炎症及纤维化严重制约着组织器官再生过程。申请人前期研究发现替代激活巨噬细胞（M2）有望促进多向排列的牙周膜纤维重建，有利于咀嚼功能恢复。然而，某些M2亚型的存在也可能导致病理性纤维化形成；此外，尚未建立M2巨噬细胞的高效激活体系。双聚合物的功能化氧化石墨烯作为一种新型纳米载体材料，不仅可以降低活性氧释放、抑制炎症反应，又可以负载特定基因诱导M2巨噬细胞分化，促进组织修复。本项目拟首先采用纳米级的双功能化氧化石墨烯作为质粒载体，分别特异性激活组织修复相关M2巨噬细胞亚型（M2a、M2c），然后比较两种亚型在调控牙囊细胞向牙周形成细胞分化的不同，通过RNA-seq筛选相关差异基因及信号蛋白，探索促功能性牙周组织再生的调控蛋白。进一步以大鼠牙周组织缺损模型及牙缺失模型评价M2a、M2c在牙周组织再生中的调控作用，旨在探索特异性高效激活的M2巨噬细胞亚型用于促进损伤组织功能性修复，避免纤维化形成。

Functional tissue or organ regeneration is usually compromised by inflammation and fibrosis. Activation of alternative macrophages (M2) has emerged as a key area of resolving inflammation, controlling tissue homeostasis and disease pathogenesis. Our preliminary studies indicated that locally activated M2 macrophage facilitated periodontium complex-like tissues reconstruction in a dentition defect model of nonhuman primates. However, it is reported that some nomenclature of M2 subsets might be associated with pathological fibrosis, and it is difficult to preserve the bioactivity of the delivered proteins for macrophage activation in vivo. Dual-functionalized GO derivative could serve as an antioxidant and an effective gene carrier for M2 macrophage polarization. The present study construct gene delivered graphene oxide system targeting M2a/M2c polarization, and compare the effect of M2a or M2c on the cementoblastic/osteoblastic/fibroblastic differentiation of dental follicle cell sheets. In order to explore targeted genes regulating functional periodontal regeneration, the related gene expression and signaling pathway are analyzed by RNA-seq. Models of periodontal fenestration defects and tooth dentition defects in Rats are constructed to evaluate the effect of M2 subsets on modulating periodontal tissue regeneration. Our project aims to promote functional tissue repair without fibrosis by modulating appropriate M2 subsets.