具有主动释放一氧化氮、抗感染和促进组织愈合的新型复合生物补片的研究

Acellular biological grafts is an important development of hernia surgery and abdominal wall repair material, but the resistance to infectious deficiencies existing products, and use of acellular biological grafts for abdominal hernia repair can result in significant laxity(diastasis) and even hernia recurrence after long-term follow-up, which limits its application scope. Our pilot study has been selected a suitable biological graft for repair of abdominal wall defects and confirmed that fill in embedded nanoparticles in biological grafts enhance anti infective feasibility. Our relevant work has applied four national invention patents (one published online) and our previous works have been published in the world ranked first in the field of surgery and materials journal Ann Surg and Biomaterials. This topic aiming at the shortcomings of the prophase work found in plans to further improve, carry out (1) assembly can release nitric oxide nanoparticles can be absorbed and by using electrochemical deposition self-assembly technology, biological patch, by means of the nitric oxide release rate of resistance to infection, accelerate tissue healing; (2) build biological - polymer composite patch "sandwich", in order to make sure the repaired area with low levels of permanent implants of synthetic fiber and collagen ("reinforced concrete") stable structure, prevent bulging, reduce shrinkage or extension; (3) by in vitro and in vivo tests,to make sure the new design material properties and biological safety in order to suitable for clinical use. Expected results in the present works will help us to expand scientific and effective application of biological grafts in surgery.

生物补片是疝和腹壁外科修复材料的重要发展，但现有产品存在抗感染性不足、远期易膨出等缺陷，限制了应用。我们前期已筛选出适合于腹壁修复的植入纳米颗粒猪小肠粘膜下层，并证实纳米技术修饰生物补片提升抗感染性的思路可行，相关工作已获国家发明专利、实用新型专利（共4项，含公示1项），并以论著分别发表于世界外科学和材料学排名第1杂志Ann Surg和Biomaterials。本项目针对前期工作中发现的不足拟进一步改进，开展①组装能主动释放一氧化氮的可吸收纳米微粒，并利用电化学沉积自组装技术植入生物补片，通过一氧化氮的不同释放速度实现抗感染、加速组织愈合等特性；②构建生物－高分子"三明治"复合补片，以保证修复区远期有低量永久性植入物，形成合成纤维-胶原（"钢筋-混凝土"）稳定结构，预防膨出，减少皱缩或延伸；③体外、内全方位检测材料性能和生物安全性，以适合应用。预期结果有助于拓展生物补片科学、有效地应用。

生物补片是疝和腹壁外科修复材料的重要发展方向，但临床现有产品存在抗感染性不足、修复区远期易膨出等缺陷，限制其应用范围。本课题基于筛选出的适合于腹壁修复的生物补片组织来源等前期工作，进一步完成①新型缓释抗菌生物补片的构建，体内外试验证实其具备高效、广谱、持久的主动抗菌性，组织相容性良好并促组织愈合，符合伴有污染或感染腹壁缺损修复重建需要。②抗菌生物-高分子“三明治”复合补片的构建，体内外试验证实其能有效弥补单纯生物补片修复区远期易发生腹壁膨出的不足，确认增加高分子合成纤维并未降低抗感染生物补片预防创面感染的有效性。③抗菌复合补片的生物安全性检测，证实其安全、有效，符合临床应用需求。本课题研究成果已在材料学顶级期刊《Biomaterials》（IF 8.557）上发表论著1篇和方法学论著1篇，另发表中文核心期刊综述2篇，尚有SCI高分值论文1篇修回中。授权国家发明专利1项。参加多次国内学术会议交流，项目组负责人和成员分别获批国家863计划1项、国家自然科学基金面上项目1项、青年项目1项，培养博士生2名、硕士生1名。研究成果有助于促进生物补片未来大规模的有效应用。