Coupling Mitochondrial Homeostasis to Oxi‐Inflamm‐Aging Network Disruption via Peptide‐Functionalized Nanocomposite Hydrogel for Osteoarthritis Intervention

软骨细胞 骨关节炎 纳米复合材料 材料科学 自愈水凝胶 壳聚糖 细胞生物学 串扰 纳米技术 生物物理学 软骨 活性氧 线粒体 化学 组织工程 癌症研究 双功能 结合 联轴节(管道) 电穿孔 医学 纳米囊 药理学
作者
Zhao Zhang,Xiaohe Wang,Pengyu Fan,Debin Cheng,Jingyi Dang,Xin Dan,Yuqiong Xia,Hongbin Fan
出处
期刊:Advanced Materials [Wiley]
卷期号:38 (24): e11804-e11804 被引量:5
标识
DOI:10.1002/adma.202511804
摘要

Osteoarthritis(OA) is an age-related degenerative joint disease, and the absence of clinically effective therapy places a substantial burden on global health. The crosstalk among oxidation, inflammation, and aging (oxi-inflamm-aging) disrupts chondrocytes homeostasis, serving as a critical driver in OA initiation and progression. Here, we developed a mitochondria-centered therapeutic strategy aimed at concomitantly disrupting the pathogenic oxi-inflamm-aging network. This strategy emphasized a novel chimeric peptide (MW) designed by integrating the mitochondrial protective MOTS-s and cartilage-targeting WYRGRL. To enhance therapeutic delivery and efficacy, the bifunctional chimeric peptide MW is immobilized onto GeSe nanosheets, which are then embedded within a multifunctional responsive hydrogel composed of HA-MAL, MMP13-sensitive peptide, and PF127 (HMP), forming the peptide-functionalized nanocomposite hydrogel (MW@GeSe@HMP). This engineered nanocomposite hydrogel not only exhibited efficient enzyme-mimicking mimetic properties to scavenge harmful oxygen radicals, but also enabled MMP-responsive targeted release in chondrocytes. Subsequent biological experiments revealed that MW@GeSe@HMP effectively disrupted the oxi-inflamm-aging network by modulating mitochondrial function, thereby maintaining chondrocyte homeostasis. Mechanistically, MW@GeSe@HMP protected chondrocytes via hindering cGAS/STING signaling. The nanocomposite hydrogel also significantly suppressed cartilage damage and matrix degradation, effectively alleviating OA progression in a rat OA model. In conclusion, this study developed a nanocomposite hydrogel integrating bioactive peptides and two-dimensional nanoenzyme, providing a prospective therapeutic strategy and potential target for OA treatment by regulating oxi-inflamm-aging integrative network.
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