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

• 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
• ISSN: 0142-9612; 1878-5905; 1878-5905
• DOI: 10.1016/j.biomaterials.2024.122700

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.