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Bone regeneration is essential for treating critically sized bone defects, which are challenging to restore naturally. The traditional methods like autogenous bone grafting have limitations, prompting research into alternative materials such as demineralized bone matrix (DBM). While bovine and porcine DBMs are common, they have stability and safety concerns, leading to the exploration of poultry-derived DBPs. The study aimed to fabricate scaffolds using DBPs from different poultry species and compare their effectiveness in bone regeneration. DBPs were extracted from the femurs and tibias of chickens, ducks, and Yeonsan ogolgye (Gallus gallus domesticus Brisson). These DBPs were used to create sponges, which were then characterized for their physical and chemical properties. The bone marrow-derived stem cells (rBMSCs) from rabbits were seeded onto these sponges to evaluate their biocompatibility and bone regeneration potential in vitro. The sponges were porous, facilitating cell infiltration and nutrient exchange, with different compressive strengths and porosity levels based on the poultry source. The sponges supported cell proliferation, with the Yeonsan ogolgye-derived sponge (GDS) showing the highest levels of osteogenic markers, likely due to its melanin content, which enhances bone growth factors. The study found that all sponges were biocompatible, with the GDS being the most effective in promoting bone regeneration. Poultry-derived DBP sponges, especially those from Yeonsan ogolgye, are promising candidates for bone graft materials due to their favorable properties in supporting bone regeneration. [ABSTRACT FROM AUTHOR]

The repair of critical-sized calvarial defects is a challenging problem for orthopedic surgery. One of the promising strategies of bone bioengineering to enhance the efficacy of large bone defect regeneration is the combined delivery of stem cells with osteoinductive factors within polymer carriers. The purpose of the research was to study the regenerative effects of heparin-conjugated fibrin (HCF) hydrogel containing bone morphogenetic protein 2 (BMP-2) and adipose-derived pericytes (ADPs) in a rat critical-sized calvarial defect model. In vitro analysis revealed that the HCF hydrogel was able to control the BMP-2 release and induce alkaline phosphatase (ALP) activity in neonatal rat osteoblasts. In addition, it was found that eluted BMP-2 significantly induced the osteogenic differentiation of ADPs. It was characterized by the increased ALP activity, osteocalcin expression and calcium deposits in ADPs. In vivo studies have shown that both HCF hydrogel with BMP-2 and HCF hydrogel with pericytes are able to significantly increase the regeneration of critical-sized calvarial defects in comparison with the control group. Nevertheless, the greatest regenerative effect was found after the co-delivery of ADPs and BMP-2 into a critical-sized calvarial defect. Thus, our findings suggest that the combined delivery of ADPs and BMP-2 in HCF hydrogel holds promise to be applied as an alternative biopolymer for the critical-sized bone defect restoration. [ABSTRACT FROM AUTHOR]

The treatment of critical‐sized bone defects has long been a major problem for surgeons. In this study, an intramedullary nail shaped three‐dimensional (3D)‐printed porous titanium implant that is capable of releasing strontium ions was developed through a simple and cost‐effective surface modification technique. The feasibility of this implant as a stand‐alone solution was evaluated using a rabbit's segmental diaphyseal as a defect model. The strontium‐loaded implant exhibited a favorable environment for cell adhesion, and mechanical properties that were commensurate with those of a rabbit's cortical bone. Radiographic, biomechanical, and histological analyses revealed a significantly higher amount of bone ingrowth and superior bone‐bonding strength in the strontium‐loaded implant when compared to an untreated porous titanium implant. Furthermore, one‐year histological observations revealed that the strontium‐loaded implant preserved the native‐like diaphyseal bone structure without failure. These findings suggest that strontium‐releasing 3D‐printed titanium implants have the clinical potential to induce the early and efficient repair of critical‐sized, load‐bearing bone defects. [ABSTRACT FROM AUTHOR]

