Emerging functionalized artificial periostea: Diverse origins, multifaceted roles and therapeutic frontiers.

Abstract

The periosteum, a specialized connective tissue layer enveloping bone surfaces, serves as a critical regulator of bone healing through its integrated neurovascular architecture, stem cell niche properties, and mechanical barrier function. Clinically, traumatic injuries or pathological conditions frequently result in periosteal tearing, avulsion, or complete loss, fundamentally disrupting its biological integrity. In practice, repairing a torn or absent periosteum is difficult, because existing options rarely recreate its coordinated biological cues and protective function. The limited availability of viable autologous periosteal grafts has propelled the engineering of artificial periosteum (AP) - bioinspired constructs designed to replicate native tissue hierarchy and functional complexity for optimized osseous regeneration. Contemporary breakthroughs in multifunctional AP have substantially elevated their therapeutic relevance, demonstrating efficacy in resolving intricate bone repair challenges. This review systematically examines biomaterial fabrication approaches for AP. It is framed around three core mechanisms that define AP function: blocking external threats, rebalancing endogenous physiology, and enabling the hierarchical coupling of osteogenesis with angiogenesis and neurogenesis. Furthermore, we evaluate emerging functionalization strategies that enhance this therapeutic precision and critically analyze the practical challenges hindering clinical translation.