双层水凝胶的制备及其对糖尿病创面炎症调控行为的影响

Preparation of bilayer hydrogel and its influence on inflammation modulation in diabetic wounds

糖尿病溃疡是临床常见的慢性难愈创面,以炎症失调为主要病理生理特征。当前,针对糖尿病溃疡创面的研究多关注后期抗炎治疗,较少研究早期炎症响应对糖尿病创面愈合的影响。针对上述问题,以胶原和氧化透明质酸为基质构建仿生皮肤结构的双层水凝胶。该双层水凝胶的下层具有疏松孔结构,用于负载和快速释放神经肽P物质(SP);上层具有较致密的孔结构,用于负载和控制释放白细胞介素10(IL-10)。通过顺序释放SP和IL-10,以期达到调控创面炎症反应并促进慢性伤口愈合的目的。研究表明,负载SP和IL-10的双层水凝胶在炎症早期显著提高中性粒细胞在伤口处的浸润数量,并在损伤后第6 d促进M1型巨噬细胞向M2型转化,从而启动炎症消退和组织修复过程,最终实现创面愈合。

Diabetic ulcer is a common chronic and refractory wound in clinic,which features inflammation dysregulation.The present researches mainly focus on anti-inflammatory treatment in the late stage of inflammation,while less focus on the effects of early inflammation response on the wound healing.In light of this,inspired by the structure of natural skin,a bilayer hydrogel was fabricated using gelatin and oxidized hyaluronic acid as the matrices.By adjusting the microstructure of the bilayer hydrogel,the bottom layer possessed looser pore structure and was applied for the loading and fast release of substance P;the top layer had denser pore structure and was used for the loading and delayed release of interleukin-10.The sequential release of SP and IL-10 is aimed at modulating the wound inflammatory response to promote chronic wound healing.The results show that the SP/IL-10-loaded bilayer hydrogel promotes the neutrophil infiltration in wounds at the early phase of inflammation,and promotes the transition of M1 macrophages to M2 macrophages at 6 days post-wound,thereby facilitating the inflammation resolution and wound healing.