IL-4诱导巨噬细胞表型转化促进仿生疝补片组织再生及相关机制的研究

With the increasing clinical demand for hernia patches, currently and widely used polymer composite hernia patches have some shortcomings, such as hernia recurrence, inflammatory response, abdominal adhesion, poor tissue regeneration and so on, are not suitable for individual treatment. Therefore, We are ready to develop biological hernia patches which have the function of promoting autologous tissue regeneration. According to reports, different phenotypes of macrophages have completely different biological behaviors. M1 macrophages mainly play a role in promoting the inflammatory reaction, M2 macrophages have the effect of inhibiting the inflammatory reaction and promoting tissue regeneration, and IL - 4 can induce macrophages transformed into M2 macrophages. In the early stage, we prepared biological material patches that simulated the components and structures of extracellular matrix,found that increased proportion of M2 macrophages when the period of tissue regeneration after patches transplantation. We verified IL-4 has the role of promoting transformation of macrophages to M2 phenotype at the same time. Based on the foundation of our research and related opinions of evaluation experts ,We use the natural collagen and chitosan by using electrostatic spinning technique to preparing bionic hernia patches and load IL-4 chitosan sustained release hydrogel. With the IL-4 slowly released , can induce autologous macrophages transform into M2 macrophages, increasing the proportion of M2 macrophages in tissues, so as to enhancing the extracellular matrix remodeling, reaching the role of promoting tissue regeneration. Preliminary exploration on the mechanism of M2 macrophages promoting tissue regeneration in vitro and vivo models.

临床上对疝补片的需求日益增多，目前广泛应用的高分子合成材料补片存在疝复发、炎症反应、脏器粘连、组织再生差等不足，已不适合个体化治疗的需要，因此我们拟研制具有促进自体组织再生功能的生物材料补片。据文献报道不同表型的巨噬细胞有不同的生物学行为，M1型巨噬细胞主要促进炎症反应，M2型巨噬细胞却抑制炎症反应并促进组织再生，而IL-4可诱导巨噬细胞向M2型转化。前期我们制备了仿细胞外基质的生物材料补片，发现其移植后组织再生时M2型巨噬细胞比例升高，并验证了IL-4具有促进巨噬细胞向M2型转化的作用。基于我们研究基础及评审专家意见，本项目以胶原、壳聚糖为原料用静电纺丝技术制备仿生疝补片，并负载IL-4壳聚糖缓释水凝胶。通过IL-4的缓慢释放，诱导自体巨噬细胞向M2型转化，提高组织中M2型巨噬细胞比例，从而增强细胞外基质重塑、促进组织再生。并通过体内外模型初步探索M2型巨噬细胞促进组织再生的机制。

随着腹股沟疝手术量的逐年升高，临床上对疝补片材料的需求量日益增多，而目前临床上广泛使用的合成材料补片存在疝复发、炎症反应以及相关脏器粘连等严重并发症，已不适合个体化治疗的需要，因此需要研发一种具有降解特性同时可以促进自体组织再生的功能化补片。.本项目研发了一种IL-4-胶原-聚己内酯复合疝补片，该补片是以天然胶原和可降解化合物聚己内酯为原料，利用高压静电纺丝技术制备三维网状结构疝补片，并在补片上负载IL-4壳聚糖缓释水凝胶。IL-4-胶原-聚己内酯复合疝补片具有良好的生物相容性和物理性能，可以满足体内移植的需求；同时补片上负载的水凝胶可以在体内缓慢释放IL-4以诱导自体巨噬细胞向M2型转化，以起到减轻炎症反应、促进自体组织再生的作用。.我们将IL-4-胶原-聚己内酯复合疝补片植入大鼠腹股沟疝模型，通过不同时间点取材检测，发现实验组（复合疝补片组）的组织相容性、炎症反应、自体组织再生及腹股沟疝修复情况均优于其他对照组。因此我们研发的IL-4-胶原-聚己内酯复合疝气补片有望克服目前临床上使用的疝气补片材料的的不足，为新型功能化补片的制备和应用提供了方法和思路。