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淋巴细胞衍生的工程化凋亡小体,具有炎症调节和软骨亲和性,用于骨关节炎治疗。

Lymphocyte-Derived Engineered Apoptotic Bodies with Inflammation Regulation and Cartilage Affinity for Osteoarthritis Therapy.

机构信息

Department of Biomedical Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.

NMPA Research Base of Regulatory Science for Medical Devices, Institute of Regulatory Science for Medical Devices, Huazhong University of Science and Technology, Wuhan 430074, China.

出版信息

ACS Nano. 2024 Oct 29;18(43):30084-30098. doi: 10.1021/acsnano.4c11622. Epub 2024 Oct 15.

Abstract

Apoptotic bodies as plentiful extracellular vesicles generated from apoptotic cells play a central role in signal transduction and homeostasis regulation and simultaneously switch death to regeneration to a certain extent. Herein, we designed engineered apoptotic bodies derived from T cells to have the capacity of inflammation regulation and cartilage affinity. The engineered apoptotic bodies as a natural anti-inflammation factor were encapsulated into lubricating hydrogel microspheres to achieve an injectable microsphere complex for the treatment of osteoarthritis (OA). In the above therapeutic system, the engineered apoptotic bodies acted as a biochemical cue to regulate the inflammatory microenvironment and promote chondrocyte cartilage homeostasis, whereas the lubricating hydrogel microspheres served as a biophysical stimulation to effectively reduce the friction of the cartilage surface, restore the cartilage stress, and control the slow delivery of the encapsulated engineered apoptotic bodies by friction degradation. Consequently, the current work creates an injectable and multifunctional therapeutic microsphere to advance cartilage remodeling and OA therapy.

摘要

凋亡小体作为凋亡细胞产生的大量细胞外囊泡,在信号转导和内稳态调节中发挥核心作用,同时在一定程度上使死亡向再生转变。在此,我们设计了源自 T 细胞的工程化凋亡小体,使其具有调节炎症和软骨亲和性的能力。将工程化凋亡小体作为一种天然抗炎因子包封在润滑水凝胶微球中,以实现用于治疗骨关节炎 (OA) 的可注射微球复合物。在上述治疗系统中,工程化凋亡小体作为一种生化信号调节炎症微环境并促进软骨细胞软骨内稳态,而润滑水凝胶微球作为一种生物物理刺激,有效降低软骨表面的摩擦,恢复软骨的应力,并通过摩擦降解控制包封的工程化凋亡小体的缓慢释放。因此,本工作构建了一种可注射的多功能治疗性微球,以推进软骨重塑和 OA 治疗。

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