基于脱细胞真皮基质的抗感染复合组装生物-合成材料在严重腹腔感染中的实验研究

Temporary abdominal closure techniques are widely involved in the treatment of severe abdominal infection and other critically ill patients whose abdominal cavities need to be opened. Our previous work demonstrated that although synthetic mesh could protect the bowel and decrease abdominal decompression in open abdominal therapy, complications such as mesh infection, adhesion, bowel obstruction, fistula and others still occur sometimes. Application of existing biological materials could solve the problem in a bio-compatibility way. However, shortcomings such as lack of resistance to infection, bulging easily after a long-term and abdominal wall hernia defects limit the application. We speculate that the outcome of patients who received open abdomen therapy in the treatment of abdominal infection would be largely improved if the biological materials are composites with a high molecular lightweight polypropylene with anti-infective nano silver particles in the ultra-structure of their three-dimensional network. In this study, we aimed to invent a self-assembly, nano-silver- biological collagen - synthetic fiber material which derived from an acellular dermal matrix with low enzymatic antigenicity and high content of collagen fitted by thermochemical light-weight polypropylene, as the "reinforced - concrete" material. Animal study, which conducted in abdominal infection model would investigate the mechanism of neovascularization and host cell ingrowth to ensure effective long-term repair area and of low levels of permanent implants. The clinical study is expected to provide new theoretical and experimental basis for the treatment of severe abdominal infection and temporary abdominal closure technology in open abdominal therapy.

严重腹腔感染等危重症的救治经常需要行腹腔开放治疗并应用临时关腹技术。我们前期工作发现，应用合成网片虽然实现了保护肠管、腹腔减压的作用，但网片感染、肠粘连、梗阻甚至肠瘘等并发症时有发生。现有生物材料的应用解决了生物相容性问题，但是存在抗感染性不足、远期易膨出甚至腹壁疝等缺陷，限制了应用。我们推测，如果将生物材料与高分子轻量型聚丙烯复合组装，并在其三维网状超微结构内植入具有抗感染性的纳米银微粒，将显著改善严重腹腔感染后腹腔开放的治疗效果。本研究拟通过酶法制备抗原性低、胶原含量高的脱细胞真皮基质，并与轻量型聚丙烯进行热化学嵌合；通过自组装技术构建纳米银-生物胶原-合成纤维的"钢筋-混凝土"材料，并结合严重腹腔感染的腹腔开放动物模型，研究其促进新生血管和宿主细胞长入，并保证修复区远期有低量永久性植入物的效果与机制。研究结果可望为临床严重腹腔感染实施腹腔开放及临时关腹技术提供新的理论基础和实验依据。

严重腹腔感染等危重症的救治经常需要行腹腔开放治疗并应用临时关腹技术。我们发现，应用合成补片虽然实现了保护肠管、腹腔减压的作用，但补片感染、肠粘连、肠梗阻甚至肠瘘等并发症仍时有发生。现有生物补片的应用解决了生物相容性问题，但由于早期缺乏新生血管长入，补片周围不能增殖形成牢固的组织包裹，随着生物补片的逐步降解常常导致远期膨出甚至腹壁疝等缺陷，限制了应用。我们推测，如果将载有血管活性物质的微球型药物递送系统（Microparticle-based drug delivery system，MDDS）和生物补片组装成复合补片，将能够显著改善严重腹腔感染后腹腔开放的治疗效果。.本研究通过构建毛细管微流控芯片，分别制备：（1）丝素蛋白（silk fibroin，SF）包裹中空介孔二氧化硅纳米粒子（hollow mesoporous silica nanoparticles，HMSNs）的复合微球（composite microparticles，CMs）；（2） 包裹有HMSNs的聚（乳酸-羟基乙酸共聚物）（poly(lactic-co-glycolic acid)，PLGA）多孔微球（HMSNs/PLGA porous microparticles，HPMs）；（3）聚(N-异丙基丙烯酰胺)（poly(N-isopropylacrylamide)，PNIPAM）和甲基丙烯酸酯化明胶（methacrylate gelatin，GelMA）包裹氧化石墨烯（graphene oxide，GO）的光响应性微球（photoresponsive delivery microcarriers，PDMs）。.制备的3种微球具有各自独特的结构和功能。（1）CMs具有特殊的微纳结构，有效避免了药物的突释，并通过改变HMSNs的浓度，调控药物的释放速率。（2）HPMs具有精确可调的开口结构，可以缓慢、持续地释放药物，且随着微球表面开口结构的增加，药物的释放速率加快。（3）PDMs具有稳定、可重复的近红外（near-infrared，NIR）光响应性，随着NIR光刺激频次的增加，药物从PDMs的释放速率加快。这3种MDDS分别与生物补片组装成复合补片后，都能够在大鼠体内促进新生血管的形成，改善严重腹腔感染后腹腔开放的治疗效果。研究结果为临床严重腹腔感染实施腹腔开放及临时关腹技术提供新的理论基础。