Purpose: to assess any differences on marginal bone loss between bone-level or tissue-level dental implants through a review of literature until September 2019. Materials and methods: MEDLINE, Embase and other database were searched by two independent authors. The search was limited to articles in English. Results: The search provided 1028 records and, after removing the duplicates through titles and abstracts screening, 45 full-text articles were assessed for eligibility. For qualitative analysis 20 articles were included, 17 articles of them for quantitative analysis. A total of 1161 patients (mean age 54,4 years) and 2933 implants were observed, 1427 (Tissue-level) and 1506 (Bone-level). The survival rate and the success rate were more than 90%, except for 2 studies with a success rate of 88% and 86.2%. No studies reported any differences between groups in term of success and survival rates. Three studies showed that BL-implants had statistically less marginal bone loss (P< 0.05). Only one study reported statistically less marginal bone loss in TL-implants (P< 0.05). In the most part of the studies, differences between implant types in marginal bone loss were not statistically significant. Conclusion: Despite to the peri-implant tissue around transmucosal implants has been reported to be inflammation-free because of the absence of bacterial infiltration in the micro-gap between the fixture and abutment, no clinical and radiological differences were highlighted between groups from the included studies after a variable period of follow-up ranged between 1 to 5 years.

The recent approval of 177Lu PSMA-617 (Pluvicto®) by the United States Food and Drug Administration (FDA) is the culmination of decades of work in advancing the field of targeted radionuclide therapy for metastatic prostate cancer. 177Lu PSMA-617, along with the bone specific radiotherapeutic agent, 223RaCl2, are now commonly used in routine clinical care as a tertiary line of therapy for men with metastatic castrate resistant prostate cancer and for osseus metastatic disease respectively. While these radiopharmaceuticals are changing how metastatic prostate cancer is classified and treated, there is relatively little guidance to the practitioner and patient as to how best utilize these therapies, especially in conjunction with other more well-established regimens including hormonal, immunologic, and chemotherapeutic agents. This review article will go into detail about the mechanism and effectiveness of these radiopharmaceuticals and less well known classes of targeted radionuclide radiopharmaceuticals including alpha emitting prostate specific membrane antigen (PSMA) -, gastrin-releasing peptide receptor (GRPR) -, and somatostatin targeted radionuclide therapeutics. Additionally, a thorough discussion of the clinical approach of these agents is included and required futures studies.

Abstract: Fanconi anemia (FA), a chromosomal instability syndrome, is caused by inherited pathogenic variants in any of 22 FANC genes, that cooperate in the FA/BRCA pathway. This pathway regulates the repair of DNA interstrand crosslinks (ICLs) through homologous recombination. In FA proper repair of ICLs is impaired, and accumulation of toxic DNA double strand breaks occurs. In order to repair this type of DNA damage, FA cells activate alternative error-prone DNA repair pathways, that may lead to the formation of gross structural chromosome aberrations of which radial figures are the hallmark of FA and their segregation during cell division are the origin of subsequent aberrations like translocations, dicentrics and acentric fragments. The deficiency in DNA repair has pleiotropic consequences in the phenotype of patients with FA, including developmental alterations, bone marrow failure and an extreme risk to develop cancer. The mechanisms leading to the physical abnormalities during embryonic development have not been clearly elucidated, however FA has features of premature aging with chronic inflammation mediated by pro-inflammatory cytokines, that results in tissue attrition, selection of malignant clones and cancer onset. Moreover, the effect of the FA/BRCA pathway in germinal cells, evidenced by infertility in patients with FA attests of chromosomal instability and cell death also occurring in the germinal compartment.

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.

Background Bone fracture fixation surgery is one of the most commonly performed surgical procedures in the orthopedic field. However, fracture healing complications occur frequently, and the choice of the most optimal surgical approach often remains challenging. In the last years, computational tools have been developed with the aim to assist preoperative planning procedures of bone fracture fixation surgery. Objectives The aims of this review are (1) to provide a comprehensive overview of the state-of-the-art in computer-assisted preoperative planning of bone fracture fixation surgery, (2) to assess the clinical feasibility of the existing virtual planning approaches, and (3) to assess their clinical efficacy in terms of clinical outcomes as compared to conventional planning methods. Methods A literature search was performed in the MEDLINE-PubMed, Ovid-EMBASE, Ovid-EMCARE, Web of Science, and Cochrane libraries to identify articles reporting on the clinical use of computer-assisted preoperative planning of bone fracture fixation. Results 79 articles were included to provide an overview of the state-of-the art in virtual planning. While patient-specific geometrical model construction, virtual bone fracture reduction, and virtual fixation planning are routinely applied in virtual planning, biomechanical analysis is rarely included in the planning framework. 21 of the included studies were used to assess the feasibility and efficacy of computer-assisted planning methods. The reported total mean planning duration ranged from 22 to 258 minutes in different studies. Computer-assisted planning resulted in reduced operation time (Standardized Mean Difference (SMD): -2.19; 95% Confidence Interval (CI): -2.87, -1.50), less blood loss (SMD: -1.99; 95% CI: -2.75, -1.24), decreased frequency of fluoroscopy (SMD: -2.18; 95% CI: -2.74, -1.61), shortened fracture healing times (SMD:-0.51; 95% CI: -0.97, -0.05) and less postoperative complications (Risk Ratio (RR): 0.64, 95% CI: 0.46, 0.90). No significant differences were found in hospitalization duration. Some studies reported improvements in reduction quality and functional outcomes but these results were not pooled for meta-analysis, since the reported outcome measures were too heterogeneous. Conclusions Current computer-assisted planning approaches are feasible to be used in clinical practice and have been shown to improve clinical outcomes. Including biomechanical analysis into the framework has the potential to further improve clinical outcome.

Patients recovering from bone disruption due to trauma or surgery need to limit movement to minimize shear force, thereby protecting callus formation and osteogenesis. Patients often use their arms to assist with functional activities, but pushing is frequently limited to <10 lb (4.5 kg). With only verbal instructions, patients’ ability to accurately limit weight-bearing (WB) force is poor. A therapeutic intervention to improve patient adherence with upper extremity (UE) WB guidelines during functional mobility using an instrumented walker could be beneficial. Therefore, the purpose of this article is to describe a feedback training protocol to improve the ability to modulate weight-bearing force in older adults and then provide an overview of the efficacy of this protocol and subsequent development of a Clinical Force Measuring Walker. An instrumented walker was used to measure UE WB during functional mobility in older healthy subjects (n = 30) before, during, and after (immediately and 2 hours) a visual and auditory concurrent feedback training session. During feedback training, force was significantly reduced with all 3 sessions as compared to baseline. When using the front wheeled walker, UE WB force during the second and third feedback training trials went down compared to the first trial. During the third feedback training trial, force was greater than the two previous trials while transferring sit-to-stand and stand-to-sit. After completion of practice with feedback, UE WB force was significantly reduced and remained so 2 hours later. These findings suggest that feedback training is effective for helping patients to modulate UE WB. Use of an instrumented walker and feedback training would be beneficial in clinical practice, especially with older patients. A more intensive feedback training with additional trials and or simultaneous visual and auditory cues during whole-practice may be needed to get UE WB below a 10 lb threshold.

Mesenchymal Stem Cells derived from bone marrow (hBM-MSCs) are utilized in tendon tissue‐engineering protocols while extra-embryonic cord-derived, including from Wharton’s Jelly (hWJ-MSC), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to hGDF-5 we supplemented each at doses of 1, 10, and 100 ng/mL and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated expression of Collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed upregulation of SCX-A (1.7-fold) at day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX (3.8-fold) and TNC (2.3-fold) after 3 days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this we explored expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines upregulating IL-1β (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold) but a greater up-regulation of IL-10 (2.5-fold). Collagen type I and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification (fibroblast-like) with a Lenght/Width ratio increase at value higher than 1, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue engineering protocols.

Background: Recently, the management of musculoskeletal disorders with the patients' own stem cells, isolated from the walls of small blood vessels, which can be found in great numbers in the adipose tissue, has received considerable attention. On the other hand, there are still misconceptions about these adipose-derived regenerative cells (ADRCs) that contain vascular-associated pluripotent stem cells (vaPS cells) in regenerative medicine. Methods: Based on our previous publications on this topic, we have developed a concept to describe the significance of the ADRCs/vaPS cells in the field of orthobiologics as briefly as possible and at the same time as precisely as possible. Results: The ADRCs/vaPS cells belong to the group of orthobiologics that are based on autologous cells. Because the latter can both stimulate a patient’s body's localized self-healing power and provide new cells that can integrate into the host tissue during the healing response when the localized self-healing power is exhausted, this group of orthobiologics appears more advantageous than cell-free orthobiologics and orthobiologics that are based on allogeneic cells. Within the group of orthobiologics that are based on autologous cells, enzymatically isolated, uncultured ADRCs/vaPS cells have several advantages over non-enzymatically isolated cells/microfragmented fat as well as over uncultured bone marrow aspirate concentrate and cultured cells (adipose-derived stem cells, bone marrow-derived mesenchymal stem cells). Conclusions: The use of ADRCs/vaPS cells can be seamlessly integrated into modern orthopedic treatment concepts, which can be understood as the optimization of a process which - albeit less efficiently - also takes place physiologically. Accordingly, this new safe and effective type of treatment is attractive in terms of holistic thinking and personalized medicine.

Gilbert Syndrome, is a benign condition characterized by persistent indirect hyperbilirubinemia due to reduced UDP-glucuronyltransferase enzyme activity. Its coexistence with other clinical disorders has important clinical and pharmacological implications. GS is known to coexist with many hemolytic conditions and may lead to diagnostic difficulty and also increased incidence of gallstones. UGT1A1 gene has been shown to be involved in the conjugation of various physiologically important endogenous and exogenous compounds, so individuals with Gilbert mutation (the variant allele UGT1A1*28) have an increased risk of toxicity of various drugs and endogenous compounds like irinotecan, steroid hormones, implicated in various human carcinoma like colorectal and breast carcinoma. Deferiprone (DFP) is an orally available chelator used in the management of iron overload in patients with Transfusion Dependent Thalassemia (TDT). In this study, fifteen out of 275 patients with TDT, had a deferiprone-induced joint deformity. Among these fifteen patients with joint deformity, eleven patients (four patients were homozygous for TA 7 repeats and seven were heterozygous for TA7 repeats) had associated gilbert mutation. Therefore, we hypothesize that patients of TDT who had underlying Gilbert mutation might have decreased enzymatic activity of UGTIA6, which metabolizes the DFP, leading to more prominent adverse effects related to DFP.

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

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.

Thyroid hormones have a catabolic effect on bone homeostasis. Hence, this study aimed to evaluate serum vitamin D, calcium, and phosphate and bone marker levels and bone mineral density (BMD) among patients with different thyroid diseases. This cross-sectional study included patients with underlying thyroid diseases (n=64, hyperthyroid; n=53 euthyroid; and n=18, hypothyroid) and healthy controls (n=64). BMD was assessed using z-score and left hip and lumbar bone density (g/cm2). Results showed that the mean serum vitamin D Levels of all groups was low (<50 nmol/L). Thyroid patients had higher serum vitamin D levels than healthy controls. All groups had normal serum calcium and phosphate levels. The bone marker levels were significantly high in the hyperthyroid group and low in the hypothyroid group. The z-score for hip and spine did not significantly differ between thyroid patients and control groups. The hip bone density was remarkably low in the hyperthyroid group. In all groups, the serum vitamin D levels were below the cutoff value. However, thyroid patients had a higher serum vitamin D level than healthy controls. The carboxy terminal collagen crosslink and procollagen type I N-terminal propeptide levels were high in hyperthyroid patients and low in hypothyroid patients. Further, hyperthyroid patients had a low hip BMD.

