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.

Implants are used to replace damaged biological structures in human body. Although stain-less-steel (SS) is a well-known implant material, corrosion of SS implants led to the release toxic metallic ions which produce harmful effects in human body. To prevent material degradation and its harmful repercussions, these implanted materials are subjected to biocompatible coatings. Polymeric coatings play a vital role in enhancing the mechanical and biological integrity of the implanted devices. Zein is a natural protein extracted from corn and is known to have good bio-compatibility and biodegradability. In this study, Zein/Ag-Sr doped mesoporous bioactive glass nanoparticles (Ag-Sr MBGNs) were deposited on SS substrates via electrophoretic deposition (EPD) at different parameters. Ag and Sr ions were added to impart antibacterial and osteogenic properties to the coatings, respectively. In order to examine the surface morphology of coatings, optical microscopy and scanning electron microscopy (SEM) were performed. To analyze me-chanical strength, pencil scratch test, bend test, corrosion and wear tests were conducted on ze-in/Ag-Sr doped MBGNs coatings. The results show good adhesion strength, wettability, corro-sion, and wear resistance for zein/Ag-Sr doped MBGNs coatings as compared to bare SS sub-strate. Thus, good mechanical and biological properties were observed for zein/Ag-Sr doped MBGNs coatings. Results suggested these zein/Ag-Sr MBGNs coatings have great potential in bone regeneration applications.

Objective: Regeneration of bone defects remains a challenge for maxillofacial and reparative surgeons. The purpose of this histological study was to assess the osteogenic potential of octacalcium phosphate (OCP) and bone matrix gelatin (BMG) alone and in combination in artificially created mandibular bone defects in rats. The quality of the newly formed bone was also evaluated. Methods: Thirty-six male Sprague Dawley rats (6-8 weeks old with 120-150 g weight) were randomly divided into four groups. Defects (3 mm in diameter and 2 mm in depth) were created in the mandible of rats and filled with 6 mg of OCP, BMG or a combination of both (1/4 ratio), respectively. Defects were left unfilled in the control group. To assess osteoinduction and bone regeneration and determine the quality of the newly formed bone, tissue specimens were harvested at seven, 14, and 21 days post-implantation. The specimens were processed, stained with hematoxylin and eosin (H&E) and histologically analyzed under light microscopy. Results: In the experimental groups, new bone formation was initiated at the margins of defects from seventh day after implantation. At the end of the study period, the amount of the newly formed bone increased and the bone was relatively mature. Osteoinduction and new bone formation were greater in OCP/BMG group. In the control group, slight amount of new bone had been formed at the defect margins (next to host bone) on day 21. Conclusion: Combination of OCP/BMG may serve as an optimal biomaterial for treatment of mandibular bone defects.

Background: Scaffold (SCA) functionalization with aptamers (APT) provides adsorption of specific bioactive molecules on biomaterials surface. The aim of this study was to observe if SCA enriched with anti-fibronectin APT can favor coagulum (PhC) and osteoblasts (OSB) differentiation. Methods: 20 ug of APT was functionalized on SCA by simple adsorption. For PhC formation, SCAs were inserted into rat calvaria defects for 17 hours. Following proper transportation (Buffer solution-PB), OSB (UMR-106 lineage) were seeded over PhC + SCAs with and without APT. Cells and PhC morphology, PhC cell population, protein labelling and gene expression were observed in different time points. Results: The APT induced higher ALP and BSP immunolabeling in OSB. CD90, CD45 and CD44 expression was more detected in APT group than when scaffolds were not functionalized. Additionally, an enriched and dense fibrin network and different cell types were observed, with more OSB and white blood cells in PhC formed on SCA with APT. The gene expression showed higher TGF-β1 detection in SCA with APT. Conclusions: The SCA functionalization with fibronectin aptamers provides a selective expression of proteins related to coagulation pattern and osteo differentiation. Additionally, aptamers increase TGF-β1 gene expression, which is highly associated with improvements in regenerative therapies.

