具有缓释纳米银功能的PGA网-胶原真皮支架介导M2型巨噬细胞活化促进创面修复机制的相关研究

The advent of dermal substitutes provides a revolutionary strategy for the repair and reconstruction of deep skin defects. While these products could be taken full advantage for the foreign body reaction. Silver nanoparticles have been widely used in various kinds of wound treatment with excellent anti-inflammation effect, but its mechanism is still unclear. Macrophages throughout the wound repair process are key cells in wound healing. Thus macrophages as potential target cells of silver nanoparticles. In this research we developed a novel NAg-PGAm-collagen hybrid scaffold (NAg-PCS ) using the sonochemical technique with function of slow release of NAg for burn wound healing applications. The M2 macrophage activation of silver nanoparticles was studied. What’s more, the fibroblast cell behavior was also observed through the three-dimensional co-culture with macrophages in the scaffold. The compatibility and foreign body reactions were evaluated by using a subcutaneous implantation model in mice. To characterize the effects of NAg-PCS on tissue regeneration and related mechanism of M2 type macrophages activation, dermal substitutes were transplanted to repair full-thickness skin wounds in Sprague-Dawley rats.

组织工程真皮产品是目前治疗大面积皮肤缺损的有效手段，但是由于异物植入后的炎症及烧伤等特殊创面的异常炎症反应，阻碍了该类真皮替代物的临床运用。纳米银长期用于烧伤创面，我们前期研究证明，纳米银不仅具有抗菌作用，同时具有抗炎作用。我们猜想将纳米银引入组织工程皮肤势必会改善材料植入后的炎症反应。本研究我们利用超声化学技术制备能够缓释纳米银的胶原-PGA网支架，体外研究纳米银及该支架对M2型巨噬细胞的活化作用，并探索活化后的巨噬细胞对成纤维细胞的行为影响。体内通过小鼠皮下埋置模型评估PGA网—胶原支架的异物炎症反应情况改善与M2巨噬细胞活化的相关性，并通过烧伤创面真皮支架移植，研究该支架促进创面修复的效果及通过JAKl／3-STAT6信号转导通路介导M2型巨噬细胞活化促进支架诱导组织再生的相关机制。

组织工程真皮产品是目前治疗大面积皮肤缺损的有效手段，但是由于异物植入后的炎症及烧伤等特殊创面的异常炎症反应，阻碍了该类真皮替代物的临床运用。纳米银长期用于烧伤创面，我们研究证明，纳米银不仅具有抗菌作用，同时具有抗炎作用。因此我们将纳米银引入组织工程皮肤，改善了材料植入后的炎症反应。本研究我们利用超声化学技术制备能够缓释纳米银的胶原-PGA网支架，通过体内及体外研究了纳米银及该支架对M2型巨噬细胞的活化作用，并证实该作用可以明显改善烧伤后创缘进行性坏死的发生，有利于创面的修复。体内通过小鼠皮下埋置模型证实了引入纳米银的PGA网—胶原支架的在小鼠体内没有明显的异物炎症反应情况改善，且该机制也与M2巨噬细胞活化的相关。在小型猪背部创面移植试验中，我们证实含纳米银的真皮支架可以明显诱导真皮再生，不仅没有感染，且可以通过对创面炎症及巨噬细胞活化的影响来加快创面的愈合和修复。