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Reconstruction of bone defects, especially the critical-sized defects, with mechanical integrity to the skeleton is important for a patient's rehabilitation, however, it still remains challenge. Utilizing biomaterials of human origin bone tissue for therapeutic purposes has provided a facilitated approach that closely mimics the critical aspects of natural bone tissue with regard to its properties. However, not only efficacious and safe but also cost-effective and convenient are important for regenerative biomaterials to achieve clinical translation and commercial success. Advances in our understanding of regenerative biomaterials and their roles in new bone formation potentially opened a new frontier in the fast-growing field of regenerative medicine. Taking inspiration from the role and multicomponent construction of native extracellular matrix (ECM) for cell accommodation, the ECM-mimicking biomaterials and the naturally decellularized ECM scaffolds were used to create new tissues for bone restoration. On the other hand, with the going deep in understanding of mesenchymal stem cells (MSCs), they have shown great promise to jumpstart and facilitate bone healing even in diseased microenvironments with pharmacology-based endogenous MSCs rescue/mobilization, systemic/local infusion of MSCs for cytotherapy, biomaterials-based approaches, cell-sheets/-aggregates technology and usage of subcellular vesicles of MSCs to achieve scaffolds-free or cell-free delivery system, all of them have been shown can improve MSCs-mediated regeneration in preclinical studies and several clinical trials. Here, following an overview discussed autogenous/allogenic and ECM-based bone biomaterials for reconstructive surgery and applications of MSCs-mediated bone healing and tissue engineering to further offer principles and effective strategies to optimize MSCs-based bone regeneration., Competing Interests: The authors declare no competing financial interests., (© 2020 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Objective: To investigate the effect of the supernatant of osteoclasts during bone resorption on the proliferation and differentiation of bone marrow-derived mesenchymal stem cells (BMSCs)., Methods: Spleen cells were induced into osteoclasts which were identified with tartrate-resistant acid phosphatase (TRAP) staining. The osteoclasts were cultured with bovine bone slices and the resorption pits on the slices were observed by scanning electron microscopy. The supernatant of the osteoclasts during bone absorption were taken and added into BMSCs. MTT assay was used to analyze the growth curves of BMSCs in experimental and control groups. After adipogenic induction, lipid droplets were observed by oil red O staining to compare the adipogenic potential between the two groups. After osteogenic induction, calcium nodules were observed by alizarin red staining. The expression levels of osteogenesis-related proteins RUNX2 and alkaline phosphatase (ALP), and adipogenesis-related protein PPAR-γ were measured by Western blotting., Results: TRAP staining and scanning electron microscopy indicated that BMSCs could be differentiated into functional osteoclasts. Compared with the control group, the proliferation capacity of BMSCs in the experimental group was suppressed, the osteogenic potential was enhanced, and the adipogenic potential was weakened., Conclusion: The supernatant of osteoclasts during bone absorption might increase the osteogenic activity of BMSCs by inhibiting proliferation and adipogenesis and promoting differentiation.

Objective: To reveal the role of bone marrow-derived mesenchymal stem cells (BMSCs) in the development of osteoporosis by comparing the differences in monocyte chemoattractant protein-1 (MCP-1) expression and T cells' migration and apoptosis induced by BMSCs from ovariectomy (OVX) group and sham group., Methods: OVX was performed on C57BL/6 mice to establish the animal models of osteoporosis. Osteoporosis was confirmed by micro-CT. The expression of MCP-1 between OVX group and sham group was examined by ELISA; after exogenous estrogen of different concentrations were given to stimulate BMSCs from OVX group, the expression of MCP-1 was observed again by ELISA. Through co-culturing of BMSCs and T cells, the change of T cells' migration and apoptosis capacity induced by BMSCs was compared between OVX group and sham group. And also, we observed the effects of exogenous estrogen of different concentrations on the T cells' migration and apoptosis capacity., Results: In animal models of osteoporosis induced by estrogen deficiency, BMSCs had a declined inducing effect on the capacity of T cell migration and apoptosis and expressed a decreased level of migration-related gene MCP-1. After the stimulation of estrogen of certain concentration, the declining tendency was revised to some extent., Conclusion: Through expressing MCP-1, BMSCs could regulate the capacity of T cell migration and apoptosis, thus leading to the development of osteoporosis.

Objective: To investigate the therapeutic effects of bone marrow-derived mesenchymal stem cells (BMSCs) from C57BL/6 mice on estrogen deficiency induced osteoporosis., Methods: Mouse models of estrogen deficiency induced osteoporosis were set up through ovariectomy (OVX) operation and sham operation group was set up as controls. BMSCs were injected via caudal veins. Micro-CT scanning of the femurs was conducted to detect the therapeutic effects of BMSCs. ELISA was used to test the expression level of TNF-α in serum before and after the injection of BMSCs. In the meantime, T cell apoptosis was also tested by flow cytometry combined with FITC-annexin V/7-amino actimycin D staining., Results: Compared with the sham operation group, the trabecular volume (BV/TV), bone mineral density (BMD) and trabecular number (Tb.N/mm) of osteoporosis mice set up by OVX were reduced significantly, and serum TNF-α was up-regulated a little. After the injection of BMSCs, the BV/TV, Tb.Th, Tb.N and T cell apoptosis in the osteoporosis mice increased, and the level of TNF-α decreased., Conclusion: With the ability of immunoregulation, BMSCs might play a critical role in treating estrogen deficiency induced osteoporosis.

Objective: To investigate the difference in the therapeutic effects of bone marrow-derived mesenchymal stem cells (BMSCs) of mice from ovariectomy (OVX) group and sham group in treating colitis, and then further study the differences of Fas/FasL expression and downstream T cell migration and apoptosis between the two groups., Methods: The osteoporosis animal models were set up by ovariectomy in C57BL6 mice. Meanwhile, 3% dextran sulfate sodium (DSS) was administered for inducing colitis. We compared the therapeutic effects of BMSCs from OVX and sham groups in treating colitis, in addition, detected the expression of Fas/FasL in BMSCsby means of RT-PCR and Western blotting. The ability of BMSCs from the two groups of inducing T cell migaration and apoptosis was also detected., Results: Compared with the sham group, BMSCs from OVX mice expressed a lower level of Fas/FasL and displayed a decreased ability of inducing T cell migration and apoptosis, thus leading to an inferior therapeutic effect in treating colitis in animal models., Conclusion: Fas/FasL expression of BMSCs from the OVX mice is down regulated, thus leading to a decrease of the migration and apoptosis for T cells from mouse colitis.