“…Bone defects associated with trauma, infection, and tumor are common clinical symptoms in orthopedics, which require frequent surgical intervention. In most treatments, bone substitutes, including autologous, allogeneic, and artificial bones, are usually required. , Although autologous and allogeneic bone grafts possess superior osteoconduction and osteoinduction, the risks of immune rejection, disease transmission, donor site complications, and limited supply hinder their clinical application. , Bone tissue engineering is a prospective approach to induce bone regeneration and repair. However, the introduction of supraphysiological exogenous growth factors, such as bone morphogenic protein-2 (BMP-2), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF), may cause adverse effects like ectopic bone formation, vascular leakage, osteoclast activation, and osteolysis. − …”