The scarcity of native periosteum poses a significant clinical barrier in the repair of critical-sized bone defects. The challenge of enhancing regenerative potential in bone healing is further compounded by oxidative stress at the fracture site. However, the introduction of artificial periosteum has demonstrated its ability to promote bone regeneration through the provision of appropriate mechanical support and controlled release of pro-osteogenic factors. In this study, a poly (l -lactic acid) (PLLA)/hyaluronic acid (HA)-based nanofibrous membrane was fabricated using the coaxial electrospinning technique. The incorporation of irisin into the core-shell structure of PLLA/HA nanofibers (PLLA/HA@Irisin) achieved its sustained release. In vitro experiments demonstrated that the PLLA/HA@Irisin membranes exhibited favorable biocompatibility. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) was improved by PLLA/HA@Irisin, as evidenced by a significant increase in alkaline phosphatase activity and matrix mineralization. Mechanistically, PLLA/HA@Irisin significantly enhanced the mitochondrial function of BMMSCs via the activation of the sirtuin 3 antioxidant pathway. To assess the therapeutic effectiveness, PLLA/HA@Irisin membranes were implanted in situ into critical-sized calvarial defects in rats. The results at 4 and 8 weeks post-surgery indicated that the implantation of PLLA/HA@Irisin exhibited superior efficacy in promoting vascularized bone formation, as demonstrated by the enhancement of bone matrix synthesis and the development of new blood vessels. The results of our study indicate that the electrospun PLLA/HA@Irisin nanofibers possess characteristics of a biomimetic periosteum, showing potential for effectively treating critical-sized bone defects by improving the mitochondrial function and maintaining redox homeostasis of BMMSCs. [ABSTRACT FROM AUTHOR]

In craniofacial bone defects, the promotion of bone volume augmentation remains a challenge. Finding strategies for bone regeneration such as combining resorbable minerals with organic polymers would contribute to solving the bone volume roadblock. Here, dicalcium phosphate dihydrate, chitosan and hyaluronic acid were used to functionalize a bone-side collagen membrane. Despite an increase in the release of inflammatory mediators by human circulating monocytes, the in vivo implantation of the functionalized membrane allowed the repair of a critical-sized defect in a calvaria rat model with de novo bone exhibiting physiological matrix composition and structural organization. Microtomography, histological and Raman analysis combined with nanoindentation testing revealed an increase in bone volume in the presence of the functionalized membrane and the formation of woven bone after eight weeks of implantation; these data showed the potential of dicalcium phosphate dihydrate, chitosan and hyaluronic acid to induce an efficient repair of critical-sized bone defects and establish the importance of thorough multi-scale characterization in assessing biomaterial outcomes in animal models. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu is the property of Chinese Journal of Tissue Engineering Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Repair of large-sized bone defects is a challengeable obstacle in orthopedics and evoked the demand for the development of biomaterials that could induce bone repair in such defects. Recently, UiO-66 has emerged as an attractive metal–organic framework (MOF) nanostructure that is incorporated in biomedical applications due to its biocompatibility, porosity, and stability. In addition, its osteogenic properties have earned a great interest as a promising field of research. Thus, the UiO-66 was prepared in this study and assessed for its potential to stimulate and support osteogenesis in vitro and in vivo in a rabbit femoral condyle defect model. The nanomaterial was fabricated and characterized using x-ray diffraction (XRD) and transmission electron microscopy (TEM). Afterward, in vitro cytotoxicity and hemolysis assays were performed to investigate UiO-66 biocompatibility. Furthermore, the material in vitro capability to upregulate osteoblast marker genes was assessed using qPCR. Next, the in vivo new bone formation potential of the UiO-66 nanomaterial was evaluated after induction of bone defects in rabbit femoral condyles. These defects were left empty or filled with UiO-66 nanomaterial and monitored at weeks 4, 8, and 12 after bone defect induction using x-ray, computed tomography (CT), histological examinations, and qPCR analysis of osteocalcin (OC) and osteopontin (OP) expressions. Results: The designed UiO-66 nanomaterial showed excellent cytocompatibility and hemocompatibility and stimulated the in vitro osteoblast functions. The in vivo osteogenesis was enhanced in the UiO-66 treated group compared to the control group, whereas evidence of healing of the treated bone defects was observed grossly and histologically. Interestingly, UiO-66 implanted defects displayed a significant osteoid tissue and collagen deposition compared to control defects. Moreover, the UiO-66 nanomaterial demonstrated the potential to upregulate OC and OP in vivo. Conclusions: The UiO-66 nanomaterial implantation possesses a stimulatory impact on the healing process of critical-sized bone defects indicating that UiO-66 is a promising biomaterial for application in bone tissue engineering. [ABSTRACT FROM AUTHOR]

