An immunomodulatory polypeptide hydrogel for osteochondral defect repair

• DOI: 10.1016/j.bioactmat.2022.05.008
• Publication Date: 2022-05-13T00:39:59Z
• Authors: Meng Yang; Zheng-Chu Zhang; Fu-Zhen Yuan; Rong-Hui Deng; Xin Yan; Feng-Biao Mao; You-Rong Chen; Hua Lu; Jia-Kuo Yu
• Keywords: 0301 basic medicine; Foreign-body reaction; QH301-705.5; Immunoregulation; 02 engineering and technology; Osteochondral regeneration; Article; 3. Good health; Polypeptide hydrogel; 03 medical and health sciences; TA401-492; Mesenchymal stem cells; Biology (General); 0210 nano-technology; Materials of engineering and construction. Mechanics of materials

Osteochondral injury is a common and frequent orthopedic disease that can lead to more serious degenerative joint disease. Tissue engineering is a promising modality for osteochondral repair, but the implanted scaffolds are often immunogenic and can induce unwanted foreign body reaction (FBR). Here, we prepare a polypept(o)ide-based PAA-RGD hydrogel using a novel thiol/thioester dual-functionalized hyperbranched polypeptide P(EG3Glu-co-Cys) and maleimide-functionalized polysarcosine under biologically benign conditions. The PAA-RGD hydrogel shows suitable biodegradability, excellent biocompatibility, and low immunogenicity, which together lead to optimal performance for osteochondral repair in New Zealand white rabbits even at the early stage of implantation. Further in vitro and in vivo mechanistic studies corroborate the immunomodulatory role of the PAA-RGD hydrogel, which induces minimum FBR responses and a high level of polarization of macrophages into the immunosuppressive M2 subtypes. These findings demonstrate the promising potential of the PAA-RGD hydrogel for osteochondral regeneration and highlight the importance of immunomodulation. The results may inspire the development of PAA-based materials for not only osteochondral defect repair but also various other tissue engineering and bio-implantation applications.