细菌纤维素梯度界面层的构建与骨软骨再生行为的研究

The structure and performance of cartilage and subchondral bone layers in human joints are extremely different yet perfectly integrated. This is attributed to the presence of an impermeable interface layer (i.e., calcified cartilage layer) between them. However, the interface layer is very thin and complicated with gradient morphology and chemical compositions. Therefore, limited progress has been made in constructing a biomimetic gradient interface layer in osteochondral tissue engineering scaffolds and little is known about the relationship between the gradient characteristics of interface layer and the osteochondral regeneration. To this end, this project will construct an in situ “impermeable” gradient interface layer by making full use of the prominent advantage of bacterial cellulose (namely dense nanofibrous structure). This project aims to construct gradient interface layer and entirely integrated osteochondral scaffolds consisting of bacterial cellulose (polysaccharide), collagen, and hydroxyapatite (HAp) via membrane-liquid interface culture strategy and liquid flowing control method. The scaffolds will exhibit gradient pore structure and gradient chemical compositions (HAp, collagen, and growth factor). The regulation of the gradient feature parameters of the in situ grown interface layer will be investigated. The emphasis of the project will be placed on the interactions between gradient interface layer and cell/tissue. The in vivo osteochondral remodeling will also be investigated. The dependence of osteochondral regeneration on the characteristics of gradient interface layer will be disclosed. The results of this project may provide solid theoretical guidance and new methodology for the design and preparation of osteochondral scaffolds.

在人体关节骨软骨中，软骨层与软骨下骨层的结构和性能差异极大，却能完美整合，这归因于其间的界面阻隔层（即钙化软骨层）。然而，由于界面层极薄，且几何结构与化学组成极其复杂（呈梯度变化），致使人们难以在骨软骨支架中构建仿生梯度界面层，因而对界面层梯度特性与骨软骨再生之间的内在联系缺乏足够的认识。为此，本项目拟充分利用细菌纤维素（BC）纳米纤维支架结构致密的独特优势，原位构建具有“阻隔”功能的界面层，并采用膜液界面培养与液流控制技术制备由BC、胶原和羟基磷灰石（HAp）等组成的梯度（孔隙、HAp、胶原、生长因子）界面层及整体融合型骨软骨支架。本项目拟探索界面层梯度特性参数的调控规律，重点研究梯度界面层与细胞/组织的相互作用，考察体内骨软骨修复效果，揭示界面层梯度特性对骨软骨（尤其是界面层组织）再生过程的调控规律。本项目可望为具有仿生界面层的骨软骨支架的设计与制备提供可靠的理论依据和新的技术途径。

在人体关节骨软骨中，软骨层与软骨下骨层的结构和性能差异极大，却能完美整合，这归因于其间的界面阻隔层（即钙化软骨层）。然而，由于界面层极薄，且几何结构与化学组成极其复杂（呈梯度变化），致使人们难以在骨软骨支架中构建仿生梯度界面层，因而对界面层梯度特性与骨软骨再生之间的内在联系缺乏足够的认识。为此，本项目充分利用细菌纤维素（BC）纳米纤维支架结构致密的独特优势，原位构建了具有“阻隔”功能的界面层，并采用膜液界面培养等技术制备了由BC、胶原和羟基磷灰石（HAp）等组成的梯度（孔隙、HAp、胶原、生长因子）整体融合型骨软骨梯度支架。本项目拟探索梯度特性参数的调控规律，重点研究梯度结构与细胞/组织的相互作用，考察体内骨软骨修复效果，揭示梯度特性对骨软骨（尤其是界面层组织）再生过程的调控规律。本项目的研究成果可望为具有仿生界面层的骨软骨支架的设计与制备提供可靠的理论依据和新的技术途径。