Authors
Xiaorong Li, Mengsha Li, Zhenghao Li, Jiaying Gu, Linzhen Mo, Yuetong Zhu, Yang Chen, Leli Zeng, Yihang Pan, Chao Zhang, Yunhui Si
Published in
Advanced materials (Deerfield Beach, Fla.). Pages e75185. Sep 27, 2026. Epub Sep 27, 2026.
Abstract
Dysregulated bone remodeling, attenuated endogenous osteogenic capacity, and the lack of bone-targeting capability in therapeutics constitute the core challenges in current clinical interventions for osteoporosis. In this study, a hybrid nanodelivery system integrating betaine-loaded metal-organic frameworks with engineered exosomes (BZ@Exos) is constructed to restore bone metabolic homeostasis and improve bone microstructure. The engineered exosomes co-overexpressing CXCR4 and CD47 proteins on the surface exhibit high bone tissue targeting efficiency and evade clearance by the mononuclear phagocyte system, while ZIF-8 enables stable encapsulation of betaine. Internalized betaine promotes nuclear translocation of TFEB via targeted binding to the 14-3-3 protein, enhances autophagic flux in senescent bone marrow mesenchymal stem cells (BMSCs), and thereby facilitates their osteogenic differentiation. In parallel, BZ@Exos significantly inhibits osteoclast-mediated bone resorption and restores bone metabolic homeostasis. In vivo assays demonstrate that intravenously administered BZ@Exos successfully reverses bone loss and alleviates senescence-related phenotypes in ovariectomized rat models of osteoporosis. This novel therapeutic system with integrated functions of bone homeostasis remodeling, regenerative potential restoration, and precise targeting provides a new perspective for osteoporosis treatment.
PMID:
42800918
Bibliographic data and abstract were imported from PubMed on 27 Sep 2026.
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