Multifunctional hydrogel scaffolds for endogenous osteochondral regeneration

Abstract

Osteochondral defects, frequently resulting from trauma, infection, or degenerative joint disease, present a significant clinical challenge due to their limited intrinsic healing capacity. Conventional cell-based therapies face limitations including immune rejection, high costs, and regulatory hurdles. Endogenous tissue engineering, which harnesses the body's own repair machinery through biomaterial-mediated recruitment and differentiation of host stem cells, offers a promising alternative. Hydrogel scaffolds, owing to their extracellular matrix-mimetic architecture, tunable physicochemical properties, and capacity for bioactive factor delivery, have emerged as versatile platforms for endogenous osteochondral regeneration. This review provides a strategic overview of hydrogel-based endogenous tissue engineering, covering: (1) the biological rationale for leveraging host cell sources; (2) the design of hydrogels as extracellular matrix -mimetic niches; (3) key regulatory factors; (4) innovative material design strategies. We also discuss current challenges related to long-term functionality, scaffold integration, and clinical translation, offering insights into the development of next-generation hydrogel systems for minimally invasive and effective osteochondral regeneration.