Achievement of solid fusion of the lumbosacral junction (L5-S1 level) is an important factor in adult spinal deformity (ASD) surgery. The purpose of this study is to explore the effectiveness and feasibility of injectable rhBMP-2 (a combination of Eschericia coli-derived rhBMP-2 and hydrogel type β-TCP carrier; NOVOSIS Inject) as a bone substitute for the fusion of lumbosacral junction. 20 patients (average age 69.1 years) diagnosed with ASD with sagittal imbalance who underwent surgical treatment including anterior lumbar interbody fusion (ALIF) in the L5-S1 level were evaluated. Injectable rhBMP-2 was applied in L5-S1 ALIF and followed-up for 1-year. Solid fusion rates and changes of clinical outcomes (Oswestry Disability Index [ODI], Visual Analog Scale [VAS] of back and leg) were measured and analyzed at 6 and 12 months after surgery. All postoperative adverse events were evaluated about the association with injectable rhBMP-2. Fusion rates were 68.4% and 100% at 6 and 12 months after surgery. Compared to baseline, ODI were improved to 45.8% and 63.7%, VAS(back) were improved to 69.2% and 72.8%, and VAS(leg) were improved to 49.2% and 64.8% at 6 and 12 months after surgery (p&lt;0.001, respectively). There were no adverse events associated with injectable rhBMP-2. Thus, injectable rhBMP-2 may be a suitable choice of a bone graft substitute when achieving solid interbody fusion in the lumbosacral junction.

Biocompatibility of ceramic materials in CaO-P2O5 system was investigated using different methods, including in vitro and in vivo tests. Ceramics based on calcium pyrophosphate Ca2P2O7 were obtained by annealing cement-salt stone from highly concentrated hardening suspensions (HCHS). Cement-salt stone was prepared using powder mixtures of calcium citrate tetrahydrate Ca3(C6H5O7)2·4H2O and monocalcium phosphate monohydrate (MCPM) Ca(H2PO4)2·H2O. These salts were mixed with each other in such a way that calcium pyrophosphate and calcium polyphosphate were present in the final ceramic product in the following weight ratios: Ca(PO3)2/Ca2P2O7 = 0/100; 5/95; 10/90 and 20/80. Distilled water was added to a homogenized powder mixtures of Ca3(C6H5O7)2·4H2O and Ca(H2PO4)2·H2O by a water/solid ratio of 0,5 by weight. The obtained suspensions were shaped using silicon molds and left to dry in air for a week. The phase composition of the obtained samples of cement-salt stone was represented by brushite CaHPO4·2H2O, monetite CaHPO4, calcium citrate tetrahydrate Ca3(C6H5O7)2·4H2O and monocalcium phosphate monohydrate Ca(H2PO4)2·H2O. According to the XRD data, the phase composition of ceramic materials after annealing in the temperature range of 800-1000 0C was mainly represented by the β-Ca2P2O7 phase. In vivo tests shown that obtained ceramic materials can be recommended for regenerative treatments for bone defects.

This study compared the Biodentine (BD) and MTA in repair of furcation perforation (FP) in a dog model in terms of inflammatory cell count and new hard tissue formation through histological and immunohistochemical evaluations. Ninety six teeth in six adult mongrel dogs were divided according to the time of repair into two groups (48 teeth/3 dogs each); immediate and delayed repair of the induced FP. Each group was divided into three subgroups (16 teeth each) according to the evaluation periods; 1, 2, and 3 months. Each subgroup was further subdivided into four subdivisions according to the material used; MTA (6 teeth), Biodentine (6 teeth), negative control (2 teeth) and positive control (2 teeth). In experimental and positive control samples, the teeth were instrumented and obturated then, a FP was performed. The perforations were sealed according to the groups and subdivisions. Histopathology and immunohistochemical analysis using Osteonectin antibodies were performed for assessment of the inflammatory cell count and new hard tissue formation. In all groups and subgroups, there were no significant differences between MTA and BD in the inflammatory cell count and new hard tissue formation (P>0.05). Biodentine can alternate the MTA as a FP repair material.

Astronauts are at risk of losing 1.0 to 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs and dietary regimens designed to preserve their musculoskeletal system. This loss is the result of microgravity-related impairment of osteocyte and osteoblast function and the consequent upregulation of osteoclast-mediated bone resorption. This review describes the ontogeny of osteoclast hematopoietic stem cells, the contributions of macrophage colony stimulating factor, activator of NFkB and the calcineurin pathways make in osteoclast differentiation, and provides details of bone formation, the osteoclast cytoskeleton, the immune regulation of osteoclasts, and osteoclast mechanotransduction on Earth, in the microgravity of space, and in conditions of simulated microgravity. The article discusses the need to better understand how osteoclasts are able to function in zero gravity and reviews current and prospective therapies that may be used to treat osteoclast-mediated bone disease.

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.

This paper presents a proof-of-concept study on the biocolonization of 3D-printed hydroxyapatite scaffolds with mesenchymal stem cells (MSCs). Three-dimensional (3D) printed biomimetic bone structure made of Calcium Deficient HydroxyApatite (CDHA) intended as future bone graft was made from newly developed composite material for FDM printing. The biopolymer polyvinyl alcohol serves in this material as a thermoplastic binder for 3D molding of the printed object with a passive function and is completely removed during sintering. The study presents the material, the process of fused deposition modeling (FDM) of CDHA scaffolds and its post-processing at three temperatures (1200, 1300, 1400 °C), as well it evaluates the cytotoxicity and biocompatibility of scaffolds with MTT and LDH release assays after 14 days. The study also includes a morphological evaluation of the cellular colonization with scanning electron microscopy (SEM) in two different filament orientations (rectilinear and gyroid). The results of the MTT assay showed that the tested material was not toxic, and cells were preserved in both orientations, with most cells present on the material fired at 1300°C. Results of the LDH release assay showed a slight increase in LDH leakage from all samples. Visual evaluation of SEM confirmed the ideal post-processing temperature of the 3D-printed FDM framework for samples fired at 1300°C and 1400°C, with a porosity of 0.3 mm between filaments. In conclusion, the presented fabrication and colonization of CDHA scaffolds have great potential to be used in the tissue engineering of bones.

Nano/micron-sized bioactive glass (BG) particles are attractive candidates for both soft and hard tissue engineering. They can chemically bond to the host tissues, enhance new tissue formation, activate cell proliferation, stimulate the genetic expression of proteins, and trigger unique an-ti-bacterial, anti-inflammatory, and anti-cancer functionalities. Recently, composites based on bi-opolymers and BG particles have been developed with various state-of-the-art techniques for tis-sue engineering. Gelatin, a semi-synthetic biopolymer, has attracted the attention of researchers because it is derived from the most abundant protein in the body, viz., collagen. It is a polymer that can be dissolved in water and processed to acquire different configurations, such as hydro-gels, fibers, films, scaffolds, etc. Searching "bioactive glass gelatin" in the tile on Scopus renders 80 highly relevant articles published in the last ~10 years, which signifies the importance of such composites. First, this review addresses the basic concepts of soft and hard tissue engineering, in-cluding the healing mechanisms and limitations ahead. Then, current knowledge on gelatin/BG composites including composition, processing and properties is summarized and discussed both for soft and hard tissue applications. This review explores physical, chemical and mechanical features and ion-release effects of such composites concerning osteogenic and angiogenic respons-es in vivo and in vitro. Additionally, recent developments of BG/gelatin composites using 3D/4D printing for tissue engineering are presented. Finally, the perspectives and current challenges in developing desirable composites for the regeneration of different tissues are outlined.

High dietary phosphate intake and poor adherence to phosphate-binding-therapy elevate the risk of hyperphosphatemia in maintenance hemodialysis (HD; MHD) patients. Therefore, chronic kidney disease-related mineral and bone disorder (CKD-MBD) indicators increase; consequently, risks of CKD-MBDs and inflammation are elevated. This double-blind, randomized control trial intervention study was designed to investigate the possibility of reducing blood CKD-MBD indicators and modulating inflammatory indicators by consuming low-phosphate (LP) meals accompanied by a minimum dose of a calcium-based phosphate binder (CaCO3). MHD patients were recruited and randomly assigned to an LP meal group (LP group) or a control group. After initial data collection, blood collection, and dietary counseling, subjects were asked to consume a washout diet for 1 week. During the washout diet period, subjects consumed their usual diet but took 1 tablet of calcium carbonate (1CaCO3) as a phosphate binder with each meal. After the washout diet period, subjects in the LP group and control group respectively consumed LP meals and regular meals twice a day for 1 week. Meat in the LP meals was boiled before the regular cooking process, but meat in control meals was not. All meals were supplied by a central kitchen so that the contents of phosphate and other nutrients could be identified. In total, 40 MHD patients completed the study program. After 1 week of the dietary intervention, the blood Ca x P product and dietary phosphate had significantly decreased in the LP group compared to the control group (p&lt;0.05). The LP group had significantly lower variations in dietary phosphate intake, blood calcium, Ca x P product, and tumor necrosis factor (TNF)-α than the control group by comparing differences between after the dietary intervention and the baseline (△after intervention - baseline, p&lt;0.05). The increase in dietary phosphate intake (△3rd - 2nd dietary phosphate intake) augmented the increase in the TNF-α level by 6.24-fold (odds ratio [95% confidence interval]: 6.24 [1.12~34.92], p&lt;0.05). These results highlighted the conclusion that LP meals accompanied by a minimum dose of CaCO3 downregulated pro-inflammation by reducing CKD-MBD indicators which was triggered by decreasing dietary phosphate intake.

Patients often need the use of their arms to assist with functional activities, but after bone disruption, pushing is frequently limited to less than 4.5 kg. No method exists to measure arm weight bearing objectively in clinical settings. This project aimed to design, construct, and test a walker for patients who need to limit arm force to prevent excessive bone stress during post-fracture (iatrogenic or traumatic) ossification. First, a qualitative study was conducted to obtain critiques of a Clinical Force Measuring (CFM) walker prototype from rehabilitation professionals. Key statements and phrases were coded that allowed “themes” to emerge from transcribed interviews, which guided device revisions. Next, a second CFM Walker prototype was designed based on the qualitative data and device criteria/constraints and finally tested. The result was fabrication of a new lightweight, streamlined, and cost-effective prototype walker with a simple visual display and auditory cue with upper limit alarms. Key features included attachments for medical equipment and thin film force-sensing resistors integrated into the walker handles that progressively activated 3 LEDs and a buzzer when arm force exceeded programmed thresholds. The innovative CFM Walker will help patients with restricted arm weight bearing, especially elderly adults, recover safer and faster in the future.

Aging, a natural process occurring in both normal and degenerative conditions, is closely associated with collagen degradation, impacting various bodily systems such as the skin. The continuous aging of the skin, influenced by both intrinsic and extrinsic factors, underscores the importance of collagen in dermatological and cosmetic contexts. Notably, collagen supplements enriched with essential amino acids like proline and glycine along with marine fish collagen have become popular for their safety and effectiveness in mitigating the aging process. To compile relevant literature on the anti-aging applications of marine collagen, a systematic search and analysis of peer-reviewed papers was conducted using reputable databases including PubMed, Cochrane Library, Web of Science, and Embase, covering publications from 1956 to 2023. From in vitro to in vivo experiments, the reviewed studies elucidate the anti-aging benefits of marine collagen, emphasizing its role in combating skin aging and promoting overall skin health. Many bioactive marine peptides exhibit diverse anti-aging properties, including free radical scavenging, apoptosis inhibition, lifespan extension in various organisms, and protective effects in aging humans. Furthermore, the peptide production of hyaluronic acid is discussed as a mechanism to fortify collagen and enhance skin moisture, contributing to the anti-aging effects of collagen supplementation. The integration of bio-tissue engineering in marine collagen applications is also explored, highlighting its proven utility in addressing skin and bone damage. Insights from this review illuminate the diverse biomedical applications of marine collagen alongside keystone molecular editing tools such as CRISPR, positioning it as a versatile resource in anti-aging interventions. However, limitations to the scope of its application exist. Thus, by delving into these nuanced considerations, this review contributes to a comprehensive understanding of the potential and challenges associated with marine collagen in the realm of anti-aging applications.

