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Bone fractures are the most common human trauma. Fracture repair is a regeneration process, which summarizes many events of skeletal development [1]. Under healthy conditions, bones have a unique ability to recover that does not lead to the formation of scarring. But, a complex or severely damaged fracture (i.e., cracks above critical size) may not heal, resulting in a nonunion fracture [2]. Comorbidities such as diabetes [3], hereditary factors [4] and an unhealthy lifestyle [5] (e.g., alcohol abuse or smoking) are associated with a heightened risk of delayed healing and nonunion of fractures. Besides, improper treatment may lead to nonunion of fractures. The treatment strategy of bone defects is mainly directed toward autogenous bone grafts, which constitute the clinical “gold standard” for the treatment of bone defects due to their osteoconductivity and osteoinduction [6]. Although autotransplantation is restricted by the volume of bone which is obtained from the iliac crest and afterwards transplanted to the defect, it does not cause an immune response [7]. Moreover, complications also exist, such as local hematoma and bone graft reconstruction. Using the same or an xenogeneic or an allogeneic bone source is a way of overcoming the limitation of the donor site and autograft supply. Xenografts, mainly from bovine origins, have conductive/ osteoconductive ability [8]. Alternatively, allogeneic bone obtained from cadaveric sources has the advantages of being osteoinductive and osteoconductive, and can be obtained in various shapes and sizes through a regional tissue bank [9]. But studies stemming from clinical trials have identified that allograft treatments usually produce an increased risk of transmission of infectious disease, immunogenicity, and host rejection [10, 11]. In recent years, there have been increasing applications of growth factors (GFs), 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou City, Zhejiang Province 325035, China

bio integration/bio integration

Bioactive Factors-imprinted Scaffold Vehicles for Promoting Bone Healing: The Potential Strategies and the Confronted Challenges for Clinical Production