and the implant stability quotient (ISQ) at the moment of implant placement as a function of implant-related factors (length, width, dental arch, and implant location in the arch), intraoperative factors (bone density determined subjectively by the clinician's tactile perception), and patient-related factors (age, gender and bone density determined objectively in the cone beam computed tomography (CBCT). Methods: 102 implants of three implant systems with two different macro geometries (conical and cylindrical) were placed in 53 patients. The insertion torque, the ISQ at the implant placement (ISQ0), and bone quality according to the clinician's tactile sensation were recorded on the day of the surgery. After a three-month healing period, the ISQ was re-evaluated (ISQ3). Results: Cylindrical implants exhibited significantly higher insertion torque and ISQ at the moment of the surgery and after three months than conical implants. Cylindrical implants also showed significantly lower indices of tactile evaluation of bone quality during the implant placement surgery. However, no differences were demonstrated in the bone density measured objectively in the CBCT. (4) Conclusions: The cylindrical implants achieved the highest values for primary stability (Ncm and ISQ) and secondary stability (ISQ after three months). Insertion torque was the variable that most influenced ISQ on the day of the surgery. Implant location (incisors-canines, bicuspids-molars) and the implant macro geometry were the variables that most influenced the secondary stability (ISQ at three months).

After peripheral nerve injury, axon and myelin regeneration are key events for optimal clinical improvements. We have previously shown that early bone marrow mononuclear cell (BMMC) transplantation exerts beneficial effects on myelin regeneration. In the present study we analyze whether there is a temporal window in which BMMC migrate more efficiently to damaged nerves while still retaining their positive effects. Adult Wistar rats of both sexes, with sciatic nerve crush were systemically transplanted with BMMC at different days post injury. Vehicle-treated, naïve, and sham rats were also included. Morphological, functional, and behavioral analyses were performed in nerves from each experimental group at different survival times. BMMC transplantation between 0 and 7 days after injury resulted in the largest number of nested cells within the injured sciatic nerve, which supports the therapeutic value of BMMC administration within the first week after injury. Most importantly, later BMMC administration 7 days after sciatic nerve crush was associated with neuropathic pain reversion, improved morphological appearance of the damaged nerves, and a tendency toward faster recovery in the sciatic functional index and electrophysiological parameters. Our results thus support the notion that even delayed BMMC treatment may represent a promising therapeutic strategy for peripheral nerve injuries.

Osteoporosis is considered a serious public health problem, particularly affecting the postmenopausal period. In 2018, in the Republic of Kazakhstan the total and primary incidence was 10 and 3.7 cases per 100,000 adults, respectively. The objective is to study osteoporosis prevalence and indicate main factors affecting low bone mineral density by screening adult population of Abay region, Kazakhstan. The target group were 641 respondents aged between 18 and 65 years old, Kazakh population living in Abay region since birth. All participants filled out questionnaire and had a bone mineral density measurement by dual energy X-ray absorptiometry (DXA) between July 15, 2023 and February 29, 2024. Logistic regression analysis was conducted to assess the association between low bone mineral density and key demographic characteristics, aforementioned lifestyle factors and nutrition habits. We identified the prevalence of low bone density and osteoporosis at the level of 34.1% with the highest prevalence in the older population group (50+ years) - 48.3%. Regression analysis revealed a number of indicators associated with the likelihood of bone sparing. However, only 4 of these showed significance in the final multivariate model (R2=22.4%). These included age (AOR 1.05), body mass index (AOR 0.92), fracture history (AOR 1.64), consumption of nuts and dried fruits were associated with lower prevalence of osteoporosis (AOR 0.48). Our study was the first in Kazakhstan that investigates the association of key demographic, behavior and anamnestic factors with low mineral density.

This study aimed to demonstrate the potential role of Dual Energy CT in assessing Bone Mineral Density (BMD) in postmenopausal women. A retrospective study was conducted on 51 postmenopausal female patients who underwent DXA and DECT examinations for other clinical reasons. DECT images were acquired with spectral imaging using a 256-slice system. These images were processed and visualized using an HAP(fat) map. Statistical analysis was performed using the Bland-Altman method to assess agreement between DXA and DECT HAP(fat) measurements. Mean BMD, vertebral and femoral T-scores were obtained. For vertebral analysis, the Bland-Altman plot showed an inverse correlation (R2: -0.042; RMSE: 0.690) between T-scores and DECT HAP(fat) values for measurements from L1 to L4, while a good linear correlation (R2: 0.341; RMSE: 0.589) it was found for measurements at the femoral neck. In conclusion, we demonstrated the enhanced accuracy of BMD calculation through DECT, finding a statistically significant correlation only at the femoral neck where BMD results do not seem to be influenced by the overlap of the measurements on cortical and trabecular bone. This outcome could be beneficial in the future by reducing radiation exposure for patients already undergoing follow-up for chronic conditions.

