Mariya M.J. Elakkawi, Yingjie Zhu, Yang Xiong, Changhong Li, Hantao Li, Jianwei Chen, Tao Xu, Xiangdong Qi
This work demonstrates 3D-exosome/HAMA synergy in resolving inflammation-angiogenesis imbalance, offering a clinically promising strategy for burn regeneration. • Novel 3D hUCMSC-exosome microneedles (EXO@HAMA) enable sustained wound repair. • EXO@HAMA microneedles boost burn healing (98.5 % closure) and cut CD68 + macrophages by 83.6 %. • Synergizes Wnt/β-catenin, lipid metabolism, and CTSB inhib
Burn wound healing remains challenging due to uncontrolled inflammation and poor angiogenesis. We developed hyaluronic acid methacryloyl microneedles (EXO@HAMA) loaded with 3D-cultured mesenchymal stem cell (MSC) exosomes to overcome limitations of growth factor therapies and sudden release of exosomes. 3D-exosomes potently enhanced fibroblast proliferation and endothelial tube formation. In rat deep second-degree burns, EXO@HAMA reduced inflammation and accelerated healing through CTSB/TGF-β and Wnt/β-catenin axis modulation, significantly improving collagen deposition and angiogenesis. Transcriptomics revealed activation of lipid metabolism and extracellular matrix (ECM) remodeling. This work demonstrates 3D-exosome/HAMA synergy in resolving inflammation-angiogenesis imbalance, offering a clinically promising strategy for burn regeneration. • Novel 3D hUCMSC-exosome microneedles (EXO@HAMA) enable sustained wound repair. • EXO@HAMA microneedles boost burn healing (98.5 % closure) and cut CD68 + macrophages by 83.6 %. • Synergizes Wnt/β-catenin, lipid metabolism, and CTSB inhibition for ECM remodeling. • CTSB inhibition elevates TGF-β1/β2, enhancing ECM via COL1A1 alignment and integrin signaling. • Sustained exosome-lipid release in microneedles surpasses growth factors in regeneration.