Bacterial nanocellulose (BNC) surface has a negative charge that allows the adsorption of calcium ions to initiate the nucleation of different calcium phosphate phases. The aim of this study was to investigate different methods of mineralization on three-dimensional microporous bacterial nanocellulose, to mimetize the composition, structure, and biomechanical properties of natural bone. To generate 3D microporous biomaterial, the porogen particles were incorporated during the BNC fermentation with the strain Komagataeibacter medellinensis. Calcium phosphates (CPs) were deposited on BNC scaffolds by five alternating immersing cycles with calcium and phosphate solutions. Scanning electron microscopy micrograph showed that the scaffolds have different pore sizes, between 70 and 350 µm, but the porous interconnectivity was affected by the biomineralization method and time. The crystals on the BNC surface are shown to be rod-shaped with a calcium phosphate ratio similar to that of immature bone, increasing from 1.13 to 1.6 with cycle numbers. The main mineral phases obtained by X-ray diffraction were Octacalcium Dihydrogen Hexakis (phosphate (V)) Pentahydrate (OCP). In vitro cell studies showed good cellular adhesion and higher cell viability to 95% in all the scaffolds. Osteogenic differentiation of human bone marrow mesenchymal stem cells on the scaffolds was evaluated by bone expression markers like alkaline phosphatase, osteocalcin, and osteopontin. In conclusion, it is possible to prepare 3D BNC scaffolds with controlled microporosity, which could allow osteoblast adhesion, proliferation, and differentiation.

In this work we present a versatile, rapid, and low-cost manufacturing technique to develop bioceramic scaffolds that could enhance bone tissue regeneration via microwave preparation using a commercial microwave oven. The scaffolds were prepared combining hydroxyapatite and water glass (sodium trisilicate solution), foamed by using a microwaves oven and then characterized by means of SEM-EDS, mechanical properties, infrared spectroscopy (ATR-FTIR), density and stability test in water. Furthermore, in vitro tests were performed to verify the affinity of osteoclast cells versus the so prepared scaffold. The morphology of the samples showed interconnected pores suitable for promoting tissue regeneration and vascularization while specific mechanical properties were preserved. The physicochemical characterization and the in vitro tests presented promising results for bone regenerative applications.

The type of implant at the fracture site has effects not only from biological perspective but also from mechanical perspective in fracture healing. Biodegradable implants such as magnesium (Mg) based alloys have shown faster secondary bone healing properties as compared to bioinert implants such as titanium (Ti). The general reasoning behind this is the benefit of Mg from biocompatibility perspectives. We study the effect of Ti and Mg as base materials for implants with their different mechanical properties. The focus of our work is on the displacements at the fracture site of the tibia and their influence on the stimulus for bone healing. We have found that in comparison to Ti, Mg implants have minimal stress shielding problem, only which led to better mechanical stimulus at the fracture site.

Total Hip Arthroplasty is one of the most successful surgery. However, due to the worldwide growing population life expectancy and the related incidence of age-dependent bone diseases, a growing number of cases of intra-operative fractures lead to revision surgery with high rates of morbidity and mortality. Surgeons choose the type of the implant, either cemented or cementless prosthesis, on the basis of the age, the quality of the bone and the general medical conditions of the patients. Generally, no quantitative measures are available to assess the intra-operative fracture risk. Consequently, the decision-making process is mainly based on medical operators’ expertise and qualitative information obtained by imaging. Motivated by this scenario, we here propose a mechanical-supported strategy to assist surgeons in their decisions, by giving intelligible maps of the risk fracture which take into account the interplay between actual strength distribution inside the bone tissue and its response to the forces exerted by the implant. To this end, we produce charts and patient-specific synthetic “traffic-light” indicators of fracture risk, by making use of ad hoc analytical solutions to predict the stress levels in the bone by means of CT-based mechanical and geometrical parameters of the patient. We felt that, if implemented in a friendly software or proposed as an app, the strategy could constitute a practical tool to help the medical decision-making process, in particular with respect to the choice of adopting cemented or cementless implant

Background: Implant surface topography is a key element in achieving osseointegration. Nanostructured surfaces have shown promising results in accelerating and improving bone healing around dental implants. The main objective of the present clinical and histological study is to compare, at 4 and 6 weeks, (w) bone-to-implant contact in implants having either machined surface (MAC), SLA medium roughness surface or a Nanostructured Calcium-Incorporated sur-face (XPEED®). Methods: 35 mini-implants with 3 different surface treatments (XPEED® (n=16) – SLA (n=13) – Machined (n=6), were placed in the posterior maxilla of 11 patients then, retrieved at either 4 or 6w in a randomized split-mouth study design. Results: The BIC rate measured at 4 and 6w respectively, was: 16.8 % (±5.0) and 29.0 % (±3.1) for MAC surface; 18.5 % (±2.3) and 33.7 % (±3.3) for SLA surface; 22.4 % (±1.3) and 38.6 % (±3.2) for XPEED® surface. In all types of in-vestigated surfaces, the time factor appeared to significantly increase the BIC rate (p < .05). XPEED® surface showed a significantly higher values when compared to both SLA and MAC values at 4w (p < .05). Also, at 6w, both roughened surfaces (SLA and XPEED® ) showed signifi-cantly higher values (p < .05) than turned surface (MAC). Conclusion: Nanostructured Calcium titanate coating is able to enhance bone deposition around implants at early healing stages.

Background: Painful spinal bone metastases (PSBMs) patients regularly receive palliative radiation therapy (RT) with response rates in about 2 of 3 patients. In this exploratory study, we evaluated the value of machine learning (ML) models based on radiomic, semantic and clinical features to predict complete pain response. Methods: Gross tumour volumes (GTV) and clinical target volumes (CTV) of 261 PSBMs were segmented on planning computed tomography (CT) scans. Radiomic, semantic and clinical features were collected for all patients. Random forest (RFC) and support vector machine (SVM) classifiers were compared using repeated nested cross-validation.Results: The best radiomic classifier was trained on CTV with an area under the receiver-operator curve (AUROC) of 0.62 ± 0.01 (RFC; 95% confidence interval). The semantic model achieved a comparable AUROC of 0.63 ± 0.01 (RFC), significantly below the clinical model (SVM, AUROC: 0.80 ± 0.01); and slightly lower than the spinal instability neoplastic score (SINS; LR, AUROC: 0.65 ± 0.01). A combined model did not improve performance (AUROC: 0,74 ± 0,01).Conclusions: We could demonstrate that radiomic and semantic analyses of planning CTs allowed for limited prediction of therapy response to palliative RT. ML predictions based on established clinical parameters achieved the best results.

Critical sized bone defects and articular cartilage injuries resulting from trauma, osteonecrosis or age-related degeneration are often nonhealing by the physiological repairing mechanisms, thus representing a clinic issue due to the relevant epidemiological incidence. Current treatment approaches consist of autologous or allogenic grafting, which are associated with painfulness, morbidity, risk of infections and rejection. Novel tissue-engineering approaches, aiming at the reconstruction of damaged tissues, have been proposed as alternative solutions to these conven-tional methods. These approaches are based on the combination of three fundamental compo-nents: autologous or allogenic cells, a scaffold and growth-stimulating signals, which are gener-ally referred to as the tissue engineering triad. Three-dimensional polymer networks are fre-quently used as scaffolds to allow cell proliferation and tissue regeneration. In this scenario, cryogels are giving promising results as cell scaffolds over other polymer networks, thanks to their peculiar properties. In particular, cryogels possess an interconnected porous structure and a typical sponge-like behaviour, which facilitate the cellular infiltration and ingrowth. Their properties can be appropriately adjusted to match the requirements of the specific tissue or or-gan that it is intended to regenerate. In this review it is reported the state of the art on the fabri-cation and employment of cryogels in supporting osteo or chondro-genic differentiation for the re-building of more organized tissues. Moreover, it will highlight current progress and future perspectives in the implementation of this technology in the clinical practice.

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.

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.

Using the headphone jack of a mobile phone, the proposed device connects mobile music playback through a customized red laser pointer that is cascaded to batteries and the 3.5-mm stereo plug. The red laser pointer flashes according to the frequency of the music currently playing on the mobile phone. The self-made laser pointer which wavelength is 630–650 nm and maximum output is 5 mw and it will light up when the smart phone’s music starts playing at a music frequency matching the light frequency. The frequency signal of the light received by a solar panel is converted to an electrical analog signal, and the analog current signal is amplified through the energy conversion panel and then output to the direct current motor. The motor shaft does not rotate under a small current, but rather only slightly vibrates according to the magnitude of the currents’ analog frequency. Through gripping the motor shaft with teeth, users can transmit audio to the auditory ossicles (i.e., malleus, incus, and stapes) through the dentary bones. After receiving a music signal, the auditory ossicles enable people with congenital or acquired hearing loss to access external audio.

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.

3D Printing (3DP) technology has revolutionized the field of the use of bioceramics for maxillofacial and periodontal applications, offering unprecedented control over the shape, size, and structure of bioceramic implants. In addition, bioceramics have become attractive materials for these applications due to their biocompatibility, biostability, and favorable mechanical properties. However, despite their advantages, bioceramic implants are still associated with inferior biological performance issues after implantation, such as slow osseointegration, inadequate tissue response, and increased risk of implant failure. To address these challenges, researchers have been developing strategies to improve the biological performance of 3D printed bioceramic implants. The purpose of this review is to provide an overview of 3DP techniques and strategies for bioceramic materials designed for bone regeneration. The review also addresses the use and incorporation of active biomolecules in 3D printed bioceramic constructs to stimulate bone regeneration. By controlling the surface roughness, and chemical composition of the implant, the construct can be tailored to promote osseointegration and reduce the risk of adverse tissue reactions. Additionally, growth factors, such as bone morphogenic proteins (rhBMP-2) and pharmacologic agent (dipyridamole), can be incorporated to promote the growth of new bone tissue. Incorporating porosity into bioceramic constructs can improve bone tissue formation and the overall biological response of the implant. As such, by employing surface modification, combining with other materials, and incorporation of 3DP workflow can lead to better patient healing outcomes.

Osteoconductive granulated biopolymers (OGB) are used to restore the lost volume of the jaw bone. OGB is employed as a loose fraction and exhibits physical traits common to bulk mixtures. By removing air bubbles and industrial dust from the OGB fraction through special processing, more accessible spaces are left over for the adsorption of bone growth factors. The recipient site's biological environment alters the OGB fraction's physical characteristics. This is the cause of the OGB fraction's volume changing uncontrollably during the first three weeks following surgery. Predictive indicators for describing the physical processes of osteoconduction include the compaction coefficient and adsorption capacity. Taking into account the prognostic indicators of the dynamics of changes in the physical properties of the OGB fraction in the postoperative period, 3D planning of the bioengineered structure should be done. The OGB fraction's adsorption and drainage properties are optimized by raising the purity of OGB production and preparing the biopolymer for clinical studies.