Our previous study demonstrated that mesenchymal stem/stromal cells (MSCs) induced the differentiation of myeloid-derived suppressor cells (MDSCs) in the bone marrow (BM) under inflammatory conditions. In the present study, we aimed to explore the signaling pathway in BM cells responsible for MDSC generation. RNA-seq revealed that the mitogen-activated protein kinase (MAPK) pathways, among biochemical pathways, exhibited the highest number of differentially expressed genes in BM cells with MSC coculture relative to those without. Western blot confirmed strong phosphorylation of c-Jun N-terminal kinase (JNK) in BM cells cocultured with MSCs under GM-CSF stimulation, whereas p38 kinase activation remained unaltered by MSCs. Inhibition of JNK by SP600125 significantly abolished the expression of Arg1 and Nos2, the hallmark genes of MDSCs, as well as Hif1α, a molecule mediating monocyte functional re-programming into suppressive phenotype, in MSC-cocultured BM cells, while increasing TNF-α in response to lipopolysaccharides stimulation. Furthermore, JNK inhibition markedly abrogated the effect of MSCs on the production of TGF-β1, TGF-β2 and IL-10 in BM cells. These results suggest that MSCs induce MDSC differentiation in BM during inflammation, at least in part, through the activation of the JNK MAPK signaling pathway.

Background: Antibiofilm activity of silver nanoparticles has been extensively investigated in common bacteria. Metallo-β-lactamase producing Gram-negative bacteria are hard-to-treat microorganisms with few therapeutic options, and silver nanoparticles were not evaluated on the biofilm of these bacteria. Objectives: The aim of this study was to evaluate the antibiofilm activity of a bone scaffold impregnated with silver nanoparticles in NDM-producing Gram-negative bacilli. Methods: Bone scaffolds from bovine femur were used for the tests and impregnated with silver nanoparticles (50 nm) by physical adsorption. Silver nitrate minimal inhibitory and bactericidal concentrations (MIC and MBC) were performed on NDM-producing Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Disc diffusion tests for silver nanoparticles susceptibility and quantification of biofilm production on plate and bone with sessile cell count were performed. Results: The MIC results demonstrated that silver nitrate had an antimicrobial effect on all microorganisms, inactivating the growth of isolates from a concentration of 8 µg/mL. MBC results showed that E. coli 16.211 was the only isolate to present MIC different from MBC, with a value of 16 µg/mL. Conclusion: Bone scaffolds impregnated with silver nanoparticles can significantly reduce biofilm, and it can be a strategic material to be used as an implant for different approaches.

Large volume bone defect regeneration is complex and demands time to complete. Several regeneration phases with unique characteristics including immune responses follow, overlap, and interdepend on each other and, if successful, lead to the regeneration of the organ bone's form and function. However, during traumatic, infectious, or neoplastic clinical cases, the intrinsic bone regeneration capacity may exceed, and surgical intervention is indicated. Scaffold-guided bone regeneration (SGBR) has recently shown efficacy in preclinical and clinical studies. To investigate different SGBR strategies over periods of up to 3 years we have established a well characterized large segmental tibial bone defect ovine model, for which we have developed and optimized immunohistochemistry (IHC) protocols. We present an overview of the immunohistochemical characterization of different experimental groups in which all ovine segmental defects were treated with a bone grafting technique combined with a three-dimensionally printed medical-grade polycaprolactone-tricalcium phosphate (mPCL-TCP) scaffold. The qualitative data set is based on osteoimmunological findings gained from IHC analyses of over &gt;350 sheep surgeries over the past two decades. Our systematic and standardized IHC protocols enabled us to gain further insight into the complex and long-drawn-out bone regeneration processes, which ultimately proved to be a critical element for successful translational research.

