功能化金属有机供骨架强化自动适应性水凝胶在腹腔开放创面早期保护中的应用基础研究

Open abdomen is an important clinically therapy for severe abdominal trauma, severe abdominal infection and intra-abdominal hypertension, and can reduce intra-abdominal pressure, control abdominal infections and timely discover and deal with intra-abdominal viscera injury. However, the opened abdomen faces the risk of exposed bowel injury and enteroatmospheric fistula formation, which will seriously affect the therapeutic effect and threaten the patient's life. The present temporary closure materials have poor biocompatibility, poor permeability, non-degradable and non-antibacterial properties, so can’t offer effective protection. The structure of bioinspired hydrogel is similar with the extracellular matrix, possessing good-security, biocompatibility, permeability, and biodegradation capabilities. Among all kinds of inspired hydrogels, the self-healing hydrogel shows particularly prominent performance, can recover its original structure and functions after injury and automatically adapt to the wound surface, filling the gap of the wound. In this study, we synthesis the wound-adapting, self-healing through the reaction between dodecyl-modified chitosan and benzaldehyde-terminated polyethylene glycol, and bring in the functional metal organic frameworks which are made from copper and niacin to enhance the mechanical strength, anti-infection and promoting wound healing capabilities of the hydrogel. We aim at developing functional metal organic frameworks reinforced automatic adaptive hydrogel to solve the problem of early open abdomen wound protection.

腹腔开放疗法是临床上救治严重腹部创伤、重度腹腔感染以及腹腔高压的重要治疗手段，可以降低腹内压、控制腹腔感染、及时发现并处理腹腔内脏器损伤。但是开放的腹腔面临着裸露肠管损伤，出现肠空气瘘的风险，严重影响治疗效果并威胁病人生命。现有的临时关腹材料生物相容性差、透气性差、不可降解、无抗菌性能，无法可以起到有效的保护作用。而生物响应性水凝胶结构与细胞外基质十分类似，具有良好的安全性、生物相容性、透气性、可降解性，其中，自修复水凝胶性能尤为突出，在损伤后仍可恢复材料原有结构和功能，而且可以自动适应创面表面，填充创面间隙。本研究拟通过烷烃化壳聚糖与聚乙二醇苯甲醛反应成自动适应性自修复水凝胶，并利用铜离子和烟酸自主合成功能化金属有机骨架引入水凝胶体系，对其机械性能、抗菌性能、促修复等方面进行强化，制备功能化金属有机骨架强化自动适应性水凝胶，并探索其促进创面愈合的机制，有望解决腹腔开放创面早期保护的难题。

腹腔开放疗法是临床上救治严重腹部创伤、重症腹腔感染以及腹腔高压等外科危重症的重要治疗手段，但是开放的腹腔面临着裸露肠管损伤，出现肠空气瘘的风险，严重影响治疗效果并威胁生命，死亡率高达4.5%-41.2%。现有的临时关腹材料生物相容性差、透气性差、不可降解、无抗菌性能，无法可以起到有效的保护作用。因此研发新型材料有效保护腹腔开放创面、减少肠管损伤、促进组织修复从而避免肠空气瘘的发生具有重要的临床意义。.课题组先后研制了包括金属有机骨架水凝胶、凝胶-纳米纤维支架复合材料、微凝胶组装体、创面流体定向渗透材料和基于多巴胺修饰的透明质酸合成的多功能水凝胶等多种新型材料，逐步实现了腹腔开放创面保护材料的生物相容性好、透气性佳、可降解、抗菌、抗氧化、促修复、微环境调节、渗液定向渗透等性能，为腹腔开放创面保护提供了新型材料学支持。相关研究成果分别发表于《Advanced Materials》、《Advanced Science》、《Nanomaterials》、《Int J Biol Macromol》、《J Biomed Nanotechnol》、《Research》、《J Colloid Interface Sci》等杂志。项目负责人作为第四完成人获2020年江苏省科学技术奖一等奖：《外科感染防治的进步》。