组织修复是局部组织、细胞因致病因素导致损伤和死亡后，由新的细胞再生来修补顶替，以恢复组织完整性的过程。组织修复的目的是恢复创伤组织的结构和功能，其本质是重建组织发育的过程。近年来,仿生水凝胶在组织修复领域展现出了独特的优势。本文从生物体的精细结构出发，结合水凝胶的独特优势，探索了异质水凝胶在组织修复中的应用。首先，开发了新型的拉伸策略，设计并制备了一种微观异质水凝胶材料，该水凝胶材料在体外成功诱导心肌细胞恢复原有的有序结构，实现了急性心肌梗死心肌组织的修复。为了精确控制组织修复过程，制备了基于微流控芯片技术的介观异质水凝胶材料，证明了三种因子浓度梯度在脑损伤修复中作用，实现了脑组织的修复。此外，开发了一种具有粘附层和剪切力响应耗散层的宏观异质水凝胶材料，该水凝胶材料具有优异的广谱粘附性能和响应脱粘附的性能，实现了急性肝损伤的免缝合止血，减少了组织修复过中的二次损伤，促进了组织愈合。本论文的主要研究成果概括如下：（1）将聚吡咯纳米管复合到海藻酸钙-丙烯酰胺双网络水凝胶中，通过反复的弹性拉伸，制备了一种导电异性的水凝胶材料。该复合水凝胶继承了原有双网络水凝胶的优秀机械性能。体外和体内生物学评价证明了该材料能够诱导原代分离的心肌细胞定向生长，并治疗急性心肌梗死。（2）通过“三入口”的“圣诞树”结构微流控芯片制备了三因子（迁移诱导因子Sema3A、促进增殖的碱性成纤维细胞生长因子FGF2和分化诱导因子DAPT）独立浓度梯度的水凝胶。通过荧光溶液模拟证明了梯度微流控的有效性。体内和体外生物学评价证明了该材料在脑组织修复中的作用。（3）以儿茶酚修饰的壳聚糖作为粘附层，将触变分子N-芴甲氧羰基-L-色氨酸与海藻酸钙-丙烯酰胺双网络复合作为耗散层，制备了具有双层结构的响应脱粘附的粘附水凝胶材料。体外实验证明了该介观异质水凝胶具有广谱的粘附性能和响应脱粘附能力。体外和体内生物学评价证明了其具有优秀的生物相容性。急性肝损伤的动物模型实验证明了该水凝胶具有快速止血的能力，并能够促进组织愈合。
Organisms with fine structures whose size varies from molecular to macro scale, undertake complex functions in vivo. The purpose of tissue repair is to restore the structure and function of traumatic tissue. Many tissue structures in the human body are long-range ordered. In this paper, we designed a simple and novel stretching strategy to prepare a micro-heterogeneous hydrogel material, which successfully induced the recovery of the ordered myocardial tissue in vitro. The essence of tissue repair is to reconstruct the process of tissue development, which is regulated precisely by various factors. Various factors have gradients distributed along the axis, which is a common feature of organisms. Based on microfluidic chip technology, we prepared gradient-controlled mesoscopic heterogeneous hydrogel materials by rapid gelation of fluid, and demonstrated their role in brain injury repair; In addition, suture-free is necessary to reduce secondary damage in various tissue engineering. In some application scenarios, it is also necessary to respond to deadhesion. Therefore, we developed a macroscale-heterogeneous hydrogel material with adhesive layer and shear-responsive dissipative layer, and proved its adhesion and responsive deadhesion performance. The main research results of this paper are summarized as follows: (1) Through the integration of polypyrrole nanotube and calcium alginate acrylamide double network hydrogel, a conductive anisotropic hydrogel was prepared by repeated elastic stretching. The above composite hydrogel exhibited excellent mechanical properties of typical original double network hydrogel. In vitro and in vivo experiments demonstrated that the material can induce the directional growth of primary isolated cardiomyocytes and treat acute myocardial infarction.(2) A ‘Christmas tree’ microfluidic chip with three entrances was designed to prepare the hydrogel with independent concentration gradient of three factors (migration inducing factor Sema3A, promoting the proliferation of basic fibroblast growth factor, and differentiation-inducing substance DAPT). The effectiveness of gradient microfluidics is demonstrated by fluorescence solution simulations. In vivo and in vitro experiments demonstrated its role in brain tissue repair.(3) A double-layered mesoscopic heterogeneous hydrogel with adhesion and deadhesion properties were prepared. Catechol modified chitosan was used to build an adhesive layer, the thixotropic molecule: n-fluorene methoxycarbonyl-l-tryptophan and calcium alginate acrylamide were integrated to build a double-network dissipative layer. Further experiments showed this hydrogel has excellent adhesion-responsive deadhesion ability and cytocompatibility. In addition, this hydrogel has the ability of fast hemostasis and can promote tissue healing in the animal model of acute liver injury.
