基于FFC钛和有序电纺丝的骨-韧带锚定结构的仿生构建

Lack of the loading force resistance system and biological seal around implant surface in contrast to natural periodontium, titanium implants are still far from perfect substitutes for nature teeth. In this project, our long term goal is to reconstruct periodontal like tissue around titanium implant using tissue engineering strategy. A "titanium-bone-ligament" strategy will be used in this study to mimic the natural "tooth-cementum-ligament" structure, based on the highly chemical/biological similarity between bone and cementum. Focusing on the bone-ligament anchorage, Sharpey's fibers are going to be reconstructed inserting into the bone tissues around implant surface. To mimic this natural system, an oriented electrospinning nanofibrous scaffold will be developed inserting into the adherent coating on the surface of porous titanium implant. Simultaneously, specific growth factors will be incorporated into both fibrous scaffold and adherent coating to guide bone/ligament formation and interaction. Furthermore, gene modified periodontal ligament progenitor cells will be seeded on the scaffold in vitro and in vivo to test the efficacy of the system. In addition, the resistance function of this construct will be tested in a stress loading circumstance. The obtained knowledge from this study will contribute to classify the possibility to construct a biological natural mimicking dental implant for clinical application.

骨结合种植体虽然在临床上取得了成功，但并不是最理想的天然牙替代者，因为骨结合种植体缺乏牙周组织的应力缓冲和生物封闭的保护作用。构建种植体周的牙周样组织可以更好地模拟天然牙的功能。"种植体-牙骨质-韧带-骨"结构是以往研究采用的策略。本课题将以构建"种植体-骨-韧带-骨"结构为目的，并主要以"骨-韧带"锚定结构为研究重点。这是基于牙骨质和牙槽骨都是通过sharpey's纤维锚定牙周韧带，骨与牙骨质在分子和细胞水平上有极高相似性，而且种植体-骨具有成熟的理论和临床基础。本研究将以基因修饰的牙周干细胞为种子细胞，在具有粘附分子涂层的熔岩电脱氧法制成的多孔钛种植体表面，利用可程序化释放多种生长因子的纳米电纺丝定向纤维支架，构建种植体周"骨-韧带"锚定结构，并在微应力环境中研究锚定结构的形成和改建。本项目将为种植体周牙周样组织的形成提供实验依据，并为研究更加仿生化的新型种植体打下坚实基础。

本课题针对种植体骨性结合缺乏牙周组织应力缓冲易致应力集中和机械损伤并发症的缺陷，拟构建“种植体-骨-韧带-骨”结构，并着重研究“骨-韧带“锚定结构。首先制备并实现抗菌、骨结合性能优化的FFC钛，随后利用PLGA-PCL静电纺丝支架实现牙槽骨及牙周膜再生，同时研究证实白血病抑制因子(LIF)可以有效抑制低氧低血清诱导的干细胞凋亡，并能抑制牙周炎，为后续在体内实现”骨-韧带“锚定型种植体提供有利于骨结合，抗凋亡及预防种植体周围炎的基础。.项目在研期间完成如下工作：.1、制备并优化适用于构建骨-韧带锚定结构的FFC钛；.2、为提高钛的抗菌性能及骨结合性能，通过低温电沉积技术在钛表面形成载有四环素/镁离子/铜离子-壳聚糖/明胶纳米涂层；.3、利用三维PLGA-PCL静电纺丝支架材料结合预诱导软骨分化的间充质干细胞实现牙槽骨及牙周膜的再生；.4、研究并发现白血病抑制因子（LIF）可抑制低氧低血清环境所诱导的干细胞凋亡；.5、研究并发现LIF可抑制牙周炎的骨吸收、胶原破坏及炎症因子表达。