Mimicking the native bone regenerative microenvironment for in situ repair of large physiological and pathological bone defects

Abstract

• Instead of simply using scaffolds or following the tradition principle of large bone defects treatment, we proposed a novel concept: bone regenerative microenvironment (BRM). Through the regulation of three key entities of microenvironment: physical cues, chemical cues and biological cues, a favourable BRM can be achieved and thereby repair large bone defects. • This review not only concludes the scaffolds concerning the regulation of physical, chemical and biological cues in large physiological bone defects, but proposes the requirements of scaffolds when applied in large pathological bone defects. • In addition, for future study, we also put forward several perspectives, especially the study of high adhesive hydrogel, which warrant further development. Bone is a complex biological tissue with a complicated hierarchical nanocomposite structure. The native microenvironment of the bone tissue may be significantly disrupted by large physiological and pathological bone defects. Bone defects are often treated via complex surgical procedures that involve the application of autografts or allografts. While these grafting procedures often suffer from insufficient natural bone stock and immunorejection. Moreover, these traditional treatment methods fail to simulate a regenerative microenvironment, which plays a significant role in regeneration of bone tissue and repair of large bone defects. To this end, various biomimetic scaffolds have been devised to mimic the native microenvironment of bone and thereby to simultaneously repair bone defects and promote bone regeneration. We propose here a novel concept, in vivo bone regenerative microenvironment (BRM), which enables repair of large bone defects and enhances new bone tissue formation with external regulation. In this review, we mainly focus on materials and methods for fabrication of biomimetic scaffolds, as well as their therapeutic efficacy in modulating the BRM of large physiological and pathological bone defects .