Thread-structural microneedles loaded with engineered exosomes for annulus fibrosus repair by regulating mitophagy recovery and extracellular matrix homeostasis

Autor: Shaojun Hu, Meng Zhu, Hongyuan Xing, Yucheng Xue, Jun Li, Zhan Wang, Zhou Zhu, Miaojie Fang, Zilong Li, Jianbin Xu, Yong He, Ning Zhang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Bioactive Materials, Vol 37, Iss , Pp 1-13 (2024)
Druh dokumentu: article
ISSN: 2452-199X
DOI: 10.1016/j.bioactmat.2024.03.006
Popis: Low back pain is among the most grave public health concerns worldwide and the major clinical manifestation of intervertebral disc degeneration (IVDD). The destruction of annulus fibrosus (AF) is the primary cause of IVDD. A sustainable and stable treatment system for IVDD is lacking because of the special organizational structure and low nutrient supply of AF. We here found that IVDD results in the impaired mitochondrial function of AF tissue, and mitochondrial autophagy (mitophagy) plays a protective role in this process. We therefore reported a thread-structural microneedle (T-MN) matching the ring structure of AF. Based on the adsorption effect of laminin, our T-MN could load with bone marrow mesenchymal stem cell-derived exosomes to envelope the regulating mitophagy microRNA (miRNA 378), named as T-MN@EXO@miR−378. In general, we offered in situ locking in the defect site of AF to prevent nucleus pulposus leakage and promoted AF repair. The design of the thread structure was aimed at bionically matching the layered AF structure, thereby providing stronger adhesion. The T-MN@EXO@miR−378 effectively attached to AF and slowly released therapeutic engineered exosomes, and prevented IVDD progression by restoring mitophagy, promoting AF cell proliferation and migration, and inhibiting the pathological remodeling of the extracellular matrix. This functional system can be used as an excellent tool for sustained drug release and has a certain prospect in substituting the conventional treatment of IVDD.
Databáze: Directory of Open Access Journals