Bone marrow mononuclear cells (BMMNCs) have emerged as a potential therapeutic strategy for various incurable conditions including autism spectrum disorder (ASD). To study its safety and efficacy, we analyzed 1011 patients who underwent intrathecal administration of autologous BMMNCs along with neurorehabilitation. At mean follow-up of 19.3 months after intervention, 90.6% patients showed overall improvement. Improvements were observed in attention concentration, command following, eye contact, sitting tolerance, social interaction, hyperactivity, communication, speech, aggressiveness, stereotypical and self-injurious behavior. Statistically significant changes were observed in scores of Indian Scale of Autism Assessment and Childhood Autism Rating Scale (p<0.05). On subgroup analysis, improvements were recorded irrespective of age and disease severity and better outcome was observed in patients who took multiple doses of cell therapy compared to single dose. Comparative Brain PET-CT scan of 401 patients showed improved brain metabolism after the intervention. No major adverse events were reported. Only 9 out of 1011 patients experienced seizures which were managed using medications. 4 out of 9 had history of seizures while 5 had normal EEG with no history. However, improvements were still observed in these 9 patients. Thus, intrathecal transplantation of autologous BMMNCs along with neurorehabilitation is safe and efficacious in patients with ASD.

Quantification of bone loss for follow-up comparisons has not been routinely performed in patients with parietal thinning so far. This study compares different methodological approaches including both 2- and 3-dimensional methods in computerized tomographies of a single patient. The 2-dimensional method provides accurate measurements of bone thickness, while the 3-dimensional method allows for a more comprehensive view of the bone's structure, including parameters like shape, size, and thickness. The techniques provided valuable data for the treating physician and suggest a possible effect of corticosteroids in this individual patient. The study concludes that 3-dimensional reconstruction of computerized tomographies with subsequent 2-dimensional analyses appears justified for routine radiological practice to increase clinical awareness of the size of the parietal bone defects and allow for quantification of bone loss during long-term follow-ups. Further validation of the proposed analytical approaches is warranted in larger studies to investigate patterns of bone thinning across the skull and changes in bone volumes over time, with specialized software to be approved for such analyses.

Background: Initial phases of molecular and cellular maladaptive bone response at early CKD remain mostly unknown. Methods: We induced mild CKD in SHRs by either arterial hypertension lasting six months (sham-operated rats, SO6) or in its’ combination with 3/4 nephrectomy lasting two and six months (Nx2 and Nx6, correspondently). Sham operated SHRs (SO2) and Wistar Kyoto rats (WKY2) with two-month follow-up served as controls. Animals were fed standard chow containing 0.6% phosphate. We measured creatinine clearance, urine albumin-to-creatinine ratio, renal interstitial fibrosis, inorganic phosphate (Pi) exchange, intact PTH and FGF23, Klotho, dickkopf-1, sclerostin. And assessed bone response by static histomorphometric indices and gene expression profiles. Results: Mild CKD groups had no increase in renal Pi excretion, FGF23 and PTH levels. Serum Pi, dickkopf-1, and sclerostin were higher in Nx6. Decrease in trabecular bone area and osteocyte number was obvious in SO6. Nx2 and Nx6 had additionally lower osteoblast number. The decline in eroded perimeter was only apparent in Nx6. Significant downregulation of genes related to Pi transport, MAPK, WNT, and BMP signaling accompanied histological alterations in Nx2 and Nx6. Conclusions: We found an association of mild CKD with histological and molecular features suggesting lower bone turnover, which occurred at normal levels of systemic Pi-regulating factors.

Malnutrition is one of major factors of bone and cartilage disorders. Pacific cod (Gadus macrocephalus) processing waste is a cheap and highly promising source of bioactive substances, including collagen-derived peptides and amino acids, for bone and cartilage structure stabilization. Addition of these substances to a functional drink is one of the ways to achieve their fast intestinal absorption. Collagen hydrolysate was obtained via enzymatic hydrolysis, ultrafiltration, freeze-drying, and grinding to powder. The lyophilized hydrolysate was a light gray powder with high protein content (>90%), including collagen (about 85% of total protein) and a complete set of essential and non-essential amino acids. The hydrolysate was applicable as a protein food supply or a structure-forming food component due to presence of collagen fiber fragments. An isotonic fitness drink (osmolality 298.1 ± 2.1 mOsm/L) containing the hydrolysate and vitamin C as a cofactor in collagen biosynthesis was prepared. Addition of the hydrolysate did not adversely affect its organoleptic parameters. Production of such functional foods and drinks is one of the beneficial ways of fish processing waste utilization.

