Zheng Pinxuan, Jia Qi, Li Zhongzhe, Jiang Heng Bo, Zhou Lu
Department of Stomatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department and Research Institute of Dental Biomaterials and Bioengineering, Yonsei University College of Dentistry, Seoul, Republic of Korea.
Sci Rep. 2025 May 26;15(1):18300. doi: 10.1038/s41598-025-03015-6.
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.
股骨头坏死（ONFH）是一种使人衰弱的病症，常因血液供应不足和骨再生受损而导致股骨头塌陷。然而，针对这种病症的有效治疗选择有限。本研究探索了一种新型鱼胶原蛋白（FC）支架与脂肪来源干细胞（ADSCs）相结合，以增强ONFH中的成骨作用和血管生成。分离ADSCs并在FC支架上培养，以评估其生物相容性和分化能力。在体外评估成骨和血管生成分化潜能，并使用ONFH大鼠模型在体内进一步评估FC/ADSC组合。通过基因表达谱分析和Hippo信号通路分析研究分子机制。FC支架促进ADSCs黏附、增殖和迁移，且无细胞毒性。在体外，与对照组相比，FC/ADSCs显著增强矿化和类毛细血管结构形成。组织学和免疫组织化学分析证实，FC/ADSCs在体内改善了股骨头的骨再生和新生血管形成。从机制上讲，Hippo通路被激活，增加HIF-1α表达，从而增强成骨和血管生成分化。FC支架与ADSCs相结合，通过p-YAP/HIF-1α/VEGF轴促进骨再生和血管化，为ONFH提供了一种有前景的治疗策略。这种支架-细胞方法代表了ONFH治疗的潜在进展。
