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An immunomodulatory polypeptide hydrogel for osteochondral defect repair.

ABSTRACT: 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.

SUBMITTER: Yang M

PROVIDER: S-EPMC9112113 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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An immunomodulatory polypeptide hydrogel for osteochondral defect repair.

Yang Meng M Zhang Zheng-Chu ZC Yuan Fu-Zhen FZ Deng Rong-Hui RH Yan Xin X Mao Feng-Biao FB Chen You-Rong YR Lu Hua H Yu Jia-Kuo JK

Bioactive materials 20220513

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(EG<sub>3</sub>Glu-<i>co</i>-Cys) and maleimide-functionalized polysarc ...[more]

PMID: 35600970

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Project description:Repairing cartilage tissue is a serious global challenge. Herein, we focus on wood skeletal structures that are highly porous for cell penetration yet have load-bearing strength, and aim to synthesize wood-derived hydrogels with the ability to regenerate cartilage tissues. The hydrogels were synthesized by wood delignification and the subsequent intercalation of citric acid (CA), which is involved in tricarboxylic acid cycles and essential for energy production, and N-acetylglucosamine (NAG), which is a cartilage glycosaminoglycan, among cellulose microfibrils. CA and NAG intercalation increased the amorphous region of the cellulose microfibrils and endowed them with flexibility while maintaining the skeletal structure of the wood. Consequently, the CA-NAG-treated wood hydrogels became twistable and bendable, and the acquired stiffness, compressive strength, water content, and cushioning characteristics were similar to those of the cartilage. In rabbit femur cartilage defects, CA-NAG-treated wood hydrogels induced the differentiation of surrounding cells into chondrocytes. Consequently, the CA-NAG-treated wood hydrogels repaired cartilage defects, whereas the collagen scaffolds, delignified wood materials, and CA-treated wood hydrogels did not. The CA-NAG-treated wood hydrogels exhibit superior structural and mechanical characteristics over conventional cellulose-fiber-containing scaffolds. Furthermore, the CA-NAG-treated wood hydrogels can effectively repair cartilage on their own, whereas conventional natural and synthetic polymeric materials need to be combined with cells and growth factors to achieve a sufficient therapeutic effect. Therefore, the CA-NAG-treated wood hydrogels successfully address the limitations of current therapies that either fail to repair articular cartilage or sacrifice healthy cartilage. To our knowledge, this is the pioneer study on the utilization of thinned wood for tissue engineering, which will contribute to solving both global health and environmental problems and to creating a sustainable society.

Dataset Information

An immunomodulatory polypeptide hydrogel for osteochondral defect repair.

Publications

An immunomodulatory polypeptide hydrogel for osteochondral defect repair.

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