Articular cartilage tissue has limited self-repair capabilities, with damage frequently progressing to irreversible degeneration. Engineered tissues constructed through bioprinting and embedded with stem cell aggregates offer promising therapeutic alternatives. Aggregates of bone marrow mesenchymal stromal cells (BMSCs) demonstrate enhanced and more rapid chondrogenic differentiation than isolated cells, thus facilitating cartilage repair. However, it remains a key challenge to precisely control biochemical microenvironments to regulate cellular adhesion and cohesion within bioprinted matrices simultaneously. Herein, this work reports a bioprintable hydrogel matrix with high cellular adhesion and aggregation properties for cartilage repair. The hydrogel comprises an enhanced cell-adhesive gelatin methacrylate and a cell-cohesive chitosan methacrylate (CHMA), both of which are subjected to photo-initiated crosslinking. By precisely adjusting the CHMA content, the mechanical stability and biochemical cues of the hydrogels are finely tuned to promote cellular aggregation, chondrogenic differentiation and cartilage repair implantation. Multi-layer constructs encapsulated with BMSCs, with high cell viability reaching 91.1%, are bioprinted and photo-crosslinked to support chondrogenic differentiation for 21 days. BMSCs rapidly form aggregates and display efficient chondrogenic differentiation both on the hydrogels and within bioprinted constructs, as evidenced by the upregulated expression of Sox9, Aggrecan and Collagen 2a1 genes, along with high protein levels. Transplantation of these BMSC-laden bioprinted hydrogels into cartilaginous defects demonstrates effective hyaline cartilage repair. Overall, this cell-responsive hydrogel scaffold holds immense promise for applications in cartilage tissue engineering.

中文翻译：

---

生物打印仿生水凝胶基质引导干细胞聚集以增强软骨形成和软骨再生

关节软骨组织的自我修复能力有限，损伤经常发展为不可逆的退化。通过生物打印构建并嵌入干细胞聚集体的工程组织提供了有前途的治疗替代方案。骨髓间充质基质细胞 (BMSC) 的聚集体表现出比分离的细胞更强且更快速的软骨形成分化，从而促进软骨修复。然而，精确控制生化微环境以同时调节生物打印基质内的细胞粘附和内聚力仍然是一个关键挑战。在此，这项工作报告了一种可生物打印的水凝胶基质，具有高细胞粘附和聚集特性，可用于软骨修复。该水凝胶包含增强的细胞粘附性明胶甲基丙烯酸酯和细胞粘附性壳聚糖甲基丙烯酸酯（CHMA），两者均经过光引发交联。通过精确调节 CHMA 含量，对水凝胶的机械稳定性和生化信号进行微调，以促进细胞聚集、软骨分化和软骨修复植入。封装有 BMSC 的多层结构，细胞活力高达 91.1%，经过生物打印和光交联，可支持软骨分化 21 天。 Sox9、Aggrecan 和 Collagen 2a1 基因的表达上调以及高蛋白水平证明了 BMSC 快速形成聚集体并在水凝胶上和生物打印构建体中显示出有效的软骨形成分化。将这些载有 BMSC 的生物打印水凝胶移植到软骨缺损中，可以有效修复透明软骨。总体而言，这种细胞响应性水凝胶支架在软骨组织工程中的应用具有巨大的前景。