Mechano-Activated Cell Therapy for Accelerated Diabetic Wound Healing.

Autor: Shou Y; Department of Biomedical Engineering, National University of Singapore, Singapore, 117583, Singapore.; Institute for Health Innovation & Technology, National University of Singapore, Singapore, 117599, Singapore., Le Z; Department of Biomedical Engineering, National University of Singapore, Singapore, 117583, Singapore.; Institute for Health Innovation & Technology, National University of Singapore, Singapore, 117599, Singapore., Cheng HS; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore., Liu Q; School of Civil Engineering and Architecture, Wuhan University of Technology, Wuhan, 430070, China., Ng YZ; Skin Research Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, 308232, Singapore., Becker DL; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore.; Skin Research Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, 308232, Singapore., Li X; Department of Biomedical Engineering, National University of Singapore, Singapore, 117583, Singapore.; Institute for Health Innovation & Technology, National University of Singapore, Singapore, 117599, Singapore., Liu L; Institute for Health Innovation & Technology, National University of Singapore, Singapore, 117599, Singapore.; NUS Tissue Engineering Program, National University of Singapore, Singapore, 117510, Singapore., Xue C; Department of Biomedical Engineering, National University of Singapore, Singapore, 117583, Singapore.; Institute for Health Innovation & Technology, National University of Singapore, Singapore, 117599, Singapore., Yeo NJY; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore., Tan R; School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou, 510006, China., Low J; Department of Biomedical Engineering, National University of Singapore, Singapore, 117583, Singapore., Kumar ARK; Institute for Health Innovation & Technology, National University of Singapore, Singapore, 117599, Singapore.; Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119288, Singapore., Wu KZ; Department of Biomedical Engineering, National University of Singapore, Singapore, 117583, Singapore., Li H; School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore, 639798, Singapore., Cheung C; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore.; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, 138648, Singapore., Lim CT; Department of Biomedical Engineering, National University of Singapore, Singapore, 117583, Singapore.; Institute for Health Innovation & Technology, National University of Singapore, Singapore, 117599, Singapore.; Mechanobiology Institute, National University of Singapore, Singapore, 117411, Singapore., Tan NS; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore.; School of Biological Sciences, Nanyang Technological University, Singapore, 637551, Singapore., Chen Y; School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou, 510006, China., Liu Z; School of Materials Science and Engineering, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, Sun Yat-sen University, Guangzhou, 510006, China., Tay A; Department of Biomedical Engineering, National University of Singapore, Singapore, 117583, Singapore.; Institute for Health Innovation & Technology, National University of Singapore, Singapore, 117599, Singapore.; NUS Tissue Engineering Program, National University of Singapore, Singapore, 117510, Singapore.
Jazyk: angličtina
Zdroj: Advanced materials (Deerfield Beach, Fla.) [Adv Mater] 2023 Nov; Vol. 35 (47), pp. e2304638. Date of Electronic Publication: 2023 Oct 19.
DOI: 10.1002/adma.202304638
Abstrakt: Chronic diabetic wounds are a significant global healthcare challenge. Current strategies, such as biomaterials, cell therapies, and medical devices, however, only target a few pathological features and have limited efficacy. A powerful platform technology combining magneto-responsive hydrogel, cells, and wireless magneto-induced dynamic mechanical stimulation (MDMS) is developed to accelerate diabetic wound healing. The hydrogel encapsulates U.S. Food and Drug Administration (FDA)-approved fibroblasts and keratinocytes to achieve ∼3-fold better wound closure in a diabetic mouse model. MDMS acts as a nongenetic mechano-rheostat to activate fibroblasts, resulting in ∼240% better proliferation, ∼220% more collagen deposition, and improved keratinocyte paracrine profiles via the Ras/MEK/ERK pathway to boost angiogenesis. The magneto-responsive property also enables on-demand insulin release for spatiotemporal glucose regulation through increasing network deformation and interstitial flow. By mining scRNAseq data, a mechanosensitive fibroblast subpopulation is identified that can be mechanically tuned for enhanced proliferation and collagen production, maximizing therapeutic impact. The "all-in-one" system addresses major pathological factors associated with diabetic wounds in a single platform, with potential applications for other challenging wound types.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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