The nature of bone homeostasis is the coordination between the osteoblasts (OBs) and osteoclasts (OCs). However, abnormal activation of osteoclasts (OCs) could compromise the bone homeostasis. Thus, it is imperatively urgent to explore effective medical interventions for patients. NO/guanylate cyclase (GC)/cGMP signaling cascade has been widely reported in regulating bone metabolism, and GC plays a significantly critical role. Vericiguat, a novel oral soluble guanylate cyclase (sGC) stimulator, has been firstly reported in 2020 to treat patients with heart failure. However, the effect of Vericiguat on the function of OCs has not been explored. In this present study, we found that the concentration range of Vericiguat between 0-8uM was none- cytotoxic to BMMs. Vericiguat could enhance differentiation of OCs at concentration of 500nM, whereas it inhibited differentiation at 8 uM in terms of the number and size of OCs. In addition, Veirciguat also showed dural effect on RANKL‐induced OC fusion and bone resorption in a concentration‐dependent manner. Further, molecular assay suggested that the dually regulatory effect of Vericiguat on OCs was mediated by the bidirectional activation of IκB-α/NF-κB signaling pathway. Taken together, our present study demonstrated the dual effects of Vericiguat on the formation of functional OCs in a concentration-dependent manner. The regulatory effect of Vericiguat on OCs was mediated by the bidirectional activation of IκB-α/ NF-κB signaling pathway, and a potential balance between IκB-α/ NF-κB signaling pathway and sGC/cGMP/VASP may exist.

Subchondral bone loss is an important pathological feature of early-stage temporomandibular joint (TMJ) osteoarthritis (OA). Previous studies focused mainly on the bone resorption by osteoclasts in early-stage OA, but the bone formation feature has not drawn enough attention. Sema4D/Plexin-B1 is a pair of molecules expressed by osteoclast/osteoblast, which is capable of inhibiting bone formation by osteoblasts. The present study found that subchondral bone loss in early-stage TMJ OA was accompanied by up-regulated expression of Sema4D in cartilage and subchondral bone and Plexin-B1 in subchondral bone. Reducing Sema4D level could inhibit the subchondral bone loss and cartilage degeneration of early-stage TMJ OA. In vitro, results revealed that Sema4D could reduce the expression of osteocalcin (OCN) and alkaline phosphatase (ALP), and increase the migrating capability of Plexin-B1-positive osteoblasts. Our results revealed that elevated Sema4D expression in early-stage TMJ OA might decrease the bone formation activity of osteoblasts in the subchondral bone by binding to Plexin-B1 expressed by osteoblasts. Inhibiting Sema4D/Plexin-B1 signaling in the early-stage OA holds promise as a strategy for new therapeutic approaches to osteoarthritis.

Bioactive glass (BG) represents a promising biomaterial for bone healing; here injectable BG pastes biological properties were improved by 25 wt% gelatin or chitosan, as well as mechanical resistance was enhanced by adding 10 or 20 wt% 3-Glycidyloxypropyl trimethoxysilane (GPTMS) cross-linker. Composites exhibited bioactivity as apatite formation was observed by SEM and XRD after 14 days immersion in SBF; moreover, polymers did not enhance degradability as weight loss was &gt;10% after 30 days in physiological conditions. BG-gelatin-20 wt% GPTMS composites demonstrated the highest compressive strength (4.8±0.5 MPa) in comparison with 100% BG control (1.9±0.1 MPa). Cytocompatibility was demonstrated towards human mesenchymal stem cells (hMSC), osteoblasts progenitors and endothelial cells. The presence of 20 wt% GPTMS conferred antibacterial properties thus inhibiting the joint pathogens Staphylococcus aureus and Staphylococcus epidermidis infection. Finally, hMSC osteogenesis was successfully supported in a 3D model as demonstrated by alkaline phosphatase release and osteogenic genes expression.

Bone marrow-derived mesenchymal stem cells (BMSCs) have been considered a promising therapeutic approach to cardiovascular disease. This study intends to compare the effect of BMSCs through a standard active cardiac support device (ASD) and intravenous injection on global myocardial injury induced by isoproterenol. BMSCs were cultured in vitro, and the transplanted cells were labeled with a fluorescent dye CM-Dil. Isoproterenol (ISO) was injected into the rats; two weeks later, the labeled cells were transplanted into ISO-induced heart-injury rats through the tail vein or ASD device for five days. The rats were sacrificed on the first day, the third day, and the fifth day after transplantation to observe the distribution of cells in the myocardium by fluorescence microscopy. The hemodynamic indexes of the left ventricle were measured before sacrificing. H&E staining and Masson’s trichrome staining were used to evaluate the cardiac histopathology. In the ASD groups, after three days of transplantation, there were many BMSCs on the epicardial surface, and after five days of transplantation, BMSCs were widely distributed in the ventricular muscle. But in the intravenous injection group, there were no labeled-BMSCs distributed. In the ASD+BMSCs-three days treated group and ASD+BMSCs -five days-treated group, left ventricular systolic pressure (LVSP), the maximum rate of left ventricular pressure rise (+dP/dt), the maximum rate of left ventricular pressure decline (-dP/dt) increased compared with model group and intravenous injection group (P<0.05). By giving BMSCs through ASD device, cells can rapidly and widely distribute in the myocardium and significantly improve heart function.

