Xenogeneic decellularized materials for integrated osteochondral repair

Repairing osteochondral defects remains a clinical hurdle, primarily attributed to the unique hierarchical anatomical structure of osteochondral tissue and the complex structural-functional heterogeneities of the bone-cartilage interface. Conventional strategies for osteochondral defect repair, however, suffer from inherent limitations. By retaining the native extracellular matrix (ECM), decellularized constructs can recapitulate the 3D porous architecture and compositional-mechanical gradient of osteochondral tissue. Integrated xenogeneic osteochondral decellularized scaffolds have thus emerged as a research hotspot in defect repair, owing to their superior structural biomimicry and retention of native tissue bioactivity. This review first systematically outlines current osteochondral decellularization technologies and key in vitro evaluation indices. Furthermore, it summarizes the in vivo repair efficacy of such scaffolds in preclinical animal models. Ultimately, it highlights key challenges in current research, including residual immunogenicity and mismatched degradation rates of materials, and discusses the potential applications of gene editing and dynamic mechanical stimulation. This review aims to provide insights into the technological optimization and clinical translation of integrated xenogeneic osteochondral decellularized scaffolds, thereby facilitating the clinical implementation of osteochondral defect repair strategies. • Summary of current xenogeneic osteochondral decellularization techniques. • Analysis of structure-function relationship and effect of gradient structures. • Evaluation of interface/surface strategies boosting scaffold integration/activity. • Review of existing studies to identify immunogenicity and degradation bottlenecks. • Outlook on emerging techniques for overcoming clinical translation barriers.