Advancing Scaffold-Assisted Modality for In Situ Osteochondral Regeneration: A Shift From Biodegradable to Bioadaptable.

Over the decades, the management of osteochondral lesions remains a significant yet unmet medical challenge without curative solutions to date. Owing to the complex nature of osteochondral units with multi-tissues and multicellularity, and inherently divergent cellular turnover capacities, current clinical practices often fall short of robust and satisfactory repair efficacy. Alternative strategies, particularly tissue engineering assisted with biomaterial scaffolds, achieve considerable advances, with the emerging pursuit of a more cost-effective approach of in situ osteochondral regeneration, as evolving toward cell-free modalities. By leveraging endogenous cell sources and innate regenerative potential facilitated with instructive scaffolds, promising results are anticipated and being evidenced. Accordingly, a paradigm shift is occurring in scaffold development, from biodegradable and biocompatible to bioadaptable in spatiotemporal control. Hence, this review summarizes the ongoing progress in deploying bioadaptable criteria for scaffold-based engineering in endogenous osteochondral repair, with emphases on precise control over the scaffolding material, degradation, structure and biomechanics, and surface and biointerfacial characteristics, alongside their distinguished impact on the outcomes. Future outlooks of a highlight on advanced, frontier materials, technologies, and tools tailoring precision medicine and smart healthcare are provided, which potentially paves the path toward the ultimate goal of complete osteochondral regeneration with function restoration.