Osteochondral regenerative engineering: challenges, state-of-the-art and translational perspectives

Abstract

Despite quantum leaps, the biomimetic regeneration of cartilage and osteochondral regeneration remain a major challenge, owing to the complex and hierarchical nature of compositional, structural and functional properties. In this review, an account of the prevailing challenges in biomimicking the gradients in porous microstructure, cells and ECM orientation is presented. Further, the spatial arrangement of the cues in inducing vascularization in the subchondral bone region while maintaining the avascular nature of the adjacent cartilage layer is highlighted. With rapid advancement in biomaterials science, biofabrication tools and strategies, the state-of-the-art in osteochondral regeneration since the last decade has expansively elaborated. This includes conventional and additive manufacturing of synthetic/natural/ECM-based biomaterials, tissue-specific/mesenchymal/progenitor cells, growth factors and/or signaling biomolecules. Beyond the laboratory-based research and development, the underlying challenges in translational research are also provided in a dedicated section. A new generation of biomaterial-based acellular scaffold systems with uncompromised biocompatibility and osteochondral regenerative capability is necessary to bridge the clinical demand and commercial supply. Encompassing the basic elements of osteochondral research, this review is believed to serve as a standalone guide for early career researchers, in expanding the research horizon to improve the quality of life of osteoarthritic patients affordably.

Repair of full-thickness articular cartilage defects with a 3DP-anchored three-phase complex

“…The three-phase scaffold [ 19 ] can simultaneously reconstruct full layer cartilage to repair bone and cartilage injury [ 20 ]. Levingstone et al [ 21 ] constructed a new three-phase composite scaffold in which the bone layer is made of type I collagen and hydroxyapatite, the middle was used type I and II, and cartilage is type I, II and hyaluronic acid.…”

Osteochondral organoids: current advances, applications, and upcoming challenges

“…There has been a growing focus on iPSCs due to the limitations associated with MSCs in terms of their regenerative capabilities [ 81 ]. MSCs have been used in some clinical bone regeneration.…”

Enhanced hyaline cartilage formation and continuous osteochondral regeneration via 3D-Printed heterogeneous hydrogel with multi-crosslinking inks

“…Second, the frequently overlooked aspect of rebuilding the calcification layer leads to tissue disjunction between the regenerated cartilage and subchondral bone, posing a significant obstacle to overall regenerative capacity [ 4 , 5 ]. Third, replicating the intricate gradient structure of natural osteochondral tissue using conventional fabrication techniques is challenging [ 6 ]. Therefore, attention and resolution of these disadvantages are essential for osteochondral regeneration.…”