可注射的颗粒状细胞外基质(gECM)水凝胶移植物可促进大型动物模型中关节软骨的整合性修复
简介
本研究在羊股骨髁临界尺寸软骨缺损模型中评估了一种由脱细胞软骨微粒构建的可注射颗粒状细胞外基质(gECM)水凝胶。术后12个月,gECM修复组织的摩擦学和压缩力学性能接近天然软骨,富含II型胶原、蛋白聚糖/胶原比优良且I型胶原极少,MRI指标改善并可见侧方整合及软骨下骨重塑。该材料优于微钻孔对照,为关节软骨整合修复提供了有前景的转化方向。
英文摘要
UNLABELLED: Focal injuries to articular cartilage in load-bearing joints fail to heal and often progress to degeneration, underscoring the need for repair strategies that result in restored cartilage structure and function rather than fibrocartilage formation. Granular extracellular matrix (gECM) hydrogels, flowable grafts composed of densely-packed matrix particles, offer a promising approach but lack long-term functional validation in large-animal models. Here, we developed a flowable gECM hydrogel composed of decellularized cartilage microparticles incorporated within a thiol-functionalized hyaluronan matrix. Proteomic analysis confirmed enrichment of cartilage-specific gECM matrisome components. When implanted into critical-sized femoral condyle defects in a goat model and evaluated 12 months post-implantation, both gECM hydrogel and microdrilling (surgical controls) achieved >80% defect filling. However, in contrast to microdrilling, gECM repair tissue exhibited surface tribological (friction, adhesion) and compressive mechanical properties comparable to native cartilage, with a similar proteoglycan-to-collagen ratio, enrichment of type II collagen, minimal type I collagen (typical of a fibrous scar), improved quantitative MRI metrics, and evidence of lateral cartilage integration and subchondral bone remodeling. Together, these findings demonstrate that a flowable gECM hydrogel supports integrative, cartilage-like repair in a load-bearing joint, supporting advancement of this approach toward clinical translation. ONE SENTENCE SUMMARY: A granular ECM hydrogel implanted in a goat condyle provided a robust repair, filling the defect tissue with integrated, hyaline-like cartilage at 12 months.