仿贻贝自修复组织诱导性水凝胶用于软骨/软骨下骨一体化修复机理研究

Articular bone/cartilage defects are very common in clinics, however, the current available biomaterials for the repair of cartilage defects can not fully satisfy the clinical requirement. This proposed project intends to develop mussel-inspired self-healable and tissue inductive hydrogels for osteochondral repair. Gelatin and dopamine are the main components of the hydrogel...Firstly, gelatin methacrylate (GelMA) is synthesized by adding methacrylate groups to the amine-containing side-groups of gelatin, which becomes photocrosslinkable. Secondly, dopamine methacrylamide (DMA) is also obtained through the similar route. Finally, the hydrogel is obtained through free-radical polymerization by exposing the GelMA and DMA to UV light. Dopamine imparts hydrogel with self-healing capability and tissue adhesiveness, and it also promotes adhesion of cells and tissue. Gelatin in the hydrogel carries the advantages that are representative characters of natural biomaterials, and can degrade after tissue repair is achieved. Hydroxyapatite nanoparticles (nHA) will also be incorporated. The hydrogel combines the characteristics of double-network hydrogels and nanocomposite hydrogels.. .The hydrogel is comprised of two layers. The upper layer contains transforming growth factor-beta (TGF-beta) that promotes cartilage regeneration. The TGF-beta is encapsulated in BSA nanoparticles, which protect growth factors from deactivation during polymerization process and realize the sustained release of the growth factors. The lower layer contains nHA, and can be used to repair the subchondral bone because of the osteoconductivity of nHA. Thus, the hydrogel can repair the cartilage / subchondral bone defects with one single unit. The biological performance of the hydrogel will be evaluated through the in vitro cell culture and in vivo implantation tests. ..This project will obtain synthetic routes of the hydrogel for the repair of osteochondral defects, and clarify the interaction mechanism between the hydrogel and cell / tissue. The expected results of this project will provide scientific basis for the design of next generation of hydrogel to treat osteochondral defects as a single unit. The success of the project will also be useful guidance for the development of biomedical engineering products in clinical applications.

软骨再生自修复能力差，关节软骨缺损修复是临床难题之一。水凝胶是一种潜在的软骨修复材料。现有水凝胶力学性能较差、缺少细胞亲和性和组织诱导性。本项目拟借鉴仿贻贝材料的粘附性和自修复性，在水凝胶体系中引入多巴胺功能团，结合双网络及纳米增强结构，研发用于骨/软骨修复的仿贻贝自修复组织诱导性水凝胶。该水凝胶由甲基丙烯酸酐化明胶与多巴胺聚合形成双交联网络，并复合生物活性纳米颗粒，预期具有优良的力学性能。多巴胺赋予水凝胶自修复功能及细胞亲和性/组织粘附性。该水凝胶分上下两层，上层负载转化生长因子，诱导软骨再生；下层含有纳米羟基磷灰石，诱导修复软骨下骨再生。期望得到兼具优良力学性能、自修复能力、细胞亲和性与组织诱导性的多功能双层水凝胶，实现一体化软骨/软骨下骨修复；揭示水凝胶结构与性能关系，阐明水凝胶与细胞/组织的相互作用及组织诱导机理。预期成果为关节软骨缺损修复提供新方法和新材料，为临床应用奠定基础。

软骨再生自修复能力差，关节软骨缺损修复是临床难题之一。水凝胶是一种潜在的软骨修复材料。现有水凝胶力学性能较差、缺少细胞亲和性和组织诱导性。本项目借鉴仿贻贝材料的粘附性，在水凝胶体系中引入多巴胺功能团，结合双网络及纳米增强结构，研发用于骨/软骨修复的仿贻贝组织诱导性水凝胶。以甲基丙烯酸酐改性的明胶（GelMA）为基体，引入聚多巴胺（PDA），并在水凝胶中原位矿化纳米钙磷相。通过调控多巴胺和钙磷的含量，优化水凝胶的物理化学性能。聚多巴胺赋予水凝胶细胞亲和性/组织粘附性。该水凝胶分上下两层，上层负载转化生长因子TGF-b，诱导软骨再生；下层含有纳米羟基磷灰石，诱导修复软骨下骨再生，是一种兼具优良力学性能、细胞亲和性与组织诱导性的多功能双层水凝胶。该水凝胶采用的一体化骨-软骨双层复合支架设计，省略了通常多层支架中缝合或粘接的步骤，从而使软骨部分与骨部分具有更加牢固、稳定的连接。该双层水凝胶可以一步植入到关节软骨缺损部位，实现一体化软骨/软骨下骨修复。研究结果揭示水凝胶结构与性能关系，阐明水凝胶与细胞/组织的相互作用及组织诱导机理。本项目的相关成果为软骨修复材料的设计制备提供科学依据，为实现关节软骨缺损的修复提供新材料和新方法，对提高关节软骨缺损的治疗水平，满足大量关节病患者的临床需求具有重要参考价值。