Copyright of Orthopaedics, Traumatology & Prosthetics / Ortopediia, Traumatologiia i Protezirovaniie is the property of Orthopaedics, Traumatology & Prosthetics / Ortopediia, Traumatologiia i Protezirovaniie and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In vivo bioreactors serve as regenerative niches that improve vascularization and regeneration of bone grafts. This study has evaluated the masseter muscle as a natural bioreactor for βTCP or PCL/βTCP scaffolds, in terms of bone regeneration. The effect of pedicle preservation, along with sole, or MSC‐ or rhBMP2‐combined application of scaffolds, has also been studied. Twenty‐four mongrel dogs were randomly placed in six groups, including βTCP, βTCP/rhBMP2, βTCP/MSCs, PCL/βTCP, PCL/βTCP/rhBMP2, and PCL/βTCP/MSCs. During the first surgery, the scaffolds were implanted into the masseter muscle for being prefabricated. After 2 months, each group was divided into two subgroups prior to mandibular bone defect reconstruction; one with a preserved vascularized pedicle and one without. After 12 weeks, animals were euthanized, and new bone formation was evaluated using histological analysis. Histological analysis showed that all β‐TCP scaffold groups had resulted in significantly greater rates of new bone formation, either with a pedicle surgical approach or non‐pedicle surgical approach, comparing to their parallel groups of βTCP/PCL scaffolds (p ≤.05). Pedicled β‐TCP scaffold groups that were treated with either rhBMP2 (48.443% ± 0.250%) or MSCs (46.577% ± 0.601%) demonstrated the highest rates of new bone formation (p ≤.05). Therefore, masseter muscle can be used as a local in vivo bioreactor with potential clinical advantages in reconstruction of human mandibular defects. In addition, scaffold composition, pedicle preservation, and treatment with MSCs or rhBMP2, influence new bone formation and scaffold degradation rates in the prefabrication technique. [ABSTRACT FROM AUTHOR]

Although autogenous bone grafts are an optimal filling material for the induced membrane technique, limited availability and complications at the harvest site have created a need for alternative graft materials. We aimed to investigate the effect of an rhBMP‐2‐coated, 3D‐printed, macro/microporous CaO–SiO2–P2O5–B2O3 bioactive ceramic scaffold in the treatment of critical femoral bone defects in rabbits using the induced membrane technique. A 15‐mm segmental bone defect was made in the metadiaphyseal area of the distal femur of 14 rabbits. The defect was filled with polymethylmethacrylate cement and stabilized with a 2.0 mm locking plate. After the membrane matured for 4 weeks, the scaffold was implanted in two randomized groups: Group A (3D‐printed bioceramic scaffold) and Group B (3D‐printed, bioceramic scaffold with rhBMP‐2). Eight weeks after implantation, the radiographic assessment showed that the healing rate of the defect was significantly higher in Group B (7/7, 100%) than in Group A (2/7, 29%). The mean volume of new bone formation around and inside the scaffold doubled in Group B compared to that in Group A. The mean static and dynamic stiffness were significantly higher in Group B. Histological examination revealed newly formed bone in both groups. Extensive cortical bone formation along the scaffold was found in Group B. Successful bone reconstruction in critical‐sized bone defects could be obtained using rhBMP‐2‐coated, 3D‐printed, macro/microporous bioactive ceramic scaffolds. This grafting material demonstrated potential as an alternative graft material in the induced membrane technique for reconstructing critical‐sized bone defects. [ABSTRACT FROM AUTHOR]

