Microfracture surgery remains the most popular treatment for articular cartilage lesions in the clinic, but often leads to the formation of inferior fibrocartilage tissue and damage to subchondral bone. To overcome these problems, extracellular matrix (ECM) scaffolds derived from decellularized natural cartilaginous tissues were introduced and showed excellent biological properties to direct the differentiation of bone marrow stem cells. However, besides the limited allogenic/allogenic supply and the risk of disease transfer from xenogeneic tissues, the effectiveness of ECM scaffolds always varied with a high variability of natural tissue quality. In this study, we developed composite scaffolds functionalized with a cell-derived ECM source, namely, bionic cartilage acellular matrix microspheres (BCAMMs), that support the chondrogenic differentiation of bone marrow cells released from microfracture. The scaffolds with BCAMMs at different developmental stages were investigated in articular cartilage regeneration and subchondral bone repair. Compared to microfracture, the addition of cell-free BCAMM scaffolds has demonstrated a great improvement of regenerated cartilage tissue quality in a rabbit model as characterized by a semi-quantitative analysis of cells, histology and biochemical assays as well as micro-CT images. Moreover, the variation in ECM properties was found to significantly affect the cartilage regeneration, highlighting the challenges of homogenous scaffolds in working with microfracture. Together, our results demonstrate that the biofunctionalized BCAMM scaffold with cell-derived ECM shows great potential to combine with microfracture for clinical translation to repair cartilage defects.

中文翻译：

---

用仿生软骨脱细胞基质微球功能化的无细胞支架，以增强对关节软骨缺损的微骨折治疗

微骨折手术仍然是临床上最常见的关节软骨损伤治疗方法，但通常会导致下软骨组织的形成和软骨下骨的损坏。为了克服这些问题，引入了从脱细胞的天然软骨组织衍生的细胞外基质（ECM）支架，它们具有出色的生物学特性，可指导骨髓干细胞的分化。然而，除了有限的同种异体/同种异体供应和从异种组织转移疾病的风险外，ECM支架的有效性总是随自然组织质量的高度变化而变化。在这项研究中，我们开发了由细胞衍生的ECM来源（即仿生软骨无细胞基质微球（BCAMM））功能化的复合支架，支持从微骨折释放的骨髓细胞的软骨分化。在关节软骨再生和软骨下骨修复中研究了处于不同发育阶段的具有BCAMM的支架。与微骨折相比，无细胞BCAMM支架的添加已证明了兔模型中再生软骨组织质量的显着改善，其特征在于细胞的半定量分析，组织学和生化分析以及微CT图像。此外，发现ECM特性的变化显着影响软骨再生，突显了均质支架在微骨折治疗中所面临的挑战。一起，