Large bone defects are serious complications that are most commonly caused by extensive trauma, tumour, infection, or congenital musculoskeletal disorders. If nonunion occurs, implantation for repairing bone defects with biomaterials developed as a defect filler, which can promote bone regeneration, is essential. In order to evaluate biomaterials to be developed as bone substitutes for bone defect repair, it is essential to establish clinically relevant in vitro and in vivo testing models for investigating their biocompatibility, mechanical properties, degradation, and interactional with culture medium or host tissues. The results of the in vitro experiment contribute significantly to the evaluation of direct cell response to the substitute biomaterial, and the in vivo tests constitute a step midway between in vitro tests and human clinical trials. Therefore, it is essential to develop or adopt a suitable in vivo bone defect animal model for testing bone substitutes for defect repair. This review aimed at introducing and discussing the most available and commonly used bone defect animal models for testing specific substitute biomaterials. Additionally, we reviewed surgical protocols for establishing relevant preclinical bone defect models with various animal species and the evaluation methodologies of the bone regeneration process after the implantation of bone substitute biomaterials. This review provides an important reference for preclinical studies in translational orthopaedics.

The treatment of bone defects remains a significant challenge to be solved clinically. Immunomodulatory properties of orthopedic biomaterials have significance in regulating osteoimmune microenvironment for osteogenesis. A lactic acid‐co‐glycolic acid (PLGA) scaffold incorporates black phosphorus (BP) fabricated by 3D printing technology to investigate the effect of BP on osteoimmunomodulation and osteogenesis in site. The PLGA/BP scaffold exhibits suitable biocompatibility, biodegradability, and mechanical properties as an excellent microenvironment to support new bone formation. The studies' result also demonstrate that the PLGA/BP scaffolds are able to recruit and stimulate macrophages M2 polarization, inhibit inflammation, and promote human bone marrow mesenchymal stem cells (hBMSCs) proliferation and differentiation, which in turn promotes bone regeneration in the distal femoral defect region of steroid‐associated osteonecrosis (SAON) rat model. Moreover, it is screened and demonstrated that PLGA/BP scaffolds can promote osteogenic differentiation by transcriptomic analysis, and PLGA/BP scaffolds promote osteogenic differentiation and mineralization by activating PI3K‐AKT signaling pathway in hBMSC cells. In this study, it is shown that the innovative PLGA/BP scaffolds are extremely effective in stimulating bone regeneration by regulating macrophage M2 polarization and a new strategy for the development of biomaterials that can be used to repair bone defects is offered.

Magnesium (Mg) or its alloys are widely tested as potential orthopedic implants, particularly as biodegradable alloys for fracture fixation due to their mechanical properties are close to those of bone. Currently, available Mg or its alloys are confronted with challenges in passing regulatory biosafety tests prior to clinical trials due to its fast degradation and associated degradation products. The degradation of Mg is accompanied by the release of Mg ions, the rise of pH and osmolality in surrounding environments. According to the standard of ISO 10993 Part 13, the pH value shall be appropriate to the site of intended use maintaining in an appropriate range. Approaches to overcome these challenges include the selection of adequate alloying elements, proper surface treatment techniques and control of the degradation rate of Mg or its alloys developed as orthopedic implants. To date, Mg or its alloy-based bone implants have not yet been widely used in clinical applications as medical implants. This review critically summarized published methods to improve the corrosion resistance of Mg and its alloys. The current progress on in vitro cytotoxicity and in vivo biocompatibility properties of these metals was also reviewed. This review aimed to provide a reference for further research and development (R&D) of biodegradable Mg and its alloys with regard to the evaluation of their corrosion process and biocompatibility and facilitation of their translation to clinical applications.