Li Shihao, Sun Houyi, Lu Qunshan, Qiao Junran, Luo Yange, Chu Ziyue, Liu Dehua, Zhou Libo, Liu Peilai
Department of Orthopaedic Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China.
School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China.
Biomater Adv. 2025 Aug;173:214292. doi: 10.1016/j.bioadv.2025.214292. Epub 2025 Mar 25.
Cartilage defects play a key role in osteoarthritis, causing functional impairment as the disease progresses. Microfracture surgery is commonly used to treat articular cartilage defects, providing early pain relief and functional improvement. However, the blood clot formed during the procedure differs from the natural cartilage microenvironment, hindering hyaline cartilage formation and promoting fibrocartilage, which limits long-term outcomes. This study proposes combining a bionic flexible extracellular matrix (ECM) scaffold with microfracture surgery as a treatment for cartilage defects. By filling the microfracture site with the scaffold and thermosensitive agarose gel, we can anchor BMSCs leaking from the bone marrow while creating a 3D microenvironment that regulates stem cell differentiation. Our results show that the scaffold's mechanical strength is comparable to that of hyaline cartilage, offering excellent biomimetic properties and biocompatibility. In vitro, BMSCs migrating into the scaffold exhibited a survival rate of nearly 90 % by day 2, significantly higher than the 25 % survival rate in the control agarose gel group, with cells observed anchoring around the scaffold. In vivo, stem cells anchored to the scaffold successfully differentiated into articular hyaline cartilage, driven by the combined effects of the scaffold's physical structure and its contained cytokines. The generated hyaline cartilage maintains homeostasis over time, reducing the risk of fibrocartilage formation. This strategy addresses a key limitation of microfracture surgery, where regenerated cartilage is often fibrocartilage, offering a promising new approach for cartilage repair.
软骨缺损在骨关节炎中起关键作用，随着疾病进展会导致功能障碍。微骨折手术常用于治疗关节软骨缺损，能提供早期的疼痛缓解和功能改善。然而，手术过程中形成的血凝块与天然软骨微环境不同，阻碍透明软骨形成并促进纤维软骨生成，这限制了长期疗效。本研究提出将仿生柔性细胞外基质（ECM）支架与微骨折手术相结合来治疗软骨缺损。通过用支架和热敏性琼脂糖凝胶填充微骨折部位，我们可以锚定从骨髓中漏出的骨髓间充质干细胞（BMSCs），同时创建一个调节干细胞分化的三维微环境。我们的结果表明，该支架的机械强度与透明软骨相当，具有出色的仿生性能和生物相容性。在体外，迁移到支架中的BMSCs在第2天时存活率接近90%，显著高于对照琼脂糖凝胶组25%的存活率，且观察到细胞锚定在支架周围。在体内，锚定在支架上的干细胞在支架的物理结构及其所含细胞因子的共同作用下成功分化为关节透明软骨。生成的透明软骨随时间维持内环境稳定，降低了纤维软骨形成的风险。该策略解决了微骨折手术的一个关键局限性，即再生软骨往往是纤维软骨，为软骨修复提供了一种有前景的新方法。
