负载SDF-1的羟基磷灰石纳米带/聚乳酸“双面神”复合膜促进牙周再生的研究

屏障膜作为引导组织再生的关键材料，决定着牙周再生效果。但目前的屏障膜主要起阻挡作用，开发具有生物活性的屏障膜是牙周再生研究的前沿方向。本项目首次通过对羟基磷灰石(HAp)与聚乳酸(PLA)进行可控组装，构建负载SDF-1的HAp/PLA“双面神”复合膜，一张膜两个功能面发挥屏障阻挡、干细胞募集、免疫反应调控和骨诱导等作用：疏水性PLA作为屏障维持再生空间；亲水性HAp利于细胞附着，促进成骨分化；缓释的SDF-1募集干细胞、促血管生成；SDF-1和HAp均可调控巨噬细胞向M2型极化，减轻炎症反应，协同促进组织再生。本项目拟通过体外实验探讨复合膜对牙周膜干细胞（PDLSCs）增殖、迁移和成骨分化的影响；对巨噬细胞极化的影响和在免疫反应中作用；将复合膜用于体内牙周创区，探讨对干细胞募集、免疫反应及牙周再生的作用。该项目旨在为牙周病治疗提供新的治疗策略和全新概念的复合屏障膜，从而优化牙周再生技术。

As the key material of guided tissue regeneration, barrier membrane plays important roles in determining the outcome of periodontal regeneration. At present, barrier membrane only has the effect of barrier isolation. The development of barrier membrane with bioactivity has become the hotspot and frontier direction of periodontal regeneration. Our project firstly proposes to construct stromal cell derived factor-1 (SDF-1) loaded hydroxyapatite (HAp) nanobelt/polylactic acid (PLA) Janus membrane for promoting periodontal regeneration by controllable assembly method. This HAp/PLA Janus membrane with two functional sides can act as barrier membrane, recruit stem cells, regulate immune reaction and induce bone formation. The underneath mechanisms involve the following aspects: hydrophobic PLA side acts as a barrier to provide space for effective regeneration; hydrophilic HAp nanobelt side facilitates cell attachment, osteogenic differentiation and participates in bone formation as bone source; the sustained release of SDF-1 recruits stem cells to the defect site in the early stage of wound healing and enhances angiogenesis; both SDF-1 and HAp can stimulate M2 polarization of macrophages, alleviate inflammation and synergistically enhance tissue regeneration. This project aims to explore the effects of this Janus membrane on the proliferation, migration and osteogenic differentiation of periodontal ligament stem cells (PDLSCs); to evaluate the effects of this Janus membrane on the polarization of macrophages and on the host immune response; to investigate the effects of this Janus membrane on stem cells engraftment, immune reaction and periodontal regeneration by creating a rat periodontal defect in vivo. This project will provide a new strategy and a novel combined membrane for periodontal therapy, therefore to optimize periodontal tissue regeneration technique.