Fibrodysplasia Ossificans Progressiva (FOP) is an enigmatic, ultra-rare genetic disorder characterized by progressive heterotopic ossification, wherein soft connective tissues undergo pathological transformation into bone structures. This incapacitating process severely limits patient mobility and poses formidable challenges for therapeutic intervention. Predominantly caused by missense mutations in the ACVR1 gene, the disorder has hitherto defied comprehensive mechanistic understanding and effective treatment paradigms. This write-up offers a comprehensive overview of the contemporary understanding of FOP's complex pathobiology, underscored by advances in molecular genetics and proteomic studies. We shed light on targeted therapy, spanning genetic therapeutics, enzymatic and transcriptional modulation, stem cell therapies, and innovative immunotherapies. We also focused on the intricate complexities surrounding clinical trial design for ultra-rare disorders like FOP, addressing fundamental statistical limitations, ethical conundrums, and methodological advancements essential for the success of interventional studies. We advocate for the adoption of a multi-disciplinary approach that converges bench-to-bedside research, clinical expertise, and ethical considerations to tackle the challenges of ultra-rare diseases like FOP and comparable ultra-rare diseases. Overall, this article serves a dual role: as a definitive scientific resource for ongoing and future FOP research and as a call to action for innovative solutions to address methodological and ethical challenges that impede progress in the broader field of medical research for ultra-rare conditions.

Modern surface analysis techniques are expanding significantly possibilities in description and attribution of historical artifacts. The present study is aimed to compare analytical ability of the X-ray fluorescent analysis (XRF) typically applied for studies ceramic art items with novel surface analysis methods: time-of-flight secondary ions mass spectroscopy (SIMS) and X-ray photoelectron spectroscopy (XPS) that were applied on measurements of elemental compositions of powder raw materials for porcelain fabrication: pegmatite P-1, Vesco-prima clay, kaolin, bone earth, dolomite, and feldspar. It was shown that SIMS successfully measures light elements unnoticeable for XRF such as lithium, beryllium, boron and heavy impurities not found out by XRF such as cobalt, cerium, copper, rubidium, vanadium. XPS has found thorium in the kaolin sample that was not detected by SIMS and XRF. The paper provides also values of chemical shifts of some XPS lines observed in materials under examination. The obtained information on relations of basic and impurity elements revealed by XRF and SIMS together with XPS chemical shifts data could be used to expose contemporary falsifications of historical porcelain and to attribute porcelain items during conservation process.

The development of magnesium calcium phosphate bone cements (MCPCs) have garnered big attention. MCPCs are bioactive and biodegradable and have appropriate mechanical and antimicrobial properties for use in reconstructive surgery. In this study, the cement powders based on a (Ca + Mg)/P = 2 system doped with Zn2+ at 0.5 and 1.0 wt.% were obtained and investigated. After the mixing with a cement liquid, structural and phase composition, morphology, chemical structure, setting time, compressive strength, degradation behavior, solubility, antibacterial activities, and in vitro behaviour of the cement materials were examined. A high compressive strength of 48 ± 5 MPa (mean ± SD) was achieved for the cement made from Zn2+ 1.0-wt.%-substituted powders. The Zn2+ introduction led to antibacterial activity against Staphylococcus aureus and Escherichia coli strains, with an inhibition zone diameter up to 8 mm. Biological assays confirmed that the developed cements are cytocompatible and promising as a potential bone substitute in reconstructive surgery.

In this study, an optimized multi-material system was designed and developed to print samples in various applications, including biomedical fields (e.g., mandibular bone loss). To improve the mechanical and biological properties of scaffolds utilized for dental bone loss applications, a multi-material setup was devised, which employs digital light processing technology. This setup consists of a linear system comprising two resin vats and one ultrasonic cleaning tank, enabling the integration of diverse materials and structures to optimize the composition of the scaffold. This approach was used to print multi-material PLLA scaffolds containing 20 wt.%. HA on the interior side, and PLLA containing 1 wt.% GO on the exterior surface of the scaffold, which were evaluated mechanically and biologically after printing. The scaffold was designed using a triply periodic minimal surface (TPMS) lattice structure, which is known to possess favorable mechanical and biological properties. Various multi-material samples were successfully printed and evaluated to illustrate the multiple-material setup's potential for ensuring proper function, cleaning, and adequate interface bonding. By numerically evaluating several TMPS structures, a novel Gyroid TPMS scaffold with a nominal porosity of 50% was developed and validated experimentally. The biological properties of the scaffolds were also evaluated, including surface morphology, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay, and cell adhesion. Based on the results, multi-material components with the least contaminations with suitable mechanical and biological properties were successfully printed. By combining PLLA-HA and PLLA-GO, this innovative technique holds tremendous potential for enhancing the effectiveness of regenerative procedures in the field of dentistry.

People are increasingly encouraged to reduce animal food consumption and shift towards plant-based diets, however the implications for children’s health are unclear. In this narrative review of research in high-income settings, we summarize evidence on the increasing consump-tion of plant-based diets in children, and update an earlier systematic review regarding their associations with children’s health outcomes. The evidence indicates that vegan but not vege-tarian diets can restrict growth relative to omnivorous children, and increase the risk of being stunted and underweight although the percentage affected is relatively small. Bone mineral content is reduced in vegetarian and especially vegan children, compared to omnivores. Both vegetarian and vegan children who do not use vitamin B12 supplements manifest with B12 defi-ciency, however supplementation rectifies this problem. Both vegetarians and vegans have lower concentrations of 25 (OH)D if unsupplemented, and lower body iron stores, but usually have normal iron metabolism markers. Both groups are at risk of iodine deficiency and this might affect thyroid health. Children consuming a vegan diet have more favorable lipid profile than omniv-orous children, however the results for vegetarian diet are inconsistent and vary by outcome. Based on the same scientific evidence, national and international dietary recommendations are heterogeneous, with some countries supporting plant-based diets among infants, children and adolescents, and others discouraging them. We offer a research roadmap, highlighting what is needed to provide adequate evidence to harmonize dietary recommendations for plant-based diets in children. A number of measures should urgently be introduced at international and na-tional levels to improve the safety of their use in children.

Background: Glycogen storage diseases (GSDs), known as glycogenoses, belong to inborn metabolic defects in the glycogen metabolism pathway. Several types of GSDs are distinguished, including Ia, Ib, III, VI, and IX. GSDs manifest as excessive glycogen deposition in the liver and muscles, resulting in the dysfunction of these organs. Therefore, the treatment of choice is multitherapy that, due to dietary restrictions, may lead to nutritional deficiencies and organ complications. This study aims to assess anthropometric, body composition, skeletal status, results of selected laboratory tests, dietary, lifestyle and physical capacity analyses in patients with glycogenoses and compare the results between GSD I and GSD III-VI-IX groups. Results: The results indicate that GSD patients were overweight or obese (44% of patients had BMI +1SD or +2SD) with high percentage of fat tissue (50% of patients had above 30% of body fat) and inadequate bone mineralisation (total body less head: median z-score -0.9, L2-L4 segment: median z-score -1.65). GSD I patients had the highest risk of developing obesity (67% of them had above 30% of body fat) and osteoporosis (total body less head: median z-score -1.0, L2-L4 segment: median -1.7). Conclusions: Special attention should be paid to appropriate diet and supplementation in patients with glycogenoses.

Osteoporosis is characterized by low bone mass and structural deterioration of bone tissue with increased risk of fracture. The population that is most at risk for primary osteoporosis in-cludes post-menopausal women. Among different approaches, nutraceuticals are increasingly popular in developed countries since can contribute to bone health and can delay the onset of pathological bone loss. Our review covers three main aspects. Firstly, we discuss the current state of the two con-ditions, osteopenia, and osteoporosis. Secondly, we focus on the latest developments in natural Nutraceuticals and their effectiveness in reducing bone loss. Finally, we conduct a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis to examine the pros and cons of Nutraceuticals assumption. Nutraceuticals hold great promise, but we must address challenges such as regulatory control and experimental evidence to fully realize their potential. Other challenges include identifying the source of raw materials, ensuring the purity of the compound, avoiding contamination or the presence of other active compounds, maintaining product quality, and preventing interactions with other elements or drugs. By addressing these challenges, the scientific community can ensure more reliable indica-tions for the use of Nutraceuticals and help people lead healthier lives.

Background: The present study investigated the outcomes and possible predictive factors of autologous bone marrow cells (BMCs) therapy in patients with „no-option“ critical limb ischaemia (CLI). It was focused on exploring the clinical background and prior statin and renin-angiotensin system (RAS)-acting agent’s pharmacotherapy related to the therapeutic efficacy of BMCs treatment. Methods: In the present study, we have reviewed thirty-three patients (mean age 64.9 ± 10 years; 31 males) with advanced CLI after failed or impossible revascularisation, who were treated with 40 ml of autologous BMCs by local intramuscular application. Patients with limb salvage and wound healing (n=22) were considered responders to BMCs therapy, and patients with limb salvage and complete ischemic wound healing (n=13) were defined as super-responders. Logistic regression models were used to screen and identify the prognostic factors, and a receiver operating characteristics (ROC) curve, a linear regression and a survival curve were drawn to determine the predictive accuracy, the correlation between the candidate predictors and the risk of major amputation. Results: Based on the univariate regression analysis, baseline C-reactive protein (CRP) and transcutaneous oxygen pressure (TcPO2) values were identified as prognostic factors of the responders, while CRP value, ankle-brachial index (ABI) and bone marrow-derived mononuclear cells (BM-MNCs) concentration were identified as prognostic factors of the super-responders. An area under the ROC curve of 0.768 indicated good discrimination for CRP ˃ 8.1 mg/L before transplantation as a predictive factor for negative clinical response. Linear regression analysis revealed a significant dependence between the levels of baseline CRP and the concentration of BM-MNCs in transplanted bone marrow. Patients taking atorvastatin before BMCs treatment (n=22) had significantly improved TcPO2 and reduced pain scale after BMCs transplant, compared to the non-atorvastatin group. Statin treatment was associated with reduced risk for major amputation. However, the difference was not statistically significant. Statin use was also associated with a significantly higher concentration of BM-MNCs in the transplanted bone marrow compared to patients without statin treatment. Patients treated with RAS-acting agents (n=20) had significantly reduced pain scale after BMCs transplant, compared to the NON-RAS group. Similar results, reduced pain scale and improved TcPO2, were achieved in patients treated with atorvastatin and RAS-acting agents (n=17) before BMCs treatment. Results of the Spearman correlation showed a significant positive correlation between CLI regression, responders, and previous therapy before BMCs transplant with RAS-acting agents alone or with atorvastatin. Conclusions: CRP and TcPO2 were prognostic factors of the responders, while CRP value, ABI and BM-MNCs concentration were identified as predictive factors of the super-responders. Atorvastatin treatment was associated with a significantly increased concentration of BM-MNCs in bone marrow concentrate and higher TcPO2 and lower pain scale after BMCs treatment in CLI patients. Similarly, reduced pain scales and improved TcPO2 were achieved in patients treated with atorvastatin and RAS-acting agents before BMCs treatment. Positive correlations between responder and previous treatment before BMCs transplant with RAS-acting agents alone or atorvastatin were significant.

