Houston Methodist Research Institute, Houston, Texas, USA.
Department of Surgery, Section of Colon and Rectal Surgery UT Health Science Center at Houston, McGovern Medical School, Houston, Texas, USA.
Surg Infect (Larchmt). 2021 Nov;22(9):910-922. doi: 10.1089/sur.2020.288. Epub 2021 Apr 30.
Infected hernia mesh is a cause of post-operative morbidity. Nitric oxide (NO) plays a key role in the endogenous immune response to infection. We sought to study the efficacy of a NO-releasing mesh against methicillin-resistant (MRSA). We hypothesized that a NO-releasing polyester mesh would decrease MRSA colonization and proliferation. A composite polyester mesh functionalized with -diazeniumdiolate silica nanoparticles was synthesized and characterized. -diazeniumdiolate silica parietex composite (NOSi) was inoculated with 10,10, or 10 colony forming units (CFUs) of MRSA and a dose response was quantified in a soy tryptic broth assay. Utilizing a rat model of contaminated hernia repair, implanted mesh was inoculated with MRSA, recovered, and CFUs were quantified. Clinical metrics of erythema, mesh contracture, and adhesion severity were then characterized. Methicillin-resistant CFUs demonstrated a dose-dependent response to NOSi in vitro. In vivo, quantified CFUs showed a dose-dependent response to NOSi-PCO. Treated rats had fewer severe adhesions, less erythema, and reduced mesh contracture. We demonstrate the efficacy of a NO-releasing mesh to treat MRSA in vitro and in vivo. Creation of a novel class of antimicrobial prosthetics offers new strategies for reconstructing contaminated abdominal wall defects and other procedures that benefit from deploying synthetic prostheses in contaminated environments.
感染性疝补片是术后发病率的一个原因。一氧化氮(NO)在感染的内源性免疫反应中起着关键作用。我们试图研究释放 NO 的补片对耐甲氧西林金黄色葡萄球菌(MRSA)的疗效。我们假设释放 NO 的聚酯补片会减少 MRSA 的定植和增殖。合成了一种用-二氮烯二酸盐硅纳米粒子功能化的复合聚酯补片,并对其进行了表征。用-二氮烯二酸盐硅纳米粒子复合(NOSi)接种 10、10 或 10 个 CFU 的 MRSA,并在大豆胰蛋白酶肉汤测定中定量测定剂量反应。利用污染疝修复的大鼠模型,将植入的补片接种 MRSA,回收并定量 CFU。然后对红斑、补片挛缩和粘连严重程度的临床指标进行了表征。耐甲氧西林金黄色葡萄球菌的 CFU 在体外对 NOSi 表现出剂量依赖性反应。在体内,定量 CFU 显示出对 NOSi-PCO 的剂量依赖性反应。治疗组大鼠的严重粘连较少,红斑较轻,补片挛缩减少。我们证明了释放 NO 的补片在体外和体内治疗 MRSA 的疗效。新型抗菌假体的创建为重建污染的腹壁缺损和其他受益于在污染环境中部署合成假体的手术提供了新的策略。