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 osteochondral defects (OCD) remains a great challenge in orthopaedics. Tissue engineering holds a good promise for regeneration of OCD. In the light of tissue engineering, it is critical to establish an appropriate animal model to evaluate the degradability, biocompatibility, and interaction of implanted biomaterials with host bone/cartilage tissues for OCD repair in vivo. Currently, model animals that are commonly deployed to create osteochondral lesions range from rats, rabbits, dogs, pigs, goats, and sheep horses to nonhuman primates. It is essential to understand the advantages and disadvantages of each animal model in terms of the accuracy and effectiveness of the experiment. Therefore, this review aims to introduce the common animal models of OCD for testing biomaterials and to discuss their applications in translational research. In addition, we have reviewed surgical protocols for establishing OCD models and biomaterials that promote osteochondral regeneration. For small animals, the non-load-bearing region such as the groove of femoral condyle is commonly chosen for testing degradation, biocompatibility, and interaction of implanted biomaterials with host tissues. For large animals, closer to clinical application, the load-bearing region (medial femoral condyle) is chosen for testing the durability and healing outcome of biomaterials. This review provides an important reference for selecting a suitable animal model for the development of new strategies for osteochondral regeneration.

Size and location of the lesion, subchondral collapse occurrence, and articular cartilage involvement are general disease progression criteria for direct osteonecrosis of the femoral head (ONFH) classifications. Treatment options for ONFH are usually based on individual factors and lesion characteristics. Although spontaneous repair of ONFH occurs in some cases, untreated ONFH is unlikely to escape the fate of subchondral collapse and usually ends up with total hip arthroplasty. Operations to preserve the femoral head, e.g., core decompression and bone grafting, are usually recommended in younger patients. They are helpful to relieve pain and improve function in the affected femoral head without subchondral collapse, however, poor prognosis after surgical procedures remains the major problem for ONFH. Pharmacological and physical therapies only work in the early stage of ONFH and have also been recommended as a supplement or prevention treatment for osteonecrosis. Following advances in basic science, many new insights focus on bone tissue engineering to optimize therapies and facilitate prognosis of ONFH. In this review, disease classifications, current treatment options, potential therapies, and the relevant translational barriers are reviewed in the context of clinical application and preclinical exploration, which would provide guidance for preferable treatment options and translation into novel therapies.