Medicinal plants for bone grafts are promising because they are free from infecting microorganisms and biocompatible. We report a novel study evaluating osteoregeneration of bone grafts from extracts of Alternanthera brasiliana and Fridericia platyphylla after bone injury induced by radius fracture in rats. Grafts were obtained using 2% chitosan gel and 0.5% hydroalcoholic extract. The rats were randomly divided into four experimental groups (N= 12): Negative control (NC) - Chitosan gel; Positive control (PC) - bovine mineral bone graft (Lumina Bone®, fine powder 0.5); F. platyphylla Graft (FRID) - 0.5% bone graft; A. brasiliana Graft (ABRA) - 0.5% bone graft. The animals were evaluated for three periods, 30, 60, and 90 days after fracture induction. Bone alkaline phosphatase (BSAP) and radiographic and histological evaluations were followed. After 90 days, there was an increase in BSAP for the ABRA group on the newly formed bone matrix but not for FRID, indicating the presence of active osteoblasts. Additionally, mature bone tissue and bone remodeling were observed, and a conspicuous presence of type I collagen for both FRID and ABRA. We demonstrated that FRID and ABRA grafts produced early bone neoformation. New perspectives for these species as a graft are suggested.

Thermoplastic molded regenerated silk was proposed as structural material in tissue engineering applications, mainly for application in bone. The protocol allows to obtain a compact non-porous material with a compression modulus in the order of a Giga Pascal starting from silk fibroin by compressing a silk fibroin lyophilized sponge of powder in mold at temperature higher than the glass transition temperature (Tg). The main purpose of the produced resin was the osteofixation and other structural applications in which the lack of porosity was not an issue. In this work, we introduced the use of citric acid in the thermoplastic molding protocol of SF to obtain a porosity inside the structural material. In addition to the previously developed protocols the addition of citric acid allowed us to obtain a structural material. The CA powder during the compression acted as a template for the pore formation. In addition, the CA was able to effectively crosslink the SF chain improving the mechanical strength. This effect was proved both evaluating the compression modulus and by studying the spectra obtained by Fourier infrared spectroscopy (FTIR). This protocol may be applied in the near future to the production of a structural bone scaffold.

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.

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.

Teeth include mesenchymal stem cells (MSCs), which are multipotent cells that promote tooth growth and repair. Dental tissues, specifically the dental pulp and the dental bud, constitute a relevant source of multipotent stem cells, known as dental-derived stem cells (d-DSCs): dental pulp stem cells (DPSCs) and dental bud stem cells (DBSCs). Cell treatment with bone-associated factors and stimulation with small molecule compounds are, among the available methods, the ones who show excellent advantages promoting stem cell differentiation and osteogenesis. Recently, attention has been paid to studies on natural and non-natural compounds. Many fruits, vegetables and some drugs contain molecules that can enhance MSC osteogenic differentiation and therefore bone formation. The purpose of this review is to examine research work over the past 7 years that has investigated two different types of MSCs from dental tissues that are attractive targets for bone tissue engineering: DPSCs and DBSCs. We focused on articles hypothesizing the identification and study of compounds that induce proliferation and osteogenic differentiation of the two d-DSC populations, representing an interesting issue for regenerative medicine. The reconstruction of bone defects in fact is still a challenge for personalized medicine.

Background: Despite the fact that bone reconstructive surgeries are widely practiced worldwide, the search for an ideal bone replacement matetrial is still an open issue. We aimed to provide an overview of the current status of research and developments in this field with a focus on sapphire materials; Methods: A literature search and review was conducted using the PubMed, Scopus, and Embase databases. We searched for literature using the following keywords: bone implants; biocompatible materials; bone replacement material; sapphire implants; Results: Sapphire has a unique combination of mechanical, physical and chemical characteristics thanks to wich it has an excelent biocompatability and biointegrity.Unlike other materials it is incredibly strong and has a high endurance. The successful experience of using this material in medical instrument engineering, dentistry and cardiac surgery shows its benefits; Conclusions: We consider that sapphire is a perspective material for bone replacement implants and researchers should look in this direction.

Synthetic bone made of calcium phosphate is widely used for the clinical treatment of bone defects caused by trauma and bone tumors. Although synthetic bone is easy to use, its effects are only partial depending on the size and location of the bone defect, and there are many treatment options other than the use of synthetic bone. Various biodegradable polymers that are being considered for use as scaffolds for regenerative medicine are also being considered for use as synthetic bones; however, commercial synthetic bone products with performance comparable to that of calcium phosphate bioceramics have not yet been clinically applied. This review introduces the practice of bone regeneration therapy with synthetic bone and recent research on bone regeneration therapy with biodegradable polymers.

Osteoporosis is a common problem in orthopedic medicine, and it has become an important medical issue in orthopedics as Taiwan is gradually becoming an aging society. In the diagnosis of osteoporosis, the bone mineral density (BMD) derived from dual-energy X-ray absorptiometry (DXA) is the main criterion for orthopedic diagnosis of osteoporosis, but due to the high cost of this equipment and the lower penetration rate of the equipment compared to the X-ray images, the problem of osteoporosis has not been effectively solved for many people who suffer from osteoporosis, however, at present, in clinical diagnosis, doctors are not yet able to accurately interpret X-ray images for osteoporosis manually, and must rely on the data obtained from DXA. In recent years, with the continuous development of artificial intelligence, especially in machine learning and deep learning, significant progress has been made in image recognition. Therefore, it is worthwhile to revisit whether it is possible to use a convolutional neural network model to read a hip X-ray image and then predict the patient's BMD. In this study, we proposed a hip X-ray image segmentation model and a hip X-ray image recognition classification model. First, we used the U-Net model as a framework to segment the femoral neck, greater trochanter, wards triangle, and the total hip in the hip X-ray images. We then performed image matting and data augmentation. Finally, we constructed a predictive model for osteoporosis using deep learning algorithms. In the segmentation experiments, we used intersection over union (IoU) as the evaluation metric for image segmentation, and both the U-Net and U-Net++ models achieved segmentation results greater than or equal to 0.5. In the classification experiments, using the T-score as the classification basis, the total hip using the DenseNet121 model has the highest accuracy of 74%.

In recent years, bone tissue engineering (BTE) has made significant progress in promoting the direct and functional connection between bone and graft, including osseointegration and osteoconduction, to facilitate the healing of damaged bone tissues. Herein, we introduce a new, environmentally friendly, and cost-effective method for synthesizing reduced graphene oxide (rGO) and hydroxyapatite (HAp). The method uses epigallocatechin-3-O-gallate (EGCG) as a reducing agent to synthesize rGO (E-rGO), and HAp powder is obtained from Atlantic bluefin tuna (Thunnus thynnus). The physicochemical analysis indicated that the E-rGO/HAp composites had exceptional properties for use as BTE scaffolds, as well as high purity. Moreover, we discovered that E-rGO/HAp composites facilitated not only proliferation, but also early and late osteogenic differentiation of human mesenchymal stem cells (hMSCs). Our work suggests that E-rGO/HAp composites may play a significant role in promoting the spontaneous osteogenic differentiation of hMSCs, and we envision that the E-rGO/HAp composites could serve as promising candidates for BTE scaffolds, stem cell differentiation stimulators, and implantable device components due to their biocompatible and bioactive properties. Overall, we suggest a new approach for developing cost-effective and environmentally friendly E-rGO/HAp composite materials for BTE application.

Introduction: Osteosarcomas of the jaw (OSJ) are rare tumors with a different behavior from osteosarcomas of other bones. This study aims to analyze the clinical, pathological, and therapeutic characteristics of this type of sarcoma. Methods: a retrospective observational study of cases diagnosed with OSJ registered at the “La Paz” University Hospital (Madrid). Results: Eight cases with a diagnosis of OSJ were obtained in a study period of 22 years (2000-2022). The mean age was 41 years. The distribution was 1:1 between the maxilla and mandible. Painful inflammation was the most frequent clinical manifestation. Conventional osteoblastic osteosarcoma was the most common. Survival at 5 years was 50%, while at 10 years, it decreased to 25%. Conclusions: OSJ differs from conventional osteosarcomas of long tubular bones. Surgery continues to be the mainstay of treatment; more studies are needed in which more standardized protocols can be proposed for adjuvant therapeutic management.

Single-sided deafness (SSD) refers to a condition where there is severe to profound Sensorineural hearing loss in one ear, while the other ear has normal or near-normal hearing. SSD can significantly impact an individual's ability to localize sounds, understand speech in noisy environments, and maintain spatial awareness, often resulting in a reduced quality of life and increased social isolation. In children with unilateral deafness, it can impede spoken language development and potentially impact cognitive abilities. Historically, there was a misconception that the unaffected ear could adequately support speech development in early cases and provide acceptable hearing function in adults. Consequently, SSD was frequently undertreated. However, advances in technology and a deeper understanding of the psychological and developmental impact of SSD have led to a shift in management strategies. Various treatment options are available for addressing SSD, but ongoing debate surrounds the most effective approach. These options include cochlear implants (CI), contra-lateral-routing-of-signal (CROS) devices, and bone conduction devices (BCDs). The aim of this study is to review the scientific evidence on different treatment options for SSD and compare their impact on the quality of life of individuals with this condition.

Humans are often exposed to various environmental contaminants, among which phthalates are prevalent due to their extensive use as plasticizers in various consumer goods. Di(2-ethylhexyl) phthalate (DEHP), a widely used phthalate, is recognized as an endocrine disruptor chemical (EDC). DEHP is reported to affect various organs. Few studies have addressed the effects of phthalates on bone. However, the effects of DEHP on the bone forming cells (osteoblasts) are obscure. The present study was peformed to determine the cytotoxic effects of DEHP on human osteoblasts in vitro and to delineate the mechansims. In this study, we exposed the human osteo-blastic cell line MG-63 to various concentrations of DEHP (1, 25, 50 and 100 µM) for 24, 48 and 72 h. Cell viability was assessed by MTT assay. Total RNA and protein were collected after 48 h treatment with 1 and 100 µM DEHP and determined for the mRNA and/or protein expression of alkaline phosphatase (ALP), sex steroid receptors (androgen and estrogen receptors), receptor activator of nuclear factor kappa-Β ligand (RANKL), runt-related transcription factor 2 (RUNX2) and peroxisome proliferator-activated receptor alpha (PPARα). The mRNA expression was stud-ied by real-time RT-PCR analysis and the protein expression was determined by western blot analysis. Statistical analyses were done by one-way analysis of variance (ANOVA) followed by the Students–Newman–Keuls (SNK) test. The exposure of MG-63 cells to DEHP caused a signifi-cant decrease in osteoblast viability in all the treatment groups and at all the time points stud-ied. Interestingly, DEHP exposure decreased the mRNA expression of ALP, a bone formation marker. DEHP had differential effects on estrogen receptor alpha (ERα) mRNA and protein ex-pression. However, DEHP treatment downregulated the mRNA and protein expression of ERβ, and androgen receptor (AR). Surprisingly, DEHP downregulated the RANKL mRNA expression. DEHP decreased the protein expression of RUNX2, the key transcription factor and master regu-lator of bone formation. Furthermore, DEHP increased the PPARα protein expression in the os-teoblasts. Importantly, DEHP increased the reactive oxygen species (ROS) molecules and thus oxidative stress in osteoblasts, as observed by increased hydrogen peroxide, hydroxyl radical levels and lipid peroxidation. On the other hand, it decreased the enzymatic and non-enzymatic antioxidant levels namely catalase, superoxide dismutase, glutathione peroxidase activity and reduced glutathione. Our study demonstrated that in vitro exposure to DEHP reduces the osteo-blast viability possibly through alterations in the oxidant-antioxidant system and modulation of the key genes involved in bone formation, highlighting the cytotoxic effects of DEHP on bone forming cells.