Background: The aim of the present investigation was to evaluate the clinical success of horizontal ridge augmentation in the severely atrophic maxilla (Cawood and Howell class IV) using freeze-dried custom made bone harvested from cadaver donors tibial hemiplateau and to analyze the marginal bone level gain prior dental implants placement at 9 months after bone grafting and before prosthetic rehabilitation. Methods: A 52-year-old woman received custom made bone grafts. Patient underwent CT scans 2 weeks prior and 9 months after surgery for graft volume and density analysis. Results: The clinical and radiographic bone observations showed a very low rate of resorption after bone graft and implant placement. Conclusions: The custom-made allograft material was a highly effective modality for restoring the alveolar horizontal ridge, resulting in this way to reduce the need to obtain autogenous bone from a secondary site with predictable procedure. Further studies are needed to investigate its behavior at longer time points.

One-dimensional nanostructures such as silver nanowires (AgNWs) have attracted considerable attention owing to their outstanding electrical, thermal and antimicrobial properties; however, their application in the prevention of infections linked to bone tissue regeneration interventions has not yet been explored. Here we report on the development of an innovative scaffold prepared from chitosan, composite hydroxyapatite and AgNWs (CS-HACS-AgNWs) having both bioactive and antibacterial properties. In vitro results highlighted the antibacterial potential of AgNWs against both gram-positive and gram-negative bacteria. The CS-HACS-AgNWs composite scaffold demonstrated suitable Ca/P deposition, improved gel strength, reduced gelation time, and sustained Ag+ release within therapeutic concentrations. Antibacterial studies showed that the composite formulation was capable of inhibiting bacterial growth in suspension and of completely preventing biofilm formation on the scaffold in the presence of resistant strains. The hydrogels were also shown to be biocompatible, allowing cell proliferation. In summary, the developed CS-HACS-AgNWs composite hydrogels demonstrated significant potential as a scaffold material to be employed in bone regenerative medicine, as it presents enhanced mechanical strength combined with the ability to allow calcium salts deposition, while efficiently decreasing the risk of infections. The results presented justify further investigations into potential clinical applications of these materials.

The number of patients with bone metabolic disorders including osteoporosis is increasing worldwide. These disorders often facilitate bone fractures, which seriously impact the patient’s quality of life and could lead to further health complications. Bone homeostasis is tightly regulated to balance bone resorption and formation. However, many anti-osteoporotic agents are broadly categorized as either bone forming or anti-resorptive, and their therapeutic use is often limited due to unwanted side effects. Therefore, safe and effective therapeutic agents are needed for osteoporosis. This study aims to clarify the bone protecting effects of oat bran water extract (OBWE) and its mode of action. OBWE inhibited RANKL-induced osteoclast differentiation by blocking c-Fos/NFATc1 through the alteration of I-κB. Furthermore, we found that OBWE enhanced BMP-2-stimulated osteoblast differentiation by the induction of Runx2 via Smad signaling molecules. In addition, the anti-osteoporotic activity of OBWE was also evaluated using an in vivo model. OBWE significantly restored ovariectomy-induced bone loss. These in vitro and in vivo results showed that OBWE has the potential to combat bone metabolic disorders including osteoporosis

