Functionalized cell-free scaffolds for bone defect repair inspired by self-healing of bone fractures: A review and new perspectives

Studies have demonstrated that scaffolds, a component of bone tissue engineering, play an indispensable role in bone repair. However, these scaffolds involving ex-vivo cultivated cells seeded have disadvantages in clinical practice, such as limited autologous cells, time-consuming cell expansion procedures, low survival rate and immune-rejection issues. To overcome these disadvantages, recent focus has been placed on the design of functionalized cell-free scaffolds, instead of cell-seeded scaffolds, that can reduplicate the natural self-healing events of bone fractures, such as inflammation, cell recruitment, vascularization, and osteogenic differentiation. New approaches and applications in tissue engineering and regenerative medicine continue to drive the development of functionalized cell-free scaffolds for bone repair. In this review, the self-healing processes were highlighted, and approaches for the functionalization were summarized. Also, ongoing efforts and breakthroughs in the field of functionalization for bone defect repair were discussed. Finally, a brief summery and new perspectives for functionalization strategies were presented to provide guidelines for further efforts in the design of bioinspired cell-free scaffolds.