Light-stimulated smart thermo-responsive constructs for enhanced wound healing: A streamlined command approach

Bingcheng Yi , Lei Yu , Yating Yang , Carlos F. Guimarães , Ruijie Xu , Thavasyappan Thambi , Boya Zhou , Qihui Zhou , Rui L. Reis

Asian Journal of Pharmaceutical Sciences ›› 2025, Vol. 20 ›› Issue (4) : 101057

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Asian Journal of Pharmaceutical Sciences ›› 2025, Vol. 20 ›› Issue (4) :101057 DOI: 10.1016/j.ajps.2025.101057
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Light-stimulated smart thermo-responsive constructs for enhanced wound healing: A streamlined command approach

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Abstract

Efficient reconstruction of severe cutaneous wounds necessitates the orchestration of effective cell-mediated matrix remodeling and robust protection against microbial invasion. Herein, we engineered a near-infrared light (NIR)-stimulated, thermo-responsive bilayer system based on a drug-loaded hydrogel with a thermal-responsive temperature of ∼42 °C as the matrix layer and an antibacterial nanofibrous mat as the top layer. The matrix layer integrates basic fibroblast growth factor (bFGF)-loaded thermosensitive gelatin (Gel) hydrogel with polydopamine-Cu2+ coated short nanofibers (P@SF). Upon NIR exposure, P@SF elicits a photothermal effect, causing a rapid increase in temperature by 13.4 °C within 1 min at a power density of 0.75 W/cm2, which triggers the gel-sol transition of Gel and controls the release of bFGF. This, in turn, enhances fibroblast and endothelial cells ingrowth into the hydrogel, fostering cell functionalization and matrix remodeling. The top layer consists of poly(L-lactide-co-caprolactone) nanofibers functionalized with lysine-doped polydopamine and poly-l-lysine. It possesses antibacterial efficacy by isolating, controlling (76.23% for E. coli and 89.16% for S. aureus), and eliminating bacteria upon NIR activation. In rat skin wound models, this NIR-responsive smart bilayer system prevents S. aureus-mediated bacterial infection (indicative of reduced IL-6 expression), regulates CD31-positive neovascularization, and facilitates collagen remodeling for skin regeneration. In summary, this study introduces a novel strategy, inspired by the centralization of authority, for developing a smart thermo-responsive system with promising potential for the effective reconstruction of severe cutaneous wounds.

Keywords

Centralization of authority / Near-infrared light / Thermo-responsive hydrogel / Antibacterial nanofibers / Wound healing

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Bingcheng Yi, Lei Yu, Yating Yang, Carlos F. Guimarães, Ruijie Xu, Thavasyappan Thambi, Boya Zhou, Qihui Zhou, Rui L. Reis. Light-stimulated smart thermo-responsive constructs for enhanced wound healing: A streamlined command approach. Asian Journal of Pharmaceutical Sciences, 2025, 20(4): 101057 DOI:10.1016/j.ajps.2025.101057

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Conflicts of interest

The authors declare that there is no conflicts of interest.

Acknowledgments

The authors are very thankful for financial support by Shandong Provincial Natural Science Foundation (Grant No ZR2024QH150, ZR2024YQ068), Taishan Scholars Program of Shandong Province (Grant No tsqn202306272), National Natural Science Foundation of China (Grant No 82302388), National Key Research and Development Project of China (Grant No 2023YFFO715101), Qingdao Natural Science Foundation (Grant No 23-2-1-132-zyyd-jch), the Leading Project of Science and Technology of Yantai Development Zone (Grant No 2021RC016), National Key RD Program of China (2021YFF1201100), and Hubei Key Laboratory of Biomass Fibers & Eco-Dyeing & Finishing (Wuhan Textile University, Grant No STRZ202322).

Supplementary materials

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.ajps.2025.101057. The figures with "S" before the serial number are included in the Supplementary data.

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