Preservation of chondrocyte microspheroids by local sustained hydrogen supply improves osteoarthritic cartilage repair.
Shengqiang Chen, Mingrui Luo, Sizhen Chen, Danyang Chen, Lingting Zeng, Lina Shangguan, Zhengji Sun, Guanglin Li, Wenjiang Ding, Wei Tang, Qianjun He
Abstract
The inflammatory pathological microenvironment of osteoarthritis (OA) degrades the cell state and function of stem cell-derived grafts and presents a major obstacle to developing effective cell therapies. Here, we show that the viability and hyaline cartilage phenotype of bone marrow-derived mesenchymal stem cell (BMSC)-derived chondrocyte microspheroids (CMSs) can be efficiently preserved during spheroidization with persistent H2 supply and in an OA microenvironment. We therefore developed TiSi2 nanosheets (TSN) that hydrolytically generate a sustained (> 2 months) high dose of H2 and construct a H2-releasing hydrogel transplant (TSN/CMS-Gel) by encapsulating TSN and CMSs within a photo-crosslinking hydrogel (Gel). Transplantation of TSN/CMS-Gel achieves a strong survival of chondrocytes in a rodent OA model and promotes the rapid and efficient repair of sheep osteoarthritic critical-size cartilage defects, as well as the reversal of osteoarthritic progression within 6 months. The proposed strategy of locally sustaining H2-mediated preservation of transplanted chondrocytes in the pathological microenvironment opens new opportunities to enhance cell transplantation outcomes.