In this study, four kinds of animal bone marrow powders were extracted with n-hexane using the Soxhlet extraction method. Polyunsaturated fatty acids were enriched by urea inclusion and low temperature crystallization method, then were further evaluated antioxidant and antibacterial activities. These results showed that the oil composition of the n-hexane extracts of four kinds of animal bone marrow primarily consisted of palmitic acid (18.57–31.01%), stearic acid (3.6–20.95%), and oleic acid (40.22–58.69%). The ratios of saturated fatty acids (SFA)/unsaturated fatty acids (UFA) were 1/1.417, 1/1.327, 1/2.140, and 1.285/1 for sheep, bovine, horse, and camel bone marrow oil, respectively. The SFA/UFA ratios determined by the urea inclusion method were 1/1.518, 1/1.390, 1/2.037, and 1.216/1, respectively. The SFA/UFA ratios according to the low temperature crystallization method with acetone were 1/1.920, 1/2.141, 1/2.360, and 1/1.157 for sheep, bovine, horse, and camel bone marrow oil, respectively. These enrichment methods effected the concentrations of UFAs from the camel bone marrow oil. Among the methods, the low temperature crystallization method effectively enriched the UFAs. All four bone marrow oils exhibited strong antioxidant and antimicrobial activities. The horse bone marrow oil showed the strongest antioxidant activity. Both antioxidant and antimicrobial activity improved after enrichment of the UFAs. These results lay a theoretical basis for application bone marrow oil resources in food and medicine.

Masquelet induced-membrane technique for the treatment of segmental bone defects includes a two-stage surgical procedure, and polymethylmethacrylate (PMMA) plays a major role in the treatment. However, the PMMA spacer must be surgically removed. Here, we investigated the potential of poly (lactic-co-glycolic acid) (PLGA) nanofibers, a biodegradable material to replace PMMA spacer, allowing the bioactive membrane to be induced, and the spacer to degrade without the additional surgery on a rabbit femoral segmental bone defect model. PLGA nanofibers were shown to degrade completely six weeks after implantation in the investigated animals, and a thick membrane was found to circumferentially fold around the segmental bone defects. Results from image studies demonstrated that, in the group without bone graft, all studied femurs exhibited either nonunion or considerable malunion. In contrast, the femurs in the bone graft group had a high union rate without considerable deformities. Histological examinations suggested that the membranous tissue in this group was rich in small blood vessels and the expression of BMP2 and VEGF increased. Our results demonstrate that the biodegradable PLGA nanofibers may be useful for replacing the PMMA spacer as the bioactive-membrane inducer, facilitating the process of healing and removing the need for repeated surgeries.

Abstract A variety of surgical techniques have been developed to reconstruct the posterior maxilla when bone volume is insufficient. A barrier membrane or bone window pushed inside the sinus cavity as the ‘‘roof’’ of the sinus cavity for preserve the space and help bone. The heterologous cortical lamina is used for the mechanical support, without any grafting material, of sinus membranes resulting in only bone tissue formation and not mixed with the graft.

The purpose of this study was to evaluate the bioactivity and cell response of a well-characterized Nurse´s A-phase (7CaO•P2O5•2SiO2) ceramic and his effect compared to a control (tissue culture polystyrene-TCPS) on the adhesion, viability, proliferation and osteogenic differentiation of ahMSCs in vitro. Cell proliferation (Alamar Blue Assay), Alizarin Red-S (AR-s) staining, alkaline phosphatase (ALP) activity, osteocalcin (OCN) and collagen I (Col I) were evaluated. Also, field emission scanning electron microscopy (FESEM) images were acquired in order to visualise the cells and the topography of the material. The proliferation of cells growing in a direct contact with the material was slower at early stages of the study because of the new environmental conditions. However, the entire surface was colonized after 28 days of culture in growth medium (GM). Osteoblastic differentiation markers were significantly enhanced in cells growing on Nurse´s A phase ceramic and cultured with osteogenic medium (OM), probably due to the role of silica to stimulate the differentiation of ahMSCs. Moreover, calcium nodules were formed under the influence of ceramic material. Therefore, it is predicted that Nurse´s A-phase ceramic would present high biocompatibility and osteoinductive properties being a good candidate to be used as a biomaterial for bone tissue engineering.

Based on the engineering background of Daliuta mining area, the fracture distribution and water movement within the weakly cemented overlay strata are studied through liquid-solid coupling physical simulation and COMSOL numerical simulation test. 3D fracture network of overburden strata in mining is plotted based on the result of the physical simulation test. The results showed that the ‘fractured zone’ of the weakly cemented overburden strata in the western area develops more evidently than that in the eastern area ---- wide-opened fractures form at both ends of the working area and this leads to a wide distribution of fractures in the overlying strata.After the initial caving of the roof, height of the penetrating fractures increases rapidly and the separated strata space becomes the main channel for water flow. Under the action of water flow and rock strata movement, mining-induced fractures in overlying rock display cyclic change of expansion, penetration and closure. When the working face is fully mined, the penetrating fractures in the overlying strata and mining-induced fractures up in the working face become the main passages for water flow. The experimental result provides a reference for underground reservoirs layout and maintenance and water-conserved mining in western China.