Development of a Novel Composite Surgical Mesh

描述(由申请人提供)：以前的研究表明，1-6%的植入式医疗设备会被感染，1占医院感染的~45%2.在腹壁疝修补术中，感染发生的几率为2-10%(即开腹手术的感染率为7-18%，腹股沟手术的感染率为0-2%)3.疝修补术是世界各地普通外科医生最常进行的手术之一，美国每年进行超过100万次腹壁修补。其中，77万次是腹股沟修补4-6次。鉴于腹股沟和腹股沟疝的流行病学意义，确定一种合适而有效的疝修补术是非常重要的。现有的证据有力地支持在大多数患者中常规使用假体加强(网片)修补腹股沟。与人工网眼相关的三个主要难题是：1)容易导致慢性炎症和过度纤维化，导致网眼柔韧性丧失和植入部位僵硬增加；2)网眼植入后感染；3)聚酯网眼材料的降解。在本申请中，我们建议开发一种新型的复合外科网片，该复合手术网片基于具有插层硅橡胶涂层的PET网片，该涂层可以被配方为包括一种或多种活性药物，以：1)提高网片的生物相容性和生物稳定性，2)引导组织修复，以及3)降低设备对细菌定植、生物膜形成和感染的敏感性。具体来说，我们提出了以下目标：目的1.制备一种由PET基材和紫外光固化有机硅封装涂层组成的无药复合网状物，通过迭代提高涂层的均匀性和完整性来优化复合材料的制备参数，并在皮下植入模型中评价优化后的复合材料的体内性能。目的2.制备两种含两种活性药物成分抗菌剂的复合网状结构和两种由两种二元抗菌剂组成的复合网状结构，并对其体外性能(细菌学、药物释放、生物相容性等)进行表征。目的3.评估AIM开发的新型复合手术网的体外性能。作为这项拟议研究的结果，我们将开发一种新型复合手术网，其配方将包括一种或多种原料药，以：1)增强网眼的生物相容性和生物稳定性，2)减少炎症和纤维化，和/或3)降低器械对细菌定植、生物膜形成和感染的易感性。 公共卫生相关性：疝修补术是最常见的手术之一，常规使用假体加固(网片)修复疝气。与网眼相关的主要难题是它们容易引起炎症、纤维化、网眼植入后感染和聚酯网眼材料的降解。这项建议的目标是开发一种新型的复合手术网，其配方是为了提高生物相容性和生物稳定性，减少炎症，降低对细菌定植和生物膜形成的敏感性。

DESCRIPTION (provided by applicant): Previous studies have demonstrated that 1-6% of implanted medical devices become infected, 1 and account for ~45% of nosocomial infections 2. In ventral hernia repair, infections occur in 2-10 % of the time (i.e. open surgery 7-18% and laparoscopic 0-2% infection rates) 3. Hernia repairs are among the most commonly performed operations by general surgeons throughout the world with over 1 million abdominal wall repairs performed each year in the U.S. Of these, 770,000 are inguinal repairs 4-6. Given the epidemiologic significance of inguinal and ventral hernias, determining an appropriate and effective means of hernia repair is very important. The existing evidence strongly supports routine use of prosthetic reinforcement (meshes) for the repair of hernias in most patients. Three of the major dilemmas associated with prosthetic meshes are 1) their propensity to induce chronic inflammation and excessive fibrosis, with resulting loss of mesh pliability and increased stiffness at the site of the implantation, 2) post mesh implantation infections, and 3) degradation of the mesh material in the case of polyester. In the present application we propose to develop a new class of composite surgical meshes based on a PET mesh substrate with intercalating silicone elastomer coatings that may be formulated to include one or more active pharmaceutical agents in order to: 1) enhance mesh biocompatibility and bio- stability, 2) guide tissue repair, and 3) decrease the susceptibility of the device to bacterial colonization, biofilm formation and infection. Specifically we propose to the following aims: Aim 1. Formulate a drug-free composite mesh comprising a PET substrate and a UV-curing silicone encapsulating coating, optimize the composite fabrication parameters by iteratively improving coating uniformity and integrity, and evaluate the in vivo performance of the optimized composite in a subcutaneous implant model. Aim 2. Fabricate two composite mesh configurations comprising two individual active pharmaceutical ingredient antimicrobial agents and two composite mesh configurations each comprising a binary antimicrobial agent system and characterize in vitro performance (bacteriology, drug delivery, biocompatibility index etc.) vs. dose, and choose the two optimal dose/concentration configurations for a detailed in vivo evaluation in Aim 3. Aim 3. Evaluate the in vivo performance of the top two in vitro performing novel composite surgical meshes developed in Aim 2. As a result of this proposed research we will have developed a new class of composite surgical meshes based on a polyester mesh substrate with intercalating silicone elastomer coatings that may be formulated to include one or more APIs in order to: 1) enhance mesh biocompatibility and bio-stability of the mesh, 2) decrease inflammation and fibrosis, and/or 3) decrease the susceptibility of the device to bacterial colonization, biofilm formation and infection. PUBLIC HEALTH RELEVANCE: Hernia repair is among the most commonly performed operations and routinely prosthetic reinforcement (meshes) is utilized for the repair of hernias. Major dilemmas associated with meshes are their propensity to induce inflammation; fibrosis, post mesh implantation infection and degradation of the polyester mesh material. The goal of this proposal is to develop a new class of composite surgical meshes, which are formulated to enhance biocompatibility and bio stability, decrease inflammation and decrease susceptibility to bacterial colonization and biofilm formation.