HAMA microneedles patch loaded with muscle-targeting engineered apoptotic vesicles and attenuating sarcopenia by regulating mitochondrial homeostasis.
8 affiliations
- 1Department of Orthopedics, Fuzhou University Affiliated Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
- 2Fujian Provincial Scoliosis Diagnosis and Treatment Center, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China.
- 3Clinical Medical Research Center of Provincial Hospital Affiliated to Fuzhou University, Fuzhou, China.
- 4Department of Orthopedics, Fuzhou University Affiliated Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China. [email protected].
- 5Fujian Provincial Scoliosis Diagnosis and Treatment Center, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China. [email protected].
- 6Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. [email protected].
- 7Department of Orthopedics, Fuzhou University Affiliated Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China. [email protected].
- 8Fujian Provincial Scoliosis Diagnosis and Treatment Center, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China. [email protected].
Abstract
Background
Sarcopenia is an age-related disorder characterized by the progressive loss of skeletal muscle mass and function, primarily driven by mitochondrial dysfunction, oxidative stress, and impaired satellite cell activity. Conventional therapeutic strategies have shown limited efficacy in restoring muscle performance. Apoptotic vesicles (ApoVs) derived from mesenchymal stem cells (MSCs) have recently emerged as promising therapeutic agents capable of delivering bioactive cargos to regulate cellular metabolism and attenuate tissue aging. However, the targeted delivery and functional stability of ApoVs remain major challenges.Results
We engineered human umbilical cord MSC-derived ApoVs with the muscle-specific aptamer A01B and encapsulated them in a methacrylated hyaluronic acid (HAMA) hydrogel microneedle patch to enhance tissue targeting and enable sustained release. In vitro, ApoVs were efficiently internalized by C2C12 myotubes and alleviated dexamethasone-induced atrophy by promoting proliferation, reducing oxidative stress, restoring mitochondrial structure and function, and modulating the PTEN-PI3K-AKT signaling pathway. miRNA profiling identified miR-21-5p as a key ApoV-delivered effector that activates this pathway. In vivo, treatment with the aptamer-functionalized ApoV microneedle system significantly improved muscle mass, myofiber cross-sectional area, mitochondrial oxidative capacity, and functional endurance in sarcopenic mice compared with controls.Conclusions
Our findings demonstrate that the muscle-targeted delivery of engineered ApoVs via HAMA microneedles effectively reverses key hallmarks of sarcopenia by restoring mitochondrial homeostasis and activating PI3K/AKT signaling through miR-21-5p. This microneedle-based ApoV platform provides a promising cell-free therapeutic strategy for ameliorating muscle atrophy and functional decline.
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BibTeX
@article{zhang2026hama,
title = {{HAMA microneedles patch loaded with muscle-targeting engineered apoptotic vesicles and attenuating sarcopenia by regulating mitochondrial homeostasis.}},
author = {Jiayao Zhang and Zhao Lin and Haiqi Ding and Mingjuan Zhang and Yibin Su and Linhai Yang and Dingqiang Chen and Xuanhao Chen and Jun Luo and Fuli Wen and Guoyu Yu and Zineng Yan and Jie Xu},
journal = {Journal of nanobiotechnology},
year = {2026},
month = jul,
doi = {10.1186/s12951-026-04813-4},
url = {https://europepmc.org/article/MED/42902378},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - HAMA microneedles patch loaded with muscle-targeting engineered apoptotic vesicles and attenuating sarcopenia by regulating mitochondrial homeostasis.
AU - Jiayao Zhang
AU - Zhao Lin
AU - Haiqi Ding
AU - Mingjuan Zhang
AU - Yibin Su
AU - Linhai Yang
AU - Dingqiang Chen
AU - Xuanhao Chen
AU - Jun Luo
AU - Fuli Wen
AU - Guoyu Yu
AU - Zineng Yan
AU - Jie Xu
PY - 2026
DA - 2026/07/01
JO - Journal of nanobiotechnology
DO - 10.1186/s12951-026-04813-4
UR - https://europepmc.org/article/MED/42902378
AB - Background Sarcopenia is an age-related disorder characterized by the progressive loss of skeletal muscle mass and function, primarily driven by mitochondrial dysfunction, oxidative stress, and impaired satellite cell activity. Conventional therapeutic strategies have shown limited efficacy in restoring muscle performance. Apoptotic vesicles (ApoVs) derived from mesenchymal stem cells (MSCs) have recently emerged as promising therapeutic agents capable of delivering bioactive cargos to regulate cellular metabolism and attenuate tissue aging. However, the targeted delivery and functional stability of ApoVs remain major challenges.Results We engineered human umbilical cord MSC-derived ApoVs with the muscle-specific aptamer A01B and encapsulated them in a methacrylated hyaluronic acid (HAMA) hydrogel microneedle patch to enhance tissue targeting and enable sustained release. In vitro, ApoVs were efficiently internalized by C2C12 myotubes and alleviated dexamethasone-induced atrophy by promoting proliferation, reducing oxidative stress, restoring mitochondrial structure and function, and modulating the PTEN-PI3K-AKT signaling pathway. miRNA profiling identified miR-21-5p as a key ApoV-delivered effector that activates this pathway. In vivo, treatment with the aptamer-functionalized ApoV microneedle system significantly improved muscle mass, myofiber cross-sectional area, mitochondrial oxidative capacity, and functional endurance in sarcopenic mice compared with controls.Conclusions Our findings demonstrate that the muscle-targeted delivery of engineered ApoVs via HAMA microneedles effectively reverses key hallmarks of sarcopenia by restoring mitochondrial homeostasis and activating PI3K/AKT signaling through miR-21-5p. This microneedle-based ApoV platform provides a promising cell-free therapeutic strategy for ameliorating muscle atrophy and functional decline.
SN - 1477-3155
ER -