Biphasic scaffolds produced by melt electrowriting and fused filament fabrication for osteochondral defect repair.

Repairing osteochondral defects remains a significant clinical challenge due to the distinct requirements for regenerating both articular cartilage and the underlying subchondral bone. The goal of this study was to evaluate a multi-phase scaffold that combined melt electrowriting (MEW) and fused filament fabrication (FFF) to direct simultaneous subchondral bone and articular cartilage regeneration. To determine the optimal architecture for the chondral phase of the scaffold, an in vitro study first assessed chondrogenesis of MSCs within MEW polycaprolactone scaffolds with a range of pore sizes. All pore sizes supported cartilage-specific extracellular matrix deposition without significant differences in overall matrix accumulation. Subsequently, a hybrid scaffold was fabricated, comprising a supportive FFF shell and a bi-zonal MEW insert featuring a 600 µm pore architecture. The osseous region of the scaffold was selectively functionalized with an osteoconductive nano-needle hydroxyapatite (nnHA) coating. These constructs were implanted into critically sized caprine osteochondral defects and evaluated after six months in vivo. Histological analysis revealed that the hybrid MEW-FFF scaffolds promoted significantly more new subchondral bone formation compared to empty controls (40.2% ± 12.9% vs. 22.2% ± 13.1%). Furthermore, the hybrid scaffold supported more continuous bone regeneration throughout the defect depth, with immunohistochemical staining for collagen type II and X suggesting endochondral bone formation. Despite the enhanced subchondral bone healing, the scaffold did not significantly improve the quality of hyaline cartilage repair within the chondral region of the defect. These findings demonstrate the potential of nnHA-coated MEW-FFF hybrid scaffolds to stimulate robust subchondral bone regeneration in osteochondral defects, while underscoring the significant challenge of achieving simultaneous high-quality regeneration of both bone and articular cartilage.