Emerging Strategies for Bioactive Agent-Loaded Xenogeneic Bone Scaffolds in Regenerative Medicine: A Comprehensive Review.

The escalating global burden of an aging population and the rising incidence of secondary traumatic injuries have precipitated a mounting worldwide demand for bone grafts. However, autologous bone transplantation-the prevailing clinical "gold standard"-remains insufficient to meet this growing clinical need. Notably, rapid advancements in bone tissue engineering (BTE) have yielded diverse bone graft substitutes designed to recapitulate the three essential characteristics of bone tissue: osteoconductivity, osteoinductivity, and osteogenic potential. Within this domain, core scaffolds functioning as carriers for bioactive agents represent a highly promising strategy for treating bone defects. This review focuses on the design and fabrication of optimal xenogeneic bone scaffolds. It systematically examines commonly loaded bioactive components, including bone morphogenetic proteins (BMPs), platelet-rich plasma (PRP), natural products, active ingredients derived from traditional Chinese medicine ingredients (TCMs), and exosomes. The advantages and limitations inherent to these agents are critically analyzed. Furthermore, the review addresses current challenges and explores future research directions in bone scaffold engineering. By advancing multimodal strategies for modulating the delivery of bioactive agents, we aim to provide more effective therapeutic solutions for patients with critical bone defects.