“超分子-杂化”双体系构建新型可注射水凝胶及其用于软骨修复的研究

Minimally invasive treatment of cartilage defects becomes one of the most important strategies for modern orthopedics development. Injectable biomaterials are promising for minimally invasive surgery. However, unsatisfactory mechanical strength and the difficulty in the immobilization into tissue defects limit the clinical application of injectable materials. Therefore, this project aims at the fabrication of cartilage-regenerating hydrogels with strong stickiness, in addition, at resolving the contradiction between high toughness/strength and injectability. In our early work a host-guest complexation between monoacrylated β-cyclodextrin and benzene rings of gelatin (supramolecular system) was applied to fabricate a self-repairing injectable hydrogel, which showed strong stickiness and great effect of cartilage regeneration. For the purpose of further optimizing the mechanical properties of such supramolecular hydrogel, an inorganic silica network is introduced by use of a silane coupling agent to achieve an inorganic-organic hybridization (hybrid system). This is expected to enhance the hydrogel strength mechanically and therefore to create a novel injectable hydrogel with high toughness and strength. In this study, the influence of molecular structures on the gelatin behavior and properties of hydrogel will be systematically investigated, which will reveal the interaction mechanism of supramolecular-hybrid dual system and the effects of various compositions on hydrogel performances. Furthermore, in vitro and in vivo experiments will be performed as follows: bone marrow derived mesenchymal stem cells combined with the novel hydrogels will be induced to be chondrocytes and form a tissue-engineered cartilage, which will subsequently be used for the treatment of animal cartilage defects. This project is expected to lay the foundation for the design of a cartilage-regenerating hydrogel that can satisfy the clinical requirements.

微创治疗软骨缺损是现代骨科发展的重要方向之一，可注射型材料为微创手术提供优良的治疗载体。然而其力学性能不佳或易从缺损部位流失，极大限制其临床应用。研制高粘性软骨修复水凝胶，解决凝胶强韧性与可注射性之间的矛盾是本项目的目标。申请人前期采用单丙烯酰化β-环糊精与明胶分子上的苯环主客体结合（超分子体系），构建出具有较强组织粘附性和软骨修复效果的自修复可注射水凝胶，但其力学强度有待改进。鉴于此，本项目拟通过硅烷偶联剂以分子杂化形式引入无机硅网络（杂化体系），提高超分子水凝胶强度，糅合两种共存体系的优势，构筑力学强韧的可注射水凝胶。通过系统研究材料分子结构对凝胶行为及力学和注射性等重要性能的影响，揭示超分子-杂化双体系相互作用的机理，阐明不同组分比例对凝胶性能的调控规律；探讨凝胶复合骨髓间充质干细胞体外成软骨的效果并评估其修复动物软骨缺损的疗效。本项目有望为设计符合临床需求的软骨修复水凝胶奠定基础。

微创治疗软骨缺损是现代骨科发展的重要方向之一，可注射型材料为微创手术提供优良的治疗载体。然而其力学性能不佳或易从缺损部位流失，极大限制其临床应用。研制高粘性软骨修复水凝胶，解决凝胶强韧性与可注射性之间的矛盾是本项目的目标。项目负责人前期采用单丙烯酰化β-环糊精与明胶分子上的苯环主客体结合（超分子体系），构建出具有较强组织粘附性和软骨修复效果的自修复可注射水凝胶，但其力学强度有待改进。鉴于此，本项目通过硅烷偶联剂以分子杂化形式引入无机硅网络（杂化体系），提高超分子水凝胶强度，糅合两种共存体系的优势，构筑出力学强韧的可注射水凝胶。通过调控凝胶合成过程中所涉及到的各种参数（主-客体分子比例、无机/有机比例、偶联剂含量、反应温度等），使该新型水凝胶继承了超分子水凝胶良好的自愈性、组织粘附性和细胞相容性，具备了一定的可注射能力。同时，“超分子-杂化”双体系水凝胶展现出远比超分子水凝胶优越的力学性能，具有良好的力学强度与韧性。通过凝胶复合骨髓间充质干细胞构建组织工程化软骨并进行兔子关节软骨缺损修复实验，发现实验组中软骨缺损得到一定修复，而空白对照组则未见明显修复。本项目有望为设计符合临床需求的软骨修复水凝胶奠定基础。