Several synthetic and natural scaffolds have been developed for bone tissue engineering (BTE). This study was designed to fabricate and characterize a composite scaffold based on poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV)/polycaprolactone (PCL) polymers containing 5 % Hydroxyapatite (HA) nano-particles (HA5) for regeneration of bone critical size defect in a rat animal model. In the first step of this study, the PHBV/PCL (30 and 70 wt.%, respectively) with and without HA nanoparticle scaffolds were fabricated by Dual-Leaching Technique and then evaluated for FTIR spectroscopy, SEM, degradation rate, cell binding and proliferation. In the second step, the scaffolds were applied for cell differentiation and animal study. Human osteoblast-like Saos-2 cell line was seeded onto the scaffolds and Alkaline Phosphatase (ALP) activity was assayed on 7 days and 14 post-culture. The capacity of scaffolds to promote the bone regeneration genes was also investigated using quantitative RT-PCR. The critical size defects were made on the dorsal part of the rat's calvarium and were filled with PCL70PHBV30 and PCL70PHBV30HA5 scaffolds and were then evaluated histologically and histomorphometrically. The higher mean percentage of new bone formation, bone cells and osteon, as well as lower fibrous connective tissue, was detected in the PCL70PHBV30HA5 group than that of the other groups. In conclusion, the HA nanoparticles at 5 % concentration have been well distributed in the PCL70PHBV30 scaffold that could accelerate bone regeneration. [ABSTRACT FROM AUTHOR]

Introduction: The management of acquired long bone defects (LBDs) is a persistent problem in modern orthopedics with few effective solutions. The goal of this review is to conduct a thorough analysis of existing diaphyseal LBD classifications and to identify if any of these may be adopted for universal application in future. Materials and Methods: A literature review was performed analyzing articles between 1970 and 2019 on PubMed (English) and CyberLeninka (Russian) databases. All studies developing or utilizing a classification tool were eligible for inclusion. The search retrieved a total of 1032 articles from PubMed, 477 from CyberLennika, and 28 articles from reference lists. Any disagreement regarding the inclusion of articles was resolved by consensus between all authors. Results: A total of 18 classifications in the literature underwent analysis. Among the classifications we analyzed, 12 described posttraumatic defects, 6 described osteomyelitis defects or infected nonunions, and 5 described, among other defects, iatrogenic bone. Of the 18 classifications, 12 have a focus on a specific treatment method. We found that consensus exists between most authors regarding the criteria necessary to measure to determine the most appropriate treatment method. These key factors include the size and location of the bone defect. Conclusion: This analysis showed that despite the large number of publications devoted to the classification and treatment of LBD, there is still no consensus among authors regarding not only a universal clinical classification but also a general definition of the term "bone defect." The classification proposed by Solomin et al. is very useful but in its present form, has significant drawbacks and requires further improvement before it can be adopted as a universal classification system for LBDs. [ABSTRACT FROM AUTHOR]

Background: Due to their multilineage potential and high proliferation rate, mesenchymal stem cells (MSC) indicate a sufficient alternative in regenerative medicine. In comparison to the commonly used 2-dimensional culturing method, culturing cells as spheroids stimulates the cell-cell communication and mimics the in vivo milieu more accurately, resulting in an enhanced regenerative potential. To investigate the osteoregenerative potential of MSC spheroids in comparison to MSC suspensions, cell-loaded fibrin gels were implanted into murine critical-sized femoral bone defects.Methods: After harvesting MSCs from 4 healthy human donors and preculturing and immobilizing them in fibrin gel, cells were implanted into 2 mm murine femoral defects and stabilized with an external fixator. Therefore, 26 14- to 15-week-old nu/nu NOD/SCID nude mice were randomized into 2 groups (MSC spheroids, MSC suspensions) and observed for 6 weeks. Subsequently, micro-computed tomography scans were performed to analyze regenerated bone volume and bone mineral density. Additionally, histological analysis, evaluating the number of osteoblasts, osteoclasts and vessels at the defect side, were performed. Statistical analyzation was performed by using the Student's t-test and, the Mann-Whitney test. The level of significance was set at p = 0.05.Results: μCT-analysis revealed a significantly higher bone mineral density of the MSC spheroid group compared to the MSC suspension group. However, regenerated bone volume of the defect side was comparable between both groups. Furthermore, no significant differences in histological analysis between both groups could be shown.Conclusion: Our in vivo results reveal that the osteo-regenerative potential of MSC spheroids is similar to MSC suspensions. [ABSTRACT FROM AUTHOR]

