Synergetic integrations of bone marrow stem cells and transforming growth factor‐β1 loaded chitosan nanoparticles blended silk fibroin injectable hydrogel to enhance repair and regeneration potential in articular cartilage tissue
Dong Zheng, Tong Chen, Long Han, Songwei Lv, Jianjian Yin, Kaiyuan Yang, Yuji Wang, Nanwei Xu
Abstract
The cartilage repair and regeneration show inadequate self-healing capability and have some complications, which are inordinate challenges in clinical therapy. Biopolymeric injectable hydrogels, a prominent type of cell-carrier as well tissue engineering scaffolding materials, establish promising therapeutic potential of stem cell-based cartilage-regeneration treatment. In addition, injectable scaffolding biomaterial should have rapid gelation properties with adequate rheological and mechanical properties. In the present investigation, we developed and fabricated the macromolecular silk fibroin blended with polylysine modified chitosan polymer (SF/PCS) using thermal-sensitive glycerophosphate (GP), which contains effective gelation ability, morphology, porosity and also has enhanced mechanical properties to induce physical applicability, cell proliferation and nutrient exchange in the cell-based treatment. The developed and optimised injectable hydrogel group has good biocompatibility with human fibroblast (L929) cells and bone marrow-derived mesenchymal stem cells (BMSCs). Additionally, it was found that SF/PCS hydrogel group could sustainably release TGF-β1 and efficiently regulate cartilage-specific and inflammatory-related gene expressions. Finally, the cartilage-regeneration potential of the hydrogel groups embedded with and without BMSCs were evaluated in SD rat models under histopathological analysis, which showed promising cartilage repair. Overall, we conclude that the TGF-β1-SF/PCS injectable hydrogel demonstrates enhanced in vitro and in vivo tissue regeneration properties, which lead to efficacious therapeutic potential in cartilage regeneration.