Microdroplet-mediated exosome delivery system for the therapeutic management of radiation-induced bone damage.
8 affiliations
- 1Department of Orthopaedic Surgery, The Eighth Affiliated Hospital of Southern Medical University (The First People's Hospital of Shunde), Foshan, Guangdong, 528308, China.
- 2Department of Epidemiology and Health Statistics, School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563000, China.
- 3Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, China.
- 4Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, China. [email protected].
- 5Department of Orthopaedic Surgery, The Eighth Affiliated Hospital of Southern Medical University (The First People's Hospital of Shunde), Foshan, Guangdong, 528308, China. [email protected].
- 6Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, China. [email protected].
- 7Zunyi Municipal Key Laboratory of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, China. [email protected].
- 8Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563003, China. [email protected].
Abstract
Radiation-induced skeletal deterioration and bone loss remain major clinical challenges. Although exosomes derived from human bone marrow-derived mesenchymal stromal cells (hBMSCs) (MSC-Exos) are promising cell-free therapeutics, their limited stability and low delivery efficiency hinder translational application. Here, we developed an innovative microdroplet-based exosome delivery platform (MD/Exos) and systematically evaluated its protective effects under irradiation-induced stress. MSC-Exos were successfully isolated and characterized using transmission electron microscopy and western blot analysis. Fluorescence imaging and confocal microscopy confirmed efficient uptake of MSC-Exos by both macrophages and hBMSCs. MD/Exos were fabricated by encapsulating exosomes within bovine serum albumin-stabilized microdroplets. Cytocompatibility assays showed that MD/Exos exhibited no detectable cytotoxicity toward macrophages. Functionally, MD/Exos significantly enhanced the viability, metabolic activity, and cytoskeletal integrity of irradiated hBMSCs. Notably, MD/Exos markedly promoted osteogenic differentiation after irradiation, as evidenced by increased alkaline phosphatase activity, enhanced mineralized matrix deposition, and upregulated osteogenesis-related gene expression. In parallel, MD/Exos modulated macrophage responses to radiation by suppressing aberrant multinucleated giant-cell formation and reducing pro-inflammatory cytokine expression. In vivo, administration of MD/Exos in an irradiation-induced bone injury model significantly attenuated bone loss and promoted bone regeneration, as evidenced by preserved bone microstructure, reduced osteoclast activity, and downregulated tumor necrosis factor-alpha (TNF-α) expression. Further in vivo cytokine analysis indicated that MD/Exos treatment significantly reduced pro-inflammatory cytokines compared to irradiated controls. Collectively, these findings demonstrate that MD/Exos represent a biocompatible and efficient exosome delivery platform capable of mitigating irradiation-induced cellular dysfunction, enhancing osteogenesis, and modulating immune-bone crosstalk. This study highlights the therapeutic potential of MD/Exos as a novel strategy for the prevention and treatment of radiation-induced bone loss.
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BibTeX
@article{zhang2026microdropletmediated,
title = {{Microdroplet-mediated exosome delivery system for the therapeutic management of radiation-induced bone damage.}},
author = {Yi Zhang and Wenqing Huang and Xianglin Peng and Haiping Lu and Yaping Ma and Ansu Wang and Xin Wang},
journal = {Journal of biological engineering},
year = {2026},
month = aug,
doi = {10.1186/s13036-026-00748-4},
url = {https://europepmc.org/article/MED/42972386},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Microdroplet-mediated exosome delivery system for the therapeutic management of radiation-induced bone damage.
AU - Yi Zhang
AU - Wenqing Huang
AU - Xianglin Peng
AU - Haiping Lu
AU - Yaping Ma
AU - Ansu Wang
AU - Xin Wang
PY - 2026
DA - 2026/08/06
JO - Journal of biological engineering
DO - 10.1186/s13036-026-00748-4
UR - https://europepmc.org/article/MED/42972386
AB - Radiation-induced skeletal deterioration and bone loss remain major clinical challenges. Although exosomes derived from human bone marrow-derived mesenchymal stromal cells (hBMSCs) (MSC-Exos) are promising cell-free therapeutics, their limited stability and low delivery efficiency hinder translational application. Here, we developed an innovative microdroplet-based exosome delivery platform (MD/Exos) and systematically evaluated its protective effects under irradiation-induced stress. MSC-Exos were successfully isolated and characterized using transmission electron microscopy and western blot analysis. Fluorescence imaging and confocal microscopy confirmed efficient uptake of MSC-Exos by both macrophages and hBMSCs. MD/Exos were fabricated by encapsulating exosomes within bovine serum albumin-stabilized microdroplets. Cytocompatibility assays showed that MD/Exos exhibited no detectable cytotoxicity toward macrophages. Functionally, MD/Exos significantly enhanced the viability, metabolic activity, and cytoskeletal integrity of irradiated hBMSCs. Notably, MD/Exos markedly promoted osteogenic differentiation after irradiation, as evidenced by increased alkaline phosphatase activity, enhanced mineralized matrix deposition, and upregulated osteogenesis-related gene expression. In parallel, MD/Exos modulated macrophage responses to radiation by suppressing aberrant multinucleated giant-cell formation and reducing pro-inflammatory cytokine expression. In vivo, administration of MD/Exos in an irradiation-induced bone injury model significantly attenuated bone loss and promoted bone regeneration, as evidenced by preserved bone microstructure, reduced osteoclast activity, and downregulated tumor necrosis factor-alpha (TNF-α) expression. Further in vivo cytokine analysis indicated that MD/Exos treatment significantly reduced pro-inflammatory cytokines compared to irradiated controls. Collectively, these findings demonstrate that MD/Exos represent a biocompatible and efficient exosome delivery platform capable of mitigating irradiation-induced cellular dysfunction, enhancing osteogenesis, and modulating immune-bone crosstalk. This study highlights the therapeutic potential of MD/Exos as a novel strategy for the prevention and treatment of radiation-induced bone loss.
SN - 1754-1611
ER -