Background: The healing of large critical-sized bone defects remains a clinical challenge in modern orthopedic medicine. The current gold standard for treating critical-sized bone defects is autologous bone graft; however, it has critical limitations. Bone tissue engineering has been proposed as a viable alternative, not only for replacing the current standard treatment, but also for producing complete regeneration of bone tissue without complex surgical treatments or tissue transplantation. In this study, we proposed a transplantable radially patterned scaffold for bone regeneration that was defined by capillary force lithography technology using biodegradable polycaprolactone polymer. Results: The radially patterned transplantable biodegradable scaffolds had a radial structure aligned in a central direction. The radially aligned pattern significantly promoted the recruitment of host cells and migration of osteoblasts into the defect site. Furthermore, the transplantable scaffolds promoted regeneration of critical-sized bone defects by inducing cell migration and differentiation. Conclusions: Our findings demonstrated that topographically defined radially patterned transplantable biodegradable scaffolds may have great potential for clinical application of bone tissue regeneration. [ABSTRACT FROM AUTHOR]

Introduction: The current 'gold-standard' treatment of critical-sized bone defects (CSBDs) is autografts; however, they have drawbacks including lack of massive bone source donor site morbidity, incomplete remodeling, and the risk of infection. One potential treatment for treating CSBDs is bone marrow-derived mesenchymal stem cells (BM-MSCs). Previously, there were no studies regarding the use of human umbilical cord-mesenchymal stem cells (hUC-MSCs) for treating BDs. We aim to investigate the use of allogeneic hUC-MSCs for treating CSBDs. Method: We included subjects who were diagnosed with non-union fracture with CSBDs who agreed to undergo hUC-MSCs implantation. All patients were given allogeneic hUC-MSCs. All MSCs were obtained and cultured using the multiple-harvest explant method. Subjects were evaluated functionally using the Lower Extremity Functional Scale (LEFS) and radiologically by volume defect reduction. Result: A total of seven (3 male, 4 female) subjects were recruited for this study. The subjects age ranged from 14 to 62 years. All seven subjects had increased LEFS during the end of the follow-up period, indicating improved functional ability. The follow-up period ranged from 12 to 36 months. One subject had wound dehiscence and infection, and two subjects developed partial union. Conclusion: Umbilical cord mesenchymal stem cells are a potential new treatment for CSBDs. Additional studies with larger samples and control groups are required to further investigate the safety and efficacy of umbilical cord-derived mesenchymal stem cells for treating CSBDs. [ABSTRACT FROM AUTHOR]