Magnesium ions play an important immune-regulatory role during bone repair. For this study, we prepared micro-nano bioactive glass containing magnesium, which can release magnesium, silicon, and calcium ions and has a positive impact on osteogenic differentiation and vascular regeneration. In this study, MgMNBG was compounded and combined with PLGA and PCL for 3D printing. Afterwards, the physicochemical properties and bone repair performance of the scaffolds were evaluated through in vitro and in vivo experiments. We also investigated the effects of MgMNBG on osteogenic differentiation, immune regulation, and vascular regeneration. The results showed that MgMNBG can inhibit inflammation and promote osteogenesis and angiogenesis by regulating macrophages. PLGA/PCL/MgMNBG scaffolds have good osteogenic and angiogenic effects, and the composite scaffolds have excellent bone repair performance and potential application value.

Bone innate ability to repair without scaring is surpassed by major bone damage. Current gold-standard strategies do not achieve a full recovery of bone biomechanical properties. To bypass these limitations, tissue engineering techniques based on hybrid materials made up of osteoprogenitor cells, like mesenchymal stem cells (MSCs), and bioactive ceramic scaffolds, like calcium phosphate-based (CaPs), are promising. Biological properties of the MSCs, are influenced by the tissue source. The aim of this study is to define the MSC source and construct (MSC and scaffold combination) most interesting for its clinical application in bone regeneration. iTRAQ generated the hypothesis that anatomical proximity to bone has a direct effect on MSC phenotype. MSCs were isolated from adipose tissue, bone marrow and dental pulp. MSCs were cultured both on plastic surface and on CaPs (hydroxyapatite and β-tricalcium phosphate) to compare their biological features. On plastic, MSCs isolated from dental pulp (DPSCs) were the MSCs with the highest proliferation capacity and the greatest osteogenic potential. On both CaPs, DPSCs are the MSCs with the greatest capacity to colonize bioceramics. Furthermore, results show a trend for DPSCs are the MSCs with the most robust increase in the ALP activity. We propose DPSCs as a suitable MSCs for bone regeneration cell-based strategies.What do you want to do ?New mailCopy

Recent interest in preventing the development of osteoporosis has focused on the regulation of redox homeostasis. However, the action of lycopene (LYC), a strong natural antioxidant com-pound, on osteoporotic bone loss remains largely unknown. Here, we show that the administra-tion of LYC to OVX rats reduces body weight gain, improves lipid metabolism and preserves bone quality. In addition, LYC treatment inhibits ROS overgeneration in serum and bone marrow in OVX rats, and in BMSCs upon H2O2 stimulation, leading to inhibiting adipogenesis and pro-moting osteogenesis during bone remodeling. Mechanically, LYC may improve bone quality via an increase in the expressions of FoxO1 and Runx2, and a decrease in the expressions of PPARγ and C/EBPα in OVX rats and BMSCs. Collectively, these findings suggest that LYC attenuates osteoporotic bone loss through promoting osteogenesis and inhibiting adipogenesis via regula-tion of the FoxO1/PPARγ pathway driven by oxidative stress, presenting a novel strategy for os-teoporosis management.

Reparative osteogenesis in the damaged vertebrae is a complex cascade of morphological and biochemical processes that result in the consolidation of the vertebral body. This research was aimed at studying the features of reparative osteogenesis in damaged thoracic and lumbar vertebral bodies at different time points after injury. We analyzed the morphological findings of the vertebral tissues harvested during surgical interventions in 43 patients with recent, subacute and long-standing injuries to thoracic and lumbar spine, and found that cell differentiation in osteogenesis is closely related to angiogenesis and the metabolic cascade. In areas with sufficient oxygenation, good partial pressure of oxygen, and active growth of microvasculature the normal cycle of development and differentiation of osteoblasts and osteocytes occurs, and hypoxia and acidosis lead to pathological osteogenesis. The reclination maneuver with dorsal tools on Day 10-12 of the injury may be ineffective due to the formation of adhesions between fragments, and reclination of the body of the damaged vertebra two weeks or more after the injury is apparently doomed to failure. Timely ventral fusion performed for objective indications is the key to successful rehabilitation of patients, on the one hand, and reduction of the surgical trauma volume in the future, on the other.

