Bioactive sucralfate-based microneedles promote wound healing through reprogramming macrophages and protecting endogenous growth factors

Impaired wound healing due to insufficient cell proliferation and angiogenesis is a significant physical and psychological burden to patients worldwide. Therapeutic delivery of exogenous growth factors (GFs) at high doses for wound repair is non-ideal as GFs have poor stability in proteolytic wound...

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Bibliographic Details
Published in:Biomaterials 2024-12, Vol.311, p.122700, Article 122700
Main Authors: Le, Zhicheng, Ramos, Mayk Caldas, Shou, Yufeng, Li, Renee R., Cheng, Hong Sheng, Jang, Clarisse JM, Liu, Ling, Xue, Chencheng, Li, Xianlei, Liu, Hong, Lim, Chwee Teck, Tan, Nguan Soon, White, Andrew D., Charles, Christopher John, Chen, Yongming, Liu, Zhijia, Tay, Andy
Format: Article
Language:English
Subjects:
Animals
Bioactive
Diabetes Mellitus, Experimental
Growth factors
Intercellular Signaling Peptides and Proteins - administration & dosage
Intercellular Signaling Peptides and Proteins - metabolism
Intercellular Signaling Peptides and Proteins - pharmacology
Interleukin-4 - metabolism
Macrophages - drug effects
Macrophages - metabolism
Male
Mice
Mice, Inbred C57BL
Microneedle
Needles
RAW 264.7 Cells
Sucralfate
Sucralfate - pharmacology
Swine
Wound healing
Wound Healing - drug effects
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Summary:Impaired wound healing due to insufficient cell proliferation and angiogenesis is a significant physical and psychological burden to patients worldwide. Therapeutic delivery of exogenous growth factors (GFs) at high doses for wound repair is non-ideal as GFs have poor stability in proteolytic wound environments. Here, we present a two-stage strategy using bioactive sucralfate-based microneedle (SUC-MN) for delivering interleukin-4 (IL-4) to accelerate wound healing. In the first stage, SUC-MN synergistically enhanced the effect of IL-4 through more potent reprogramming of pro-regenerative M2-like macrophages via the JAK-STAT pathway to increase endogenous GF production. In the second stage, sucralfate binds to GFs and sterically disfavors protease degradation to increase bioavailability of GFs. The IL-4/SUC-MN technology accelerated wound healing by 56.6 % and 46.5 % in diabetic mice wounds and porcine wounds compared to their respective untreated controls. Overall, our findings highlight the innovative use of molecular simulations to identify bioactive ingredients and their incorporation into microneedles for promoting wound healing through multiple synergistic mechanisms.
ISSN:0142-9612
1878-5905
1878-5905
DOI:10.1016/j.biomaterials.2024.122700