Natural Biomaterials for Osteochondral Repair: From Source to Strategy.

Abstract

Osteochondral tissue repair remains a formidable clinical challenge due to its complex layered structure and limited intrinsic healing capacity. Compared with synthetic materials, natural biomaterials offer distinct advantages, including excellent biocompatibility, intrinsic bioactivity, and structural similarity to native tissues, making them particularly well-suited for recreating the native tissue microenvironment and guiding cellular behavior. This review systematically examines natural biomaterials used in osteochondral repair according to their biological origin, covering human-derived, animal-derived, plant-derived, and microbial-derived categories, and discusses how the source-specific biological properties of each category underpin their respective repair mechanisms and applications. Within animal-derived materials, particular attention is given to decellularization strategies, as the choice of method critically determines the preservation of bioactive components and the immunogenic profile of the resulting scaffold. Notably, 91.5% of the 47 osteochondral repair products approved globally since 2000 incorporate natural materials, further underscoring their enduring clinical relevance. We further highlight that the absence of standardized preparation, quality control, and evaluation frameworks remains an important challenge for broader clinical adoption. Establishing reproducible and verifiable standards will be essential to bridging the gap between laboratory innovation and clinical translation.