Synergizing adaptive immunity and regenerative signals to enhance osteochondral defects repair

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials Pub Date : 2024-12-21 DOI:10.1016/j.bioactmat.2024.12.011

Changjian Lin , Chenting Ying , Yibo Xu , Yuxuan Zou , Ruihan Chen , Kaicheng Xu , Xiaoxiao Ji , Qihua Cao , Jiahui Weng , Lifeng Jiang , Chenyi Ye , Kai Xu , Yuzhe He , Weijun Li , Lidong Wu , Jisheng Ran , Yan Xiong , Xiaohua Yu , Jiapeng Bao

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Abstract

In clinical practice, repairing osteochondral defects (OCDs) is challenging because of the complex cartilage/subchondral bone structure and intricate immunological microenvironment. Here, we identify the crucial role of adaptive immunity dysfunction by revealing that an increase of T helper 17 (Th17) cells exacerbated osteochondral tissue degradation via its pro-inflammatory cytokine interleukin-17 (IL-17) in the early-stage OCDs. Next, we leveraged this adaptive immunity mechanism and combined it with regenerative signals to develop a multifunctional hydrogel system capable of simultaneously tackling immune dysfunction and regenerative deficiency. Rapid IL-4 release from the methacrylated hyaluronic acid (HAMA) hydrogel exerts a potent immunomodulatory effect by inhibiting the differentiation and function of Th17 cells. Moreover, transforming growth factor-beta1 anchored on methacrylated hyaluronic acid and heparin (HAMA@HepMA) microparticles provides sustained regenerative signals, which synergistically transform the pro-inflammatory microenvironment into a pro-regenerative niche for enhanced OCDs healing. Our study suggests that targeting specific immune pathways can significantly enhance the efficacy of regenerative strategies, paving the way for innovative treatments in orthopedic medicine.

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来源期刊

Bioactive Materials Biochemistry, Genetics and Molecular Biology-Biotechnology

CiteScore

28.00

自引率

6.30%

发文量

436

审稿时长

20 days

期刊介绍： Bioactive Materials is a peer-reviewed research publication that focuses on advancements in bioactive materials. The journal accepts research papers, reviews, and rapid communications in the field of next-generation biomaterials that interact with cells, tissues, and organs in various living organisms. The primary goal of Bioactive Materials is to promote the science and engineering of biomaterials that exhibit adaptiveness to the biological environment. These materials are specifically designed to stimulate or direct appropriate cell and tissue responses or regulate interactions with microorganisms. The journal covers a wide range of bioactive materials, including those that are engineered or designed in terms of their physical form (e.g. particulate, fiber), topology (e.g. porosity, surface roughness), or dimensions (ranging from macro to nano-scales). Contributions are sought from the following categories of bioactive materials: Bioactive metals and alloys Bioactive inorganics: ceramics, glasses, and carbon-based materials Bioactive polymers and gels Bioactive materials derived from natural sources Bioactive composites These materials find applications in human and veterinary medicine, such as implants, tissue engineering scaffolds, cell/drug/gene carriers, as well as imaging and sensing devices.