Electrospinning is the versatile technique to generate large quantities of micro- or nano-fibers from a wide variety of shapes and sizes of polymer. Natural bone is a hierarchically composites with the dispersion of inorganic ceramic along organic polymer. The aim of this study, the electrospun poly (lactic acid) (PLA) mats coated with chitosan (CH) and calcium silicate (CS) powder were fabricated. The morphology, chemical composition, and surface properties of CS/CH-PLA composites were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. In vitro, the CS/CH-coated PLA mats increased the formation of apatite on the surface when soaking in cell cultured medium. During culture, the adhesion and proliferation of the human mesenchymal stem cells (hMSCs) cultured on CS/CH-PLA were significantly promoted relative to those on PLA. Collagen I and fibronectin levels and promoted cell adhesion were observed upon an increase in CS content. Further, compared to PLA mats without CS/CH, CS10 and CS15 mats markedly enhanced the proliferation of hMSCs as well as their osteogenesis properties, which was characterized by bone-related gene expression. Our results demonstrated that the biodegradable and electroactive CS/CH-PLA mats had potential application as an ideal candidate for bone tissue engineering. Together, findings from this study clearly demonstrated that PLLA-C2S composite scaffold may function as an ideal candidate for bone tissue engineering.

There are several pathologies that can change the anatomy of the otic capsule and that can distort the bone density of the bony structures of the inner ear, but otosclerosis is one of the most frequent. Similar behavior has been shown in patients affected by osteogenesis imperfecta (OI), a genetic disease due to a mutation in the genes coding for type I (pro) collagen. In particular, we note that otosclerosis and OI can lead to bone resorption creating pericochlear cavitations in contact with the internal auditory canal (IAC). In this regard, in our experience we have collected 5 cases presenting this characteristic and their audiological data and clinical history were analyzed. This feature can be defined as a potential cause of a third-window effect, because it causes an energy loss during the transmission of sound waves from the OW away from the basilar membrane.

Matrix vesicles (MVs) are nano-sized extracellular vesicles that are anchored in the extracellular matrix (ECM). In addition to playing a role in biomineralization, osteoblast-derived MVs were recently suggested to have regulatory duties. The aims of this study were to: establish the characteristics of osteoblast-derived MVs in the context of extracellular vesicles like exosomes, assess their role in modulating osteoblast differentiation, and examine their mechanism of uptake. MVs were isolated from the ECM of MG-63 human osteoblast-like cell cultures and characterized via enzyme activity, transmission electron microscopy, nanoparticle tracking analysis, western blot, and small RNA sequencing. Osteoblasts were treated with MVs from two different culture conditions (growth media [GM]; osteogenic media [OM]) to evaluate their effects on differentiation and production of inflammatory markers and on macrophage polarization. MV endocytosis was assessed using a lipophilic, fluorescent dye and confocal microscopy with the role of caveolae determined using methyl-β-cyclodextrin. MVs exhibited a four-fold enrichment in alkaline phosphatase specific activity compared to plasma membranes, were 50-150nm in diameter, possessed exosomal markers CD63, CD81, and CD9 and endosomal markers ALIX, TSG101, and HSP70, and were selectively enriched in microRNA linked to an anti-osteogenic effect and to M2 macrophage polarization. Treatment with GM or OM MVs decreased osteoblast differentiation. Osteoblasts endocytosed MVs by a mechanism that involves caveolae. These results support the hypothesis that osteoblasts produce MVs that participate in the regulation of osteogenesis.

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.

Objectives Bone fractures are very common diseases, which can be caused by impact injuries or physiological disorders. Thus, the present review aimed to study the use of medicinal plants in the healing mechanism of bone fractures. Evidence acquisition Through research in the PubMed, Google Academic, and Scielo databases, this article reviews 11 ethnopharmacological studies and 34 preclinical studies on the biological actions of different plants in bone fracture healing mechanism. Results Indian tribes have highlighted in the plants ethnopharmacological study for various diseases, including bone fractures. However, despite the large citations of traditional use, technical-scientific studies are still scarce in the literature. Chenopodium ambrosioides, Piper sarmentosum, quadrangular Cissus, Ricinus communis and Radix salvia miltiorrhiza plants were the most studied in the literature regarding their osteogenic, angiogenic, anti-inflammatory and remodeling effects, acting on bone receptors, stimulating bone metabolism, increasing minerals uptake, and assisting in free radicals breakdown. Conclusion Thus, the medicinal plants use is promising in the field of bone regeneration, as well as being alternative when conventional therapies are unfeasible, increasing herbal medicines demand and popularity.