Background: Critical-sized bone defects, mainly from trauma, infection or tumor resection are a challenging condition, often resulting in prolonged, complicated course of treatment. Autografts are considered as the gold standard to replace lost bone. However, limited amount of bone graft volume and donor-site morbidity have established the need for the development of alternative methods such as scaffold-based tissue engineering (TE). The emerging market of additive manufacturing (3D-printing) has markedly influenced the manufacturing of scaffolds out of a variety of biodegradable materials. Particularly medical-grade polycaprolactone and tricalcium phosphate (mPCL–TCP) scaffolds show appropriate biocompatibility and osteoconduction with good biomechanical strength in large preclinical animal models. This case report aims to show first evidence of the feasibility, safety, and efficacy of mPCL–TCP scaffolds applied in a patient with a long bone segmental defect. Case presentation: The presented case comprises a 29-year-old patient who has suffered a left-sided II° open femoral shaft fracture. After initial external fixation and subsequent conversion to reamed antegrade femoral nailing, the patient presented with an infection in the area of the formerly open fracture. Multiple revision surgeries followed to eradicate microbial colonization and attempt to achieve bone healing. However, 18 months after the index event, still insufficient diaphyseal bone formation was observed with circumferential bony defect measuring 6 cm at the medial and 11 cm at the lateral aspect of the femur. Therefore, the patient received a patient-specific mPCL–TCP scaffold, fitting the exact anatomical defect and the inserted nail, combined with autologous bone graft (ABG) harvested with the Reamer–Irrigator–Aspirator system (RIA—Synthes®) as well as bone morphogenetic protein-2 (BMP-2). Radiographic follow-up 12 months after implantation of the TE scaffold shows advanced bony fusion and bone formation inside and outside the fully interconnected scaffold architecture. Conclusion: This case report shows a promising translation of scaffold-based TE from bench to bedside. Preliminary evidence indicates that the use of medical-grade scaffolds is safe and has the potential to improve bone healing. Further, its synergistic effects when combined with ABG and BMP-2 show the potential of mPCL–TCP scaffolds to support new bone formation in segmental long bone defects. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate whether porous beads with a leaf-stacked scaffold loaded with bone morphogenetic protein-2, with sustained release for up to four weeks, were beneficial to a dog model of critical long bone defects and capable of promoting bone regeneration without side effects. Critical long bone defects were created in the femoral diaphyses of 21 dogs. Each critical defect was fixed with an intramedullary pin and an universal locking plate. Leaf-stacked scaffold beads were implanted into the defect, which was covered with a membrane. Nineteen samples were evaluated 4, 8, and 12 weeks after surgery using simple radiographs, serum chemistry measurements, histological staining, and gene expression analysis. Sustained bone morphogenetic protein-2 release from the leaf-stacked scaffold continued for four weeks and consistently affected the expression of early and late osteogenesis factors. The results suggest that sustained bone morphogenetic protein-2 release is effective for bone regeneration, with minimal side effects. [ABSTRACT FROM AUTHOR]

Introduction: Critical-sized defect (CSD) is one of the most challenging cases for orthopaedic surgeons. We aim to explore the therapeutic potential of the combination of bone marrow-derived mesenchymal stem cells (BM-MSCs), hydroxyapatite (HA) granules, bone morphogenetic protein-2 (BMP-2), and internal fixation for treating CSDs.Methods: This was a translational study performed during the period of January 2012 to 2016. Subjects were patients diagnosed with CSDs who had previously failed surgical attempts. They were treated with the combination of autologous BM-MSCs, HA granules, BMP-2, and mechanical stabilization. Post-operative pain level, functional outcome, defect volume, and radiological healing were evaluated after a minimum follow-up of 12 months.Results: A total of six subjects were recruited in this study. The pain was significantly reduced in all cases; with the decrease of mean preoperative visual analog scale (VAS) from 4 ± 2.2 to 0 after six month follow-up. Clinical functional outcome percentage increased significantly from 25 ± 13.7 to 70.79 ± 19.5. Radiological healing assessment using Tiedemann score also showed an increase from 0.16 ± 0.4 to 8 ± 3 at one year follow-up. No immunologic nor neoplastic side effects were found.Conclusions: The combination of autologous BM-MSCs, HA granules, and BMP-2 is safe and remains to be a good option for the definitive treatment for CSD with previous failed surgical attempts. Further studies with a larger sample size are required to be done. [ABSTRACT FROM AUTHOR]

