Biomimetically hierarchical scaffolds drive critical-sized osteochondral tissue regeneration

This study presents a pioneering approach utilizing hierarchically functionalized scaffolds to foster anisotropic osteochondral tissue regeneration, leveraging the integration of distinct yet interconnected layers. We developed 3D-printed polydopamine-modified polycaprolactone (PCL) scaffolds, which were subsequently covered with a layer of electrospun PCL-gelatin fibers, and then functionalized with gelatin-bone morphogenetic protein-2 (BMP-2) following oxygen plasma surface treatments, creating a hierarchically organized multi-phasic architecture. This interconnected porous microstructure enabled controllable degradation while maintaining mechanical integrity and hydroxyapatite mineralization. In vitro assessments demonstrated that the scaffolds provided superior support for rat bone marrow mesenchymal stem cells, marked by their enhanced adhesion, viability, and proliferation. Increased alkaline phosphatase activity and osteocalcin expression over 14 days indicated that the scaffolds enhanced osteogenic performance, likely due to BMP-2 interaction with serum proteins, as supported by simulation studies, augmenting growth factor bioavailability. In vivo investigations in rabbit critical-sized osteochondral defects at 4- and 12-week post-implantation demonstrated that the multi-phasic scaffolds notably promoted secretion of type I and II collagen, neo-tissue formation, and integration with surrounding tissue, with significant results observed at 12 weeks. These findings indicate the potential of multi-phasic scaffolds for osteochondral tissue regeneration.