可注射、自修复电活性纳米复合水凝胶的制备及其在心肌组织工程中的应用

Myocardial infarction accompanied with a large number of myocardial cell death has become a serious threat to human health. Because the cardiac cells are difficult to regenerate, the traditional clinical treatments can only alleviate and improve the symptoms to a certain extent, but can not heal completely. Therefore, it is very important to develop an effective method for the repairing of injured myocardium. This project aims to design and prepare injectable self-healing electroactive nanocomposite hydrogels for cardiac tissue engineering. First of all, electroactive materials will be synthesized with tetraaniline and aniline pentmer as the electroactive segments. Then the obtained electroactive materials will assemble into nanomicelles. These hydrazide nanomicells and four-armed PEG occour bio-orthogonal reaction with aldehyde dextran to form hydrazine bond cross-linked nanocomposite hydrogel with self-healing property. Furthermore, the nanomicells with hydrophobic core are easy to load hydrophobic small molecule drugs, so the gained electroactive nanocomposite hydrogels can easily achieve the co-delivery of drugs and bioactive factors. The synergistic effect of electroactive, small molecule drugs and bioactive factors on cardial tissue repair will be studied. The self-healing electroactive nanocomposite hydrogel may be used as a promising injectable biomaterial for cardiac tissue engineering in the future.

心肌梗死常伴有大量的心肌细胞死亡，进而发展为心力衰竭，是严重威胁人类健康的死亡杀手之一。由于成年心肌细胞难以再生，而传统的临床治疗措施只能在一定程度上缓解及改善症状，却无法根治。因此，发展一种有效的组织工程方法用于损伤心肌组织修复将具有十分重要的基础及临床研究意义。本项目以制备可注射、自修复电活性纳米复合凝胶为出发点，首先制备F127与苯胺低聚体共聚物材料并形成稳定分散的电活性纳米胶束；进一步，通过在电活性纳米胶束末端引入酰肼键，使其能够与醛基化的葡聚糖在水溶液中通过生物正交反应原位形成含腙键的自修复电活性纳米复合水凝胶。同时，将具有促进心肌修复和血管再生的小分子药物以及生物活性因子分别担载在电活性水凝胶疏水内核以及凝胶亲水基质中，实现小分子药物与生物活性因子的共担载，探索研究电活性、小分子药物和生物活性因子的协同作用对受损心肌修复的影响，从而为心肌组织再生修复提供一种新的思路和有益参考。

心肌梗死常伴有大量的心肌细胞死亡，进而发展为心力衰竭，已成为严重威胁人类健康的死亡杀手之一。由于成年心肌细胞难以再生，目前传统的临床治疗措施，只能在一定程度上缓解及改善症状，却无法根治。因此，发展一种有效的组织工程方法用于损伤心肌组织修复将具有十分重要的基础及临床研究意义。本项目以制备可注射、自修复、电活性纳米复合凝胶为出发点，首先采用含苯胺四聚体的葡聚糖、F127、四臂PEG等材料，通过腙键、肟键、可逆C=C双键等几种动态化学键交联，制备一系列可注射自修复的电活性水凝胶材料。通过考察电刺激下细胞在水凝胶里的增殖情况，研究水凝胶的力学性能和自修复性能，通过细胞和初步动物实验，探索水凝胶在细胞培养、伤口敷料、组织工程等生物领域的潜在应用，从而为心肌组织再生修复提供一种新的思路和有益参考。