Icariin, a typical flavonol glycoside, is the main active component of Herba Epimedii, which was used to cure bone-related diseases in China for centuries. It has been reported that Icariin can be delivered locally by biomaterials and it has an osteogenic potential for bone tissue engineering. Biomimetic calcium phosphate (BioCaP) bone substitute is a novel drug delivery carrier system. Our study aimed to evaluate the osteogenic potential when Icariin was internally incorporated into the BioCaP granules. The BioCaP combined with Icariin and bone morphogenetic protein 2 (BMP-2) was investigated in vitro using an MC3T3-E1 cell line. We also investigated its efficacy to repair 8 mm diameter critical size bone defects in the skull of SD male rats. BioCaP was fabricated according to a well-established biomimetic mineralization process. In vitro , the effects of BioCaP alone or BioCaP with Icariin and/or BMP-2 on cell proliferation and osteogenic differentiation of MC3T3-E1 cells were systematically evaluated. In vivo , BioCaP alone or BioCaP with Icariin and/or BMP-2 were used to study the bone formation in a critical-sized bone defect created in a rat skull. Samples were retrieved for Micro-CT and histological analysis 12 weeks after surgery. The results indicated that BioCaP with or without the incorporation of Icariin had a positive effect on the osteogenic differentiation of MC3T3-E1. BioCaP with Icariin had better osteogenic efficiency, but had no influence on cell proliferation. BioCap + Icariin + BMP-2 showed better osteogenic potential compared with BioCaP with BMP-2 alone. The protein and mRNA expression of alkaline phosphatase and osteocalcin and mineralization were higher as well. In vivo , BioCaP incorporate internally with both Icariin and BMP-2 induced significantly more newly formed bone than the control group and BioCaP with either Icariin or BMP-2 did. Micro-CT analysis revealed that no significant differences were found between the bone mineral density induced by BioCaP with icariin and that induced by BioCaP with BMP-2. Therefore, co-administration of Icariin and BMP-2 was helpful for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Background/Aims: Human dental pulp-derived mesenchymal stromal cells (hDPSCs) are promising seed cells for tissue engineering due to their easy accessibility and multilineage differentiation. Pannexin3 (Panx3) plays crucial roles during bone development and differentiation. The aim of the present study was to investigate the effect of Panx3 on osteogenesis of hDPSCs and the underlying mechanism. Methods: Utilizing qRT-PCR, Western blot, and immunohistochemistry, we explored the change of Panx3 during osteogenic differentiation of hDPSCs. Next, hDPSCs with loss (Panx3 knockdown) and gain (Panx3 overexpression) of Panx3 function were developed to investigate the effects of Panx3 on osteogenic differentiation of hDPSC and the underlying mechanism. Finally, a commercial β-TCP scaffold carrying Panx3-modified hDPSCs was utilized to evaluate bone defect repair. Results: Panx3 was upregulated during osteogenic differentiation in a time-dependent manner. Panx3 overexpression promoted osteogenic differentiation of hDPSCs, whereas depletion of Panx3 resulted in a decline of differentiation, evidenced by upregulated expression of mineralization-related markers, increased alkaline phosphatase (ALP) activity, and enhanced ALP and Alizarin red staining. Panx3 was found to interact with the Wnt/β-catenin signaling pathway, forming a negative feedback loop. However, Wnt/β-catenin did not contribute to enhancement of osteogenic differentiation as observed in Panx3 overexpression. Moreover, Panx3 promoted osteogenic differentiation of hDPSCs via increasing ERK signaling pathway. Micro-CT and histological staining results showed that Panx3-modified hDPSCs significantly improved ossification of critical-sized bone defects. Conclusion: These findings suggest that Panx3 is a crucial modulator of hDPSCs differentiation. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) can be differentiated into an osteoblastic lineage in the presence of growth factors (GFs). Platelet-rich plasma (PRP), which can be easily isolated from whole blood, contains a large amount of GFs, and, therefore, promotes bone growth and regeneration. The main goal of this work was to develop and investigate the effect of a new sandwich-like bone scaffold which combines a nano-calcium sulfate (nCS) disc along with PRP fibrin gel (nCS/PRP) with BMP2-modified MSCs on bone repair and regeneration in rat critical-sized calvarial defects. Methods: We evaluated the cytotoxicity, osteogenic differentiation and mineralization effect of PRP extract on BMP2-modified MSCs and constructed a sandwich-like nCS/PRP scaffold (mimicking the nano-calcium matrix of bone and carrying multi GFs in the PRP) containing BMP2-modified MSCs. The capacity of this multifunctional bone regeneration system in promoting bone repair was assessed in vivo in a rat critical-sized (8 mm) calvarial bone defect model. Results: We developed an optimized nCS/PRP sandwich-like scaffold. Scanning electron microscopy (SEM) results showed that nCS/PRP are polyporous with an average pore diameter of 70-80 µm and the cells can survive in the nCS/PRP scaffold. PRP extract dramatically stimulated proliferation and differentiation of BMP2-modified MSCs in vitro. Our in vivo results showed that the combination of BMP2-modified MSCs and nCS/PRP scaffold dramatically increased new bone regeneration compared with the groups without PRP and/or BMP2. Conclusions: nCS/PRP scaffolds containing BMP2-modified MSCs successfully promotes bone regeneration in critical-sized bone defects. This system could ultimately enable clinicians to better reconstruct the craniofacial bone and avoid donor site morbidity for critical-sized bone defects. [ABSTRACT FROM AUTHOR]