Estimating age at death is essential to establish a biological profile from human skeletal remains in both forensic and archeological settings. Imaging studies of skeletal age changes in adults have described metamorphosis of trabecular bone structure and bone loss in the proximal femur , as well as changes in morphology during different stages of life. This study aims to assess the utility of a digital representation of conventional X-ray films of the proximal femur for the estimation of age at death in a sample of 91 adult individuals (47 females and 44 males) of the Coimbra Identified Skeletal Collection. The proposed approach showed a root mean squared error (RMSE) of 17.32 years (and mean absolute error of 13.47 years) for females and an RMSE of 14.06 years (mean absolute error of 11.08 years) for males. The main advantage of this approach is the consistency in the feature detection and extraction, as X-ray images projected on the femora space will always produce the same set features to be analyzed for age estimation while more traditional methods rely heavily on operator experience which can lead to inconsistent age estimates among experts.

In recent decades, porous scaffolds for bone tissue engineering (BTE) have gained significant attention. Considerable research efforts have been dedicated to investigating the impact of scaffold pore size on a diverse array of biological processes, including cell-scaffold interactions, substance transportation, and vascularization. However, the multi-scale hierarchical porosity, a key structural characteristic of natural bone, has rarely been replicated in BTE scaffolds due to the challenges of controlling the scaffold structure across multiple length scales. With the advancement of manufacturing technology, there has been increasing research on biomimetic multi-scale hierarchical materials, which are also gaining favor in the field of BTE. Therefore, there is an urgent need to review multi-scale hierarchical porous BTE scaffolds. This paper aims to review the role and fabrication methods of multi-scale porous BTE scaffolds at different length scales, the design and manufacturing of new BTE scaffolds for bone regeneration.

nutrition, macro and micronutrients, bone health, exercise, exogenous and endogenous microRNA, epigenetics

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.

Abstract: The centrepiece of this analytical review is the metabolism of hydroxyapatite in its natural, bone, and synthetic forms, where the mitochondria-mediated mechanism may serve as the leading mechanism. The possibility that osteoblast mitochondria play an important role in the initial stages of bone mineralisation is discussed. Furthermore, the paper highlights the key role of mitochondria in the metabolism of synthetic hydroxyapatite.Differences between the results of in vivo and in vitro studies using synthetic hydroxyapatite of different morphologies are also detailed. It is noted that long-term infiltration with immune cells and in vivo studies are necessary to adequately evaluate hydroxyapatite as a bone-plastic material.Particular attention is given to the interaction of hydroxyapatite with immune cells and its ability to affect the ribosomes and mitochondria of cells. Due to its mechanical properties, scalability and potential use for the treatment of extensive bone defects of tumor origin, hydroxyapatite is a promising material.This study also highlights the importance of further development of in vitro research methods in the context of their biomimeticity. Overall, this work offers a theoretical direction for future studies of hydroxyapatite as a bone grafting material and emphasises the value of in vivo studies.

(1) Background : Low dietary intake of calcium, vitamin D, vitamin C and magnesium has been associated with increased risk of osteoposrosis. The purpose was to evaluate changes in biomarkers of bone metabolism, and cardiometabolic health in postmenopausal women, with high risk of osteoporosis, followed by a nutritional intervention program. (2) Method: It was a prospective randomized controlled trial. A sample of 115 apparently healthy postmenopausal women(45 -75 years of age) randomized into four groups: (I) nutritional intervention group(n=40) received daily 1000mg vitamin C, 500mg vitamin D3, 500mg calcium(Ca) and 300mg magnesium (Mg); (II) control group(n=42) received daily 500mg vitamin D3, 500mg Ca and 300mg Mg; (III) nutritional intervention group (n=18) received daily 150mg bisphosphonates, 500mg vitamin D3, 500mg Ca and 300mg Mg; and (IV) nutritional intervention group (n=15) received daily about 364 mg polyphenols via an innovative functional food (50g olive paste enriched with mountain tea extract) along with 500mg vitamin D3, 500mg Ca and 300mg Mg. Groups I -III received supplementation for a year whereas group IV for 5 months. Changes in calciregulatory hormone parathormone (PTH) were evaluated at the beginning of the study as well as at 5 and 12 months intervals. Blood levels of vitamin D, vitamin C, Ca, Mg and the lipid profile were assessed at the beginning and at the end of the study. Anthropometric indices (weight, body fat(Kg), Body Mass Index(BMI) and bone mineral density(BMD) were evaluated at the beginning and at the end of the study. Statistical analysis was performed with IBM-SPSS Statistics-21. The level of statistical significance was set at p<0.05. (3) Results: 25(OH)D3 levels were improved, in groups II, III and IV (+3,71% and +1.45% and +5.62% respectively). PTH levels were increased at the end of the intervention period, for groups I and IV. Significant positive changes recorded, in total BMD, in all four study groups. Significant beneficial changes for total cholesterol was observed in group IV (-2.07%, P<0.05) and positive changes in group I for HDL biomarker (+61.62%, P<0.05) (4) Conclusions:. Additional larger-scale clinical trials and intervention studies are considered essential, in order to fully investigate and elucidate associations between dietary components and biochemical indices of bone metabolism.

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.

The purpose of this study was to clarify the attachment types of the tibialis anterior tendon (TAT) in Japanese fixed cadavers and to determine the attachment site area in three dimensions. We examined 100 feet from 50 Japanese cadavers. The TAT was classified according to differences in the number of fiber bundles as: Type I, with one fiber bundle; Type II, with two fiber bundles; and Type III, with three fiber bundles. The attachment site area of the TAT was measured using a three-dimensional scanner. Cases were Type II in 95% and Type III in 5%, with no cases of Type I identified. In Type II, mean attachment site areas were 85.2 ± 18.2 mm2 for the medial cuneiform bone (MCB) and 72.4 ± 19.0 mm2 for the first metatarsal bone (1MB), showing a significantly larger area for MCB than for 1MB. These findings suggest the possibility of ethnic differences in TAT attachment types and suggest that TAT attachments in Japanese individuals are highly likely to be Type II, with rare cases of Type III. Accurate measurement of attachment site areas is possible with appropriate three-dimensional measurements.

Rosavin, a phenylpropanoid in Rhodiola rosea's rhizome, an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular metabolism in health and many diseases, particularly influencing bone tissue metabolism. In vitro, rosavin inhibits osteoclastogenesis, disrupts F-actin rings formation, and lowers osteoclastogenesis-related gene expression (cathepsin K, CTR, TRAF6, TRAP, MMP-9). It also impedes NFATc1, c-Fos, NF-κB, and MAPK signaling pathways, and blocks phosphorylation processes crucial for bone resorption. Moreover, rosavin promotes osteogenesis, osteoblast differentiation and increases Runx2 and OCN expression. In vivo studies show its effectiveness in enhancing BMD in PMOP mice, re-straining osteoclast maturation, and increasing active osteoblast percentage in bone tissue. It modulates mRNA expressions (increasing EEF2 and decreasing HDAC1, thereby activating os-teoprotective epigenetic mechanisms) and alters various serum markers, including decrease of CTX-1, TRAcp5b, RANKL, M-CSF, TRAP, and increase of ALP and OCN. Additionally, when combined with zinc and probiotics, it reduces pro-osteoporotic MMP-3, IL-6, TNF-α, and en-hances anti-osteoporotic IL-10 and TIMP3 expressions. This paper aims to systematically review rosavin's impact on bone tissue metabolism, exploring its potential in osteoporosis prevention and treatment, and suggesting future research directions.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder but kidneys are not the only organs involved in this systemic disorder. Individuals with the condition may display additional manifestations beyond the renal system, involving liver, pancreas and brain in the con-text of cystic manifestations, while vascular system, gastrointestinal tract, bones, and cardiac valves in the context of non-cystic manifestations. Despite kidney involvement remain the main feature of the disease, thanks to new generation therapies, early diagnosis and better management of kidney related problems, a new wave of complications must be faced from clinicians who treated polycystic patients. Involvement of the liver represents the most prevalent extrarenal manifestation and grows importance in symptom burden and quality of life. Vascular abnormalities are a key factor for patients’ life expectancy and there’s still de-bate whether to screen or not to screen all patients. Arterial hypertension is often the earliest onset among polycystic patients leading to frequent cardiovascular complications. Although cardiac valvular abnormali-ties is a frequent complication, it rarely leads to relevant problems in the clinical history of polycystic pa-tients. One of the new relevant aspects concern bone disorders, that can exert a considerable influence on the clinical course of these patients. This review aims to provide the “state of art” among extrarenal mani-festation of ADPKD.

Segmental bone defects caused by trauma, infection, tumor resection or osteoporotic fractures present significant surgical treatment challenges. Host bone autograft is considered the gold standard to restore function but comes with the cost of harvest site comorbidity. Allograft bone is a secondary option but has its own limitations in incorporation with host bone as well as cost. Therefore, developing new bone tissue engineering strategies to treat bone defects is critically needed. In the past three decades, the use of stem cells delivered with different scaffolds or growth factors for bone tissue engineering has made tremendous progress. Many varieties of stem cells have been isolated from different tissues for use in bone tissue engineering. This review summarizes the progress in using different postnatal stem cells including bone marrow mesenchymal stem cells, muscle-derived stem cells, adipose-derived stem cells, dental pulp stem cells/periodontal ligament stem cells, periosteum stem cells, umbilical cord-derived stem cells, peripheral blood stem cells and urine-derived stem cells for bone tissue engineering and repair. This review also summarizes the progress using exosomes or extracellular vesicles delivered with various scaffolds for bone repair. The advantages and disadvantages of each type of stem cell are also discussed and explained in detail. It is hopeful in the future that these preclinical results will translate into new therapies for bone defect repair.

Background: In regenerative dentistry the graft material influences the success. It should act as an osteoconductive scaffold, providing a mineral substrate during resorption and inducing the activity of osteoinductive cells capable of producing new bone, platelet growth factors, and cell differentiation factors inducing the differentiation of undifferentiated mesenchymal cells into. Given that dentin shares many biochemical characteristics with bone tissue, it has recently attracted considerable interest as a biomaterial for bone repair. The aim of this study is to compare two grinder types in order to determine the optimal method for producing dentinal particles using a mechanical grinder. Materials and methods: A sample of 40 natural human teeth without restorations, prostheses or root canal treatments was used and divided into two groups subjected to two different grinder speeds (high-speed and low-speed). The high-speed showed a greater dispersion (53.5+-9.89% of the tooth) due to the pulverisation (highly thin granules) of part of the tooth. The low-speed grinder does not pulverize the dentin and the percentage of tooth loss is 9.16+/-2.34%. Conclusion: The low-speed gringer allows to save a major part of the tooth and to have a maximum quantity of graft material but requires more time. Further studies must be promoted to optimise the grinding procedures.

When bone substitutes materials are used, the increased risk of infection due to the none-autogenic graft is often discussed. The treatment of large bone defects in geriatric patients, often with osteoporotic bone, often presents major challenges to surgery. Bone substitutes materials are available indefinitely without the risk of additional surgery in each patient. Can bone substitutes materials be used without hesitation in the geriatric patient?Eighty-three patients suffered traumatic fractures of the distal radius, proximal humerus, and proximal tibia. The defect zones were filled with bone substitute material based on nanocrystalline hydroxyapatite (NHA) or calcium phosphate (CP). For comparison, a reference group without the void filling with a bone graft substitute (void defects, ED) was studied. All patients over the age of 64 years were retrospectively evaluated for complications and radiological outcomes. Results: 106 patients sustained traumatic fractures of the distal radius (68.9%), proximal humerus (5.7%), and proximal tibia (22.6%). No differences in infections were found when comparing the groups (p=1.0). retrospectively evaluated. The KEM group had a nonsignificantly lower rate of pseudarthrosis (p=0.09). A relative risk (RR) reduction of complications of 32.64% was observed when bone grafting material was used. The NNT for the prevention of complications was 5.99. When bone healing was assessed by radiological images, some follow-up studies showed significant differences in fracture bridging (p<0.001).Conclusions: In contrast to previous studies, bone substitutes materials can support the healing process in geriatric patients without relevant disadvantages. With an NNT of 6 regarding complications, many patients could benefit from bone graft augmentation. No increased infection rate was observed.