There is currently an interest in “active” implantable biomedical devices that include mechanical stimulation as an integral part of their design. This paper reports the experimental use of a porous scaffold made of interconnected networks of slender ferromagnetic fibres that can be actuated in vivo by an external magnetic field applying strains to in-growing cells. Such scaffolds have been previously characterized in terms of their mechanical and cellular responses. In this study, it is shown that the shape changes induced in the scaffolds can be used to promote osteogenesis in vitro. In particular, immunofluorescence, gene and protein analyses reveal that the actuated networks exhibit higher mineralization and extracellular matrix production, and express higher levels of osteocalcin, alkaline phosphatase, collagen type 1a1, runt-related transcription factor 2 and bone morphogenetic protein 2 than the static controls at the 3-week time point. The results suggest that the cells filling the inter-fibre spaces are able to sense and react to the magneto-mechanically induced strains facilitating osteogenic differentiation and maturation. This work provides evidence in support of using this approach to stimulate bone ingrowth around a device implanted in bone and can pave the way for further applications in bone tissue engineering.

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

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.

The increase in the rate and prevalence of diseases associated with the localized and general loss of bone mass calls for an investigation into therapeutic alternatives that largely involve the de-velopment of new biomaterials and cell therapy, converting tissue bioengineering into a prom-ising option. An experimental model of a critical mandibular lesion in rats has been used to study bone re-generation by treating the ostectomy with the biomaterials Evolution® and Gen-Os® (OsteoBiol®, Italy) combined, or not, with dental pulp stem cells (DP-MSC). The results obtained through the Micro-CT and histological study reveal the almost complete re-covery of the lesion in the group with DP-MSC. These results are supported by increases in endoglin, TGF-β, protocollagen I, parathormone, and calcitonin, generating an environment of bone generation and development when combining Evolution® and Gen-Os® (OsteoBiol®, Italy) with DP-MSC. These promising results confirm the transcendental role of DP-MSC in combina-tion with osteogenic biomaterials for bone regeneration, and warrant further studies, including its assessment in clinical trials.

Renewable resources gain increasing interest as source for environmentally benign biomaterials, such as drug encapsulation/release compounds, and scaffolds for tissue engineering in regenerative medicine. Being the second largest naturally abundant polymer, the interest in lignin valorization for biomedical utilization is rapidly growing. Depending on resource and isolation procedure, lignin shows specific antioxidant and antimicrobial activity. Today, efforts in research and industry are directed toward lignin utilization as renewable macromolecular building block for the preparation of polymeric drug encapsulation and scaffold materials. Within the last five years, remarkable progress has been made in isolation, functionalization and modification of lignin and lignin-derived compounds. However, literature so far mainly focuses lignin-derived fuels, lubricants and resins. The purpose of this review is to summarize the current state of the art and to highlight the most important results in the field of lignin-based materials for potential use in biomedicine (reported in 2014–2018). Special focus is drawn on lignin-derived nanomaterials for drug encapsulation and release as well as lignin hybrid materials used as scaffolds for guided bone regeneration in stem cell-based therapies.

This study examines the effect of a hyaluronic acid (HyAc) containing tricalcium phosphate putty scaffold material (TCP-P) and of a particulate tricalcium phosphate (TCP-G) graft on bone formation, volume stability and osteogenic marker expression in biopsies sampled 6 months after bilateral sinus floor augmentation (SFA) in 7 patients applying a split-mouth design. Biopsies were processed for immunohistochemical analysis of resin embedded sections. Sections were stained for collagen type I (Col I), alkaline phosphatase (ALP), osteocalcin (OC) and bone sialoprotein (BSP). Furthermore, the bone area and particle area fraction were determined histomorphometrically. Cone-beam CT data recorded after SFA and 6 month later were used for calculating the graft volume at these two time points. TCP-P displayed more advantageous surgical handling properties and a significantly greater bone area fraction and smaller particle area fraction. This was accompanied by significantly greater expression of Col I and BSP and in osteoblasts and osteoid and a less pronounced reduction in grafting volume with TCP-P. SFA using both types of materials resulted in formation of sufficient bone volume for facilitating stable dental implant placement with all dental implants having been in function without any complications for 6 years. Since TCP-P displayed superior surgical handling properties and greater bone formation than TCP-G, without the Hyac hydrogel matrix having any adverse effect on bone formation or graft volume stability, TCP-P can be regarded as excellent grafting material for SFA in a clinical setting.