Boosting cartilage repair with silk fibroin-DNA hydrogel-based cartilage organoid precursor

Congyi Shen; Jian Wang; Guangfeng Li; Shuyue Hao; Yan Wu; Peiran Song; Yafei Han; Mengmeng Li; Guangchao Wang; Ke Xu; Hao Zhang; Xiaoxiang Ren; Yingying Jing; Ru Yang; Zhen Geng; Jiacan Su

Bioactive Materials (May 2024)

Boosting cartilage repair with silk fibroin-DNA hydrogel-based cartilage organoid precursor

Congyi Shen,
Jian Wang,
Guangfeng Li,
Shuyue Hao,
Yan Wu,
Peiran Song,
Yafei Han,
Mengmeng Li,
Guangchao Wang,
Ke Xu,
Hao Zhang,
Xiaoxiang Ren,
Yingying Jing,
Ru Yang,
Zhen Geng,
Jiacan Su

Affiliations

Congyi Shen: Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Organoid Research Center, Shanghai University, Shanghai, 200444, China; School of Medicine, Shanghai University, Shanghai, 200444, China; School of Life Sciences, Shanghai University, Shanghai, 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
Jian Wang: Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Organoid Research Center, Shanghai University, Shanghai, 200444, China; School of Medicine, Shanghai University, Shanghai, 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China; Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
Guangfeng Li: Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Organoid Research Center, Shanghai University, Shanghai, 200444, China; School of Medicine, Shanghai University, Shanghai, 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China; Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai, 200941, China
Shuyue Hao: Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Organoid Research Center, Shanghai University, Shanghai, 200444, China; School of Medicine, Shanghai University, Shanghai, 200444, China; School of Life Sciences, Shanghai University, Shanghai, 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
Yan Wu: Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Organoid Research Center, Shanghai University, Shanghai, 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
Peiran Song: Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Organoid Research Center, Shanghai University, Shanghai, 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
Yafei Han: Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Organoid Research Center, Shanghai University, Shanghai, 200444, China; School of Medicine, Shanghai University, Shanghai, 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
Mengmeng Li: Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Organoid Research Center, Shanghai University, Shanghai, 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
Guangchao Wang: Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
Ke Xu: Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Organoid Research Center, Shanghai University, Shanghai, 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
Hao Zhang: Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Organoid Research Center, Shanghai University, Shanghai, 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
Xiaoxiang Ren: Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Organoid Research Center, Shanghai University, Shanghai, 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
Yingying Jing: Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Organoid Research Center, Shanghai University, Shanghai, 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China; Corresponding author. Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
Ru Yang: Second Affiliated Hospital of Soochow University, Departments of Rheumatology and Immunology, Soochow, 215000, China; Corresponding author. Second Affiliated Hospital of Soochow University, Departments of Rheumatology and Immunology, Soochow, 215000, China.
Zhen Geng: Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Organoid Research Center, Shanghai University, Shanghai, 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China; Corresponding author. Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
Jiacan Su: Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China; Organoid Research Center, Shanghai University, Shanghai, 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China; Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China; Corresponding authors. Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.

Journal volume & issue: Vol. 35
pp. 429 – 444

Abstract

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Osteoarthritis (OA), a common degenerative disease, is characterized by high disability and imposes substantial economic impacts on individuals and society. Current clinical treatments remain inadequate for effectively managing OA. Organoids, miniature 3D tissue structures from directed differentiation of stem or progenitor cells, mimic native organ structures and functions. They are useful for drug testing and serve as active grafts for organ repair. However, organoid construction requires extracellular matrix-like 3D scaffolds for cellular growth. Hydrogel microspheres, with tunable physical and chemical properties, show promise in cartilage tissue engineering by replicating the natural microenvironment. Building on prior work on SF-DNA dual-network hydrogels for cartilage regeneration, we developed a novel RGD-SF-DNA hydrogel microsphere (RSD-MS) via a microfluidic system by integrating photopolymerization with self-assembly techniques and then modified with Pep-RGDfKA. The RSD-MSs exhibited uniform size, porous surface, and optimal swelling and degradation properties. In vitro studies demonstrated that RSD-MSs enhanced bone marrow mesenchymal stem cells (BMSCs) proliferation, adhesion, and chondrogenic differentiation. Transcriptomic analysis showed RSD-MSs induced chondrogenesis mainly through integrin-mediated adhesion pathways and glycosaminoglycan biosynthesis. Moreover, in vivo studies showed that seeding BMSCs onto RSD-MSs to create cartilage organoid precursors (COPs) significantly enhanced cartilage regeneration. In conclusion, RSD-MS was an ideal candidate for the construction and long-term cultivation of cartilage organoids, offering an innovative strategy and material choice for cartilage regeneration and tissue engineering.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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