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.

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.

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

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.

Consumption of prunes has been shown to slow bone loss after menopause in American women but there is no data on its effects in Asian women. 135 postmenopausal Korean women with osteopenia were randomized to 100g/day of prunes or no prunes with 600U vitamin D and 800mg of calcium for 12 months. Bone density was measured at baseline and 12 months in the lumbar spine, both hips and the L forearm. Serum levels of CTX and P1NP and vitamin D calcium and phosphate were measured at baseline, 6 and 12 months. PTH was measured at baseline if vitamin D was low Four women dropped out of each group over the 12 months. There was no difference between groups in blood measures or bone density in any region over the 12 month trial., In conclusion 100g/day of prunes has no effect in Korean woman on bone density or bone markers.

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.

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.

This review provides a comprehensive overview of two major advancements in hearing loss treatment: the middle ear implant (MEI) and bone conduction implants (BCIs). MEI, surgically inserted in the middle ear, directly stimulate the ossicles, and are primarily employed to treat sensorineural, conductive, or mixed hearing losses. BCIs work via bone conduction, bypassing the outer and middle ear to deliver sound vibrations to the inner ear, beneficial especially for conductive or mixed hearing losses and single-sided deafness. The decision to opt for these devices is a multifaceted process, considering audiological criteria, surgical feasibility, and patient expectations. The review also details the portfolio of available devices, their functioning, and audiological usage indications. While both MEI and BCIs prove beneficial for patients, the review emphasizes the need for careful preoperative planning and counselling, considering factors such as potential complications, surgical challenges, and patient suitability. Overall, the two types of implants, despite their individual complexities, provide an effective alternative to traditional hearing aids, offering a path to improved sound clarity and quality for patients with various types of hearing loss.

Laser patterning of implant materials for bone tissue engineering purposes has shown to be a promising technique to control cell properties such as adhesion or differentiation, resulting in an enhanced osteointegration. However, the perspective of patterning the bone tissue side interface to generate microstructure effects has never been investigated. In the present study, three different laser-generated patterns were machined on the bone surface with the aim to identify the best surface morphology compatible with osteogenic-related cells recolonization. The laser patterned bone tissue was characterized by electron scanning microscopy and confocal microscopy in order to obtain a comprehensive picture of the bone surface morphology. Cortical bone patterning impact upon cell compatibility and cytoskeleton rearrangement to the patterned surfaces was performed with Stromal Cells from Apical Papilla (SCAPs). Results indicated that laser machining had no detrimental effect upon consecutively seeded cells metabolism. Orientation assays revealed that surface patterning characterized by larger hatch distances was correlated with a higher cell cytoskeletal conformation to the laser-machined patterns. For the first time, to our knowledge, bone is considered and assessed here as a potentially engineered-improvable biological interface. Further studies shall focus on in vivo implications of this direct patterning.

Oral bone defects occur as a result of trauma, cancer, infections, periodontal diseases, and caries. Autogenic and allogenic grafts are the gold standard used to treat and regenerate damaged or defective bone segments. However, these materials do not possess the antimicrobial properties necessary to inhibit the invasion of the numerous deleterious pathogens present in the oral microbiota. In the present study poly(ε-caprolactone) (PCL), nano-hydroxyapatite (nHAp), and a commercial extract of Humulus lupulus L. (hops) were electrospun into polymeric matrices to assess their po-tential for drug delivery and bone regeneration. The fabricated matrices were analyzed by scanning electron microscopy (SEM), tensile analysis, thermogravimetric analysis (TGA), FT-IR assay, and in vitro hydrolytic degradation. The antimi-crobial properties were evaluated against the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. The cytocompatibility was proved by the MTT assay. SEM analysis proved the nanostructured matrices have suitable fiber size. The present research provides new information about the interaction of natural compounds with ceramic and polymeric biomaterials. The hop extract and other natural or synthetic medicinal agents can be effectively loaded into PCL fibers and has the potential to be used in biomedical applications.

The phytonutraceutical Ormona® is a product composed of: purified oil of Bixa orellana Linné; dry extract of Myrciaria dubia McVaugh; dry extract of Trifolium pratense L. and dry extract of Euterpe oleracea Mart. obtained using Evolve® technology. This study evaluated the effects of Ormona® on Wistar rats affected by ovariectomy-induced osteoporosis. Pre-treatment was conducted for 15 days before surgery and continued for a further 45 days after the surgical procedure. The experimental design consisted of 5 groups (n=5): OVW: treated with distilled water (1 mL/ kg, p.o); ADS: alendronate sodium (4 mg/ kg p.o); EST: conjugated estrogen (2 ug/ kg, p.o); ORM: Ormona® (20 mg/kg, p.o); ORM + EST: Ormona® (20 mg/kg + conjugated estrogen 2 ug/ kg, p.o. Biochemical and hormonal parameters, along with bone histopathology and trabecular and femoral diaphysis size, were evaluated through Scanning Electron Microscopy (SEM) and bone calcium quantification by atomic absorption spectrophotometry. The results show that ovariectomy caused bone alterations such as loss of femoral microarchitecture, decreased bone homeostasis parameters, and changes in the lipid profile. Estrogen supplementation reduced parameters such as cholesterol, LDL, and Ca2+ concentration. However, Ormona® showed higher serum estradiol levels (p&lt; 0.01), effects on the lipid profile, including parameters that estrogen replacement and alendronate sodium did not affect, with an increase in HDL, and positive modulation of bone metabolism, increasing osteocytes and the presence of osteoblasts. Ormona®, therefore, produced better results than the groups treated with estrogen and alendronate sodium.

Mild impacts to the head, particularly when repetitive in nature, are increasingly recognized to have a range of significant negative implications for brain health. Much of the ongoing research in the field is focused on the neurological consequences of these injuries, and the relationship between head impacts and long-term neurodegenerative conditions such as chronic traumatic encephalopathy and Alzheimer’s disease. However, our understanding of the complex relationship between applied mechanical force at impact, brain pathophysiology, and neurological function, remains incomplete. Past research has shown that mild head impacts, even below the threshold that results in cranial fracture, induce changes in cranial bone structure and morphology. These structural and physiological changes likely have implications for the transmission of mechanical force into the underlying brain parenchyma. Here, we review this evidence in the context of the current understanding of bone mechanosensitivity and the consequences of traumatic brain injuries or concussions. We postulate that heterogeneity of the calvarium including differing bone thickness due to prior impacts, age, or individual variability, may be a modulator of outcomes following subsequent head impacts. We advocate for greater consideration of cranial responses to head injury in both experimental and computer modeling of impact biomechanics, and raise the hypothesis that calvarial bone thickness represents a novel biomarker of brain injury vulnerability after head trauma.

It is known that complexes based on natural polysaccharides are able to eliminate bone defects. Prolonged hyperglycemia means low bone regeneration and a chronic inflammatory response. The purpose of the study was to increase the efficiency of early bone formation in a cavity of critical size in diabetes mellitus in the experiment. The polyelectrolyte complex contains high molecular ascorbate of chitosan, chondroitin sulfate, sodium hyaluronate, heparin, adgelon serum growth factor, sodium alginate and amorphous nanohydroxyapatite (CH-SA-HA). Studies were conducted on 5 groups of white female Wistar rats: group 1 - regeneration of a bone defect in healthy animals under a blood clot; group 2 - regeneration of a bone defect under a blood clot in animals with diabetes mellitus; group 3 - bone regeneration in animals with diabetes mellitus after filling the bone cavity with a collagen sponge; group 4 - filling of a bone defect with a CH-SA-HA construct in healthy animals; Group 5 - filling of a bone defect CH-SA-HA in animals with diabetes mellitus. Implantation of the CH-SA-HA construct into bone cavities in type I diabetic rats can accelerate the rate of bone tissue repair. The inclusion of modifying polysaccharides and apatite agents in the construction may be a prospect for further improvement of the properties of implants.

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.

Pericytes, as perivascular cells, are present in all vascularized organs and tissues, and they actively interact with endothelial cells in capillaries and microvessels. Their involvement includes functions like blood pressure regulation, tissue regeneration, and scarring. Studies have confirmed that pericytes play a crucial role in bone tissue regeneration through direct osteodifferentiation processes, paracrine actions, and vascularization. Recent pre-clinical and clinical experiments have shown that combining perivascular cells with osteogenic factors and tissue-engineered scaffolds can be therapeutically effective in restoring bone defects. This approach holds promise for addressing bone-related medical conditions. In this review, we have emphasized the characteristics of pericytes and their involvement in angiogenesis and osteogenesis. Furthermore, we have explored recent advancements in the use of pericytes in preclinical and clinical investigations, indicating their potential as a therapeutic resource in clinical applications.

The purpose of this study was to explore and develop high-resolution infrared thermal (HRIT) imaging for screening toddler’s fracture. A Toddler’s fracture is a common tibial fracture of children younger than 6 years old. Initial x-ray radiographs may not show the fracture and another x-ray during a follow-on visit is usually required. The study included 39 participants admitted to an emergency department with a suspected toddler’s fracture. X-ray confirmed 8 cases with a toddler’s fracture (20.5%). Infrared images of participants were recorded on their index visit, focusing on region-of-interests on the injured and the contralateral (uninjured) legs. The uninjured leg acted as a thermal reference. Nine statistical measures were extracted from the images: maximum, mini-mum, mean, standard deviation, median, mode, interquartile range, skewness, and kurtosis. Wilcoxon rank sum test indicated that maximum, mean, standard deviation, median, and inter quartile range temperature measures were significantly different (p<0.05) when comparing fractured and non-fractured legs. Principal component analysis of these measures highlighted distinct separation of toddler’s fracture and non-fracture cases. Similarly, plots of the statistical measures further confirmed clustering of toddler’s fracture cases. The study demonstrated that HRIT imaging can be a valuable tool for screening for toddler’s fracture.

Vitamin D deficiency and insufficiency are highly prevalent in CKD affecting over 80% of hemodialysis (HD) patients and require therapeutic intervention. Nephrological societies suggest the administration of cholecalciferol according to the guidelines for the general population. The aim of the observational study was to evaluate the efficacy and safety of the therapy with a high dose of cholecalciferol in HD patients with 25(OH)D deficiency and insufficiency to reach the target serum 25(OH)D level &gt; 30 ng/mL. 22 patients (16 M), with an average age of 72.5 ± 13.03 years and 25(OH)D concentration of 13.05 (9.00–17.90) ng/mL were administered cholecalciferol at a therapeutic dose of 70,000 IU/week (20,000 IU + 20,000 IU + 30,000 IU, immediately after each dialysis session). All patients achieved the target value &gt;30 ng/mL, with a mean time of 2.86 ± 1.87 weeks. In the first week, the target level of 25(OH)D (100%) was reached by 2 patients (9.09%), in the second week – by 15 patients (68.18%), in the fourth week – by 18 patients (81.18%) and in the ninth week by all 22 patients (100%). A significant increase in 1,25(OH)2D levels was observed during the study, however, only 2 patients (9.09%) achieved a concentration of 1,25(OH)2D above 25 ng/mL – the lower limit of the reference range. The intact PTH concentrations remained unchanged during the observation period. No episodes of hypercalcemia, and one new episode of hyperphosphatemia were observed. In conclusion, our study showed that the administration of a high therapeutic dose of cholecalciferol allowed for a quick, effective, and safe leveling of 25(OH)D concentration in HD patients.

