Enhanced osteogenic and angiogenic capabilities of adipose-derived stem cells in fish collagen scaffolds for treatment of femoral head osteonecrosis.

Osteonecrosis of the femoral head (ONFH) is a debilitating condition that often leads to femoral head collapse due to insufficient blood supply and impaired bone regeneration. However, effective treatment options for this condition are limited. This study explored a novel fish collagen (FC) scaffold combined with adipose-derived stem cells (ADSCs) to enhance osteogenesis and angiogenesis in ONFH. ADSCs were isolated and cultured on FC scaffolds to evaluate their biocompatibility and differentiation capacity. Osteogenic and angiogenic differentiation potentials were assessed in vitro, and the FC/ADSC combination was further evaluated in vivo using a rat model of ONFH. The molecular mechanisms were investigated via gene expression profiling and Hippo signaling pathway analysis. The FC scaffolds promoted ADSCs adhesion, proliferation, and migration without cytotoxicity. In vitro, FC/ADSCs significantly enhanced mineralization and capillary-like structure formation compared to the controls. FC/ADSCs improved bone regeneration and neovascularization in the femoral head in vivo, as confirmed by histological and immunohistochemical analyses. Mechanistically, the Hippo pathway is activated, increasing HIF-1α expression, which enhances osteogenic and angiogenic differentiation. FC scaffolds combined with ADSCs provide a promising therapeutic strategy for ONFH by facilitating bone regeneration and vascularization through the p-YAP/HIF-1α/VEGF axis. This scaffold-cell approach represents a potential advancement in ONFH treatment.