Abstract：
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.
摘要：
由于细胞增殖和血管生成不足而导致的伤口愈合受损是全世界患者的重大生理和心理负担。用于伤口修复的高剂量的外源性生长因子(GF)的治疗性递送是不理想的,因为GF在蛋白水解伤口环境中具有差的稳定性。这里,我们提出了一种两阶段策略,使用基于硫糖铝的生物活性微针(SUC-MN)递送白细胞介素-4(IL-4)以加速伤口愈合.在第一阶段,SUC-MN通过经由JAK-STAT途径更有效地重编程促再生M2样巨噬细胞以增加内源性GF产生来协同地增强IL-4的作用。在第二阶段,硫糖铝与GFs结合，并在空间上不利于蛋白酶降解，以增加GFs的生物利用度。与各自未处理的对照相比,IL-4/SUC-MN技术在糖尿病小鼠伤口和猪伤口中加速伤口愈合56.6%和46.5%。总的来说,我们的研究结果强调了创新使用分子模拟来识别生物活性成分,并将其掺入微针中,通过多种协同机制促进伤口愈合.