Pain in osteoarthritis (OA) results from erosion of joint cartilage, resulting in bone contacting bone without an intervening cushion. The periosteum, including its nociceptive innervation, ends at the border of the cartilage meaning that there is no extrinsic neuronal pathway between the opposing denuded bone surfaces to carry a bone-on-bone pain signal to the brain. The pain signaling pathway must therefore originate in nociceptive sensory endings within the subchondral bone itself. Selective ablation of this intrinsic nerve pathway, using any of a variety of approaches, is expected to permanently eliminate OA pain.

Articular cartilage healing and repair is one of the biggest clinical challenges in trauma and orthopaedic medicine, leading to high economic loss due to athletic impairment in sport horses. Multipotent Mesenchymal stem/stromal cells are part of novel therapeutic arsenal aimed at tissue regeneration and restoring organ function. These cells release biomolecules and factors in the culture media, producing the so called conditioned medium, which have a pro-regenerative effect through paracrine mechanisms. Considering this, a therapeutic product combining equine synovial membrane derived Mesenchymal stem/stromal cells and equine umbilical cord stroma-derived Mesenchymal stem/stromal cells conditioned medium was employed. In this work the treatment of two articular defects, in the first phalanx and third metacarpus of the left front limb of a five-year-old horse, is described. Following surgical debridement of the lesions, the treatment comprised two intra-articular administrations of the above-mentioned therapeutic combination, 15 days apart. This was followed by a thorough rehabilitation program. A second-round treatment was performed 6 months later. Diagnostic imaging demonstrated significant improvement of the articular defects. The clinical outcome allowed a full return to the athletic performance demonstrating the safety and potential advantages of this approach when compared with other therapeutic options.

Introduction: Silver nanoparticles have been extensively investigated in dental and orthopedic materials. However, the impregnation of bone graft with silver nanoparticles has been poorly investigated. Objectives: The aim of this study was to evaluate the in vitro antibiofilm activity of a bovine bone impregnated with silver nanoparticles. Methods: Bone scaffolds from cancellous bovine femur were used for the tests and impregnated with silver nanoparticles (50nm) by physical adsorption. Silver nitrate minimal inhibitory and bactericidal concentration were performed Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Enterococcus faecalis, Acinetobacter baumannii, and Escherichia coli. Disc diffusion tests for silver nanoparticles susceptibility and quantification of biofilm production on plate and bone with sessile cell count were also performed. Results: All pathogens were susceptible to silver with low minimal inhibitory concentration (0.25 – 4 mg/L). The scaffold impregnated with silver nanoparticles presented a significant reduction in the biofilm cells for all microorganisms with a reduction of more than 3 logs in colony forming units count. Conclusion: Bone scaffolds impregnated with silver nanoparticles can significantly reduce biofilm, and it can be a strategical material to be used as an implant for different approaches.

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.

Despite improved knowledge regarding diagnosis and treatment of osteomyelitis of the jaw (OMJ), it remains a clinical challenge for oral and maxillofacial surgeons. This study aimed to identify risk factors associated with severe forms of OMJ, i.e. related to the occurrence of major complications or the refractory course of the disease. A retrospective study was performed based on the medical records of all patients diagnosed with OMJ from the past 20 years. Collected data included demographic information, medical and dental history, clinical, radiological, and bacterial findings as well as treatment modalities. The main outcome variables were the onset of major complications and treatment results. Fifty-four patients were included. Our results showed that alcohol and smoking habits, as well as malnutrition, were significantly associated with the occurrence of major complications. We also established that dental implant–induced OMJ should be considered as an aggressive subtype of OMJ. Finally, clinical bone exposure was significantly associated with unfavorable outcomes, whereas dental causes or radiological evidence of periosteal reaction were predictive of successful outcomes. Identifying such factors could be useful in preventing serious complication and informing patients about the refractory course of the disease based on the presence of these factors.

Background: TP53 alterations have a significant prognostic effect in myeloid neoplasms. Our objective was to investigate the TP53 gene mutation status, p53 protein expression, and their re-lationship in dysplasia-related myeloid neoplasms with varying levels of myeloblast counts. Methods: 76 bone marrow biopsy samples with different blast counts were analyzed. Total and strong (3+) p53 expression was determined. Dual immunohistochemical staining was performed to determine the cell population associated with p53 expression. NGS analysis was performed using the Accel-Amplicon Comprehensive TP53 panel. Results: Both p53 expression and TP53 VAF showed a significant correlation with the myeloblast ratio (p<0.0001), however, p53 expres-sion was present in other cell lineages as well. The VAF value exhibited a significant correlation with p53 expression. A high specificity (0.9800) was observed for TP53 mutation using the ≥10% strong (3+) p53 cut-off value, although the sensitivity (0.4231) was low. Conclusion: Strong (3+) p53 expression using a ≥10% cut-off value accurately predicts TP53 mutation but doesn't reveal the allelic state. The p53 expression is significantly influenced by myeloblast count, and histo-logical interpretation should consider the presence of intermixed non-neoplastic marrow cells with varying physiological p53 expression.

Background: Diabetes mellitus (DM) and osteoporosis are two of the most widespread metabolic disease in the world. The aim of this study is to investigate the prevalence of DM among patients affected by osteoporosis and fragility fractures, and to search differences in clinical features. Methods: 713 patients belonging to CTO Bone Unit because of osteoporosis and fragility fractures were divided into two groups, according to the diagnosis of DM. The clinical and bone characteristics of patients were compared. Results: Prevalence of DM was 10.8%. When compared to patients without DM, the median age at the time of first fracture was similar (72 years ± 14 IQR vs 71 years ± 12 IQR); prevalence of combination of vertebral and hip fractures was higher (p=0.039), as well as prevalence of males, although not significantly (p=0.051). Bone mineral density (BMD) at all sites was higher in DM group; Trabecular Bone Score (TBS), instead, was significantly lower (p&lt;0.001). Conclusions: Patients with fragility fractures and DM more frequently show combination of major fractures with higher BMD levels. In these patients, TBS could be a better indicator of bone health than BMD and therefore should be used as a diagnostic tool in clinical practice.

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.

Abstract. Graphene family (GF)-Calcium phosphate (CaP) composites, holds great potential as components of bone regeneration materials. GF nanomaterials can be modified physically as well as chemically, which are to be biomimetic, mechanically to be hard due to their capability to support exceptional mechanical, thermal and electronic properties. These biocompatible GF composites coated on the calcium phosphate can enhance and tolerate stem cell growth and differentiation, proliferation into various lineages or interact with bioorganisms. The development in CF-CaP materials and their physicochemical/biointeractions and strategies towards osteoblasts is a great concern to promote faster healing and reconstructions of large bone imperfections or defects. In this review, we explain the influence of the CF-CaP and summarize recent developments on designing CF-CaP architectures as multifunctional bone regeneration platforms. We have also explored the typical biological applications concerning these CF-CaP based bioactive nanocomposites. Furthermore, the future viewpoints and evolving challenges will also be emphasized. Due to the shortage of full-length reviews in this emerging research field, this review would be caught great attention and encourage various new chances across a wider range of disciplines.

Parathyroid-hormone-related protein (PTHrP) is encoded by PTHLH gene which, by alternative promoter usage and splicing mechanisms, can give rise to at least three isoforms of 139, 141 and 173 amino acids with distinct C-terminals. PTHrP is subjected to different post-translational processing that generates smaller bioactive forms, comprising amino terminus, midregion (containing a nuclear/nucleolar targeting signal) and carboxy terminus peptides. Both the full-length protein and the discrete peptides are key controllers of viability, proliferation, differentiation and apoptosis in diverse normal and pathological biological systems via the reprogramming of gene expression and remodulation of PKA or PKC-mediated signalization mechanisms. The aim of this review is to pick up selected studies on PTHrP-associated signatures as revealed by molecular profiling assays, focusing on the available data about exemplary differentiating, differentiated or non-tumoral cell and tissue models. In particular, the data presented relate to adipose, bone, dental, cartilaginous and skin tissues, and also intestinal, renal, hepatic, pulmonary and pancreatic epithelia, with a focus on hepatic fibrosis-, pancreatitis- and diabetes-related changes as diseased states. Whether reported, the biochemical and/or physiological aspects associated with the specific molecular modulation of gene expression and signal transduction pathways in the target model systems under examination will be also briefly commented.

This review summarises the complex relationship between medications used to treat type 2 diabetes, and bone health. T2DM patients face an increased fracture risk despite higher bone mineral density, thus we analysed the impact of key drug classes, including Metformin, Sulphonylureas, SGLT-2 inhibitors, DPP-4 inhibitors, GLP-1 agonists, and Thiazolidinediones. Metformin, despite promising preclinical results, lacks a clear consensus on its role in reducing fracture risk. Sulphonylureas present conflicting data, with potential neutral effects on bone. SGLT-2 inhibitors seem to have a transient impact on serum calcium and phosphorus, but evidence on their fracture association is inconclusive. DPP-4 inhibitors emerge as promising contributors to bone health, as well as GLP-1 agonists exhibit positive effects on bone metabolism, reducing fracture risk. Thiazolidinediones, however, demonstrate adverse impacts on bone, inducing loss through mesenchymal stem cell effects. Insulin presents a complex relationship with bone health. While it has an anabolic effect on bone mineral density, its role in fracture risk remains inconsistent. In conclusion, a comprehensive understanding of diabetes medications' impact on bone health is crucial. Further research is needed to formulate clear guidelines for managing bone health in diabetic patients, considering individual profiles, glycemic control and potential medication-related effects on bone.

Background and Objectives: The healing of bone defects is a serious challenge worldwide. One branch of dentistry deals with bone defects. capsaicin has anti-inflammatory, anti-oxidative and cholesterol-reducing effects. The aim of this study is to evaluate the effects of systemic capsaicin administered at different doses on bone healing. Materials and Methods: A total of 32 male wistar rats was used, their weight varying between 250 and 300 g. The rats were randomly divided into four groups of eight rats each. The analyses served to evaluate the effect on healing of different doses of capsaicin and grafts. A significant increase was observed in the number of osteoblasts in the capsaicin-applied groups compared to the control group. Conclusions: As a result of the analyses, positive effects on bone healing were observed when capsaicin 0.25 mg/kg and 0.50 mg/kg was administered intraperitoneally. However, more studies are needed for more accurate information.

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.

Keywords: artificial bone; conical implants; cylindrical implants; dental implants; implant stability quotient; insertion torque; polyurethane; post-extraction sites; removal torque.

Tissue bioengineering has been assuming a pivotal role in implementing alternatives to conven-tional ossicular middle ear replacement prostheses to overcome extrusion while preserving acoustic properties. This in vitro study aims to explore for the first time in current literature the feasibility of a biohybrid middle ear prosthesis composed of titanium surrounded by bone ex-tracellular matrix as bio-coating. We have hereby studied the adhesion and proliferation of human adipose-derived mesenchymal stem cells (hASC) on titanium scaffolds in vitro. Moreover, we identified the osteogenic differentiation of hASC using immunofluorescence assay to analyze osteoblasts gene expression profile (Alp, Runx2, Col1a1, Osx, and Bglap) and we accounted the presence of collagen as a marker of hASC ability to secrete extracellular matrix. We utilized scanning electron microscopy to evaluate the presence of extracellular matrix on the scaffolds. Our preliminary data demonstrated the titanium ability to support human adipose-derived mesenchymal stem cell colonization, proliferation, and osteoblastic differentiation, to obtain a biohybrid device. Our experience seems encouraging, we advocate further in vivo research to corroborate our results towards bone transplantation.