A three-dimensional porous nano-hydroxyapatite (nHA)/chitosan (CS) biocomposite was synthesized. The rod-like nHA grains of 15—30 × 5—10 nm in size were observed by TEM and confirmed by characteristic XRD patterns. The diameters of the interconnecting pores of the nHA/CS biocomposite, determined by SEM, were 120—300 μm. Standard critical-sized calvarial bone defect ( = 6.5 mm) was created in Sprague-Dawley (SD) rats. In group 1, nHA/CS was implanted and in group 2, no implant was made in the defect. After 1 week, the histological assessment of group 1 clearly showed that a large number of living cells were anchored in the pores of the nHA/CS implants. New bone formation, both at the edge and in the center of implants, was found as early as 2 weeks. Histological assays confirmed that the newly formed bone tissue was bioactive and neovascularized. After 5 weeks, the mineral content and volume of the newly formed bone tissue in the defects were significantly greater in group 1 than in group 2 (p < 0.01). These results indicate that implantation of the nHA/CS enhanced the repair of bone defect and confirm the potential of this biocomposite as a bioactive bone grafting substitute. [ABSTRACT FROM PUBLISHER]

Difficulties in treating pseudarthrosis and critical bone defects are still evident in physicians' clinical routines. Bone morphogenetic protein 2 (BMP-2) has shown promising osteoinductive results but also considerable side effects, not unexpected given that it is a morphogen. Thus, the bone regenerative potential of the novel selective, non-morphogenic EP4 prostaglandin receptor agonist KMN-159 was investigated in this study. Therefore, mineralized collagen type-1 matrices were loaded with different amounts of BMP-2 or KMN-159 and implanted into a 5 mm critical-sized femoral defect in rats. After 12 weeks of observation, micro-computed tomography scans were performed to analyze the newly formed bone volume (BV) and bone mineral density (BMD). Histological analysis was performed to evaluate the degree of defect healing and the number of vessels, osteoclasts, and osteoblasts. Data were evaluated using Kruskal-Wallis followed by Dunn's post hoc test. As expected, animals treated with BMP-2, the positive control for this model, showed a high amount of newly formed BV as well as bone healing. For KMN-159, a dose-dependent effect on bone regeneration could be observed up to a dose optimum, demonstrating that this non-morphogenic mechanism of action can stimulate bone formation in this model system. [ABSTRACT FROM AUTHOR]

Bioceramic scaffolds are appealing for alveolar bone regeneration, because they are emerging as promising alternatives to autogenous and heterogenous bone grafts. The aim of this systematic review is to answer to the focal question: in critical-sized bone defects in experimental animal models, does the use of a bioceramic scaffolds improve new bone formation, compared with leaving the empty defect without grafting materials or using autogenous bone or deproteinized bovine-derived bone substitutes? Electronic databases were searched using specific search terms. A hand search was also undertaken. Only randomized and controlled studies in the English language, published in peer-reviewed journals between 2013 and 2018, using critical-sized bone defect models in non-medically compromised animals, were considered. Risk of bias assessment was performed using the SYRCLE tool. A meta-analysis was planned to synthesize the evidence, if possible. Thirteen studies reporting on small animal models (six studies on rats and seven on rabbits) were included. The calvarial bone defect was the most common experimental site. The empty defect was used as the only control in all studies except one. In all studies the bioceramic materials demonstrated a trend for better outcomes compared to an empty control. Due to heterogeneity in protocols and outcomes among the included studies, no meta-analysis could be performed. Bioceramics can be considered promising grafting materials, though further evidence is needed. [ABSTRACT FROM AUTHOR]