Development of a Novel Composite Surgical Mesh

新型复合手术网片的开发

• 批准号: 8394384
• 负责人: DON KREUTZER
• 金额: $ 34.53万
• 依托单位: CELL/MOLECULAR TISSUE ENGINEERING LLC
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-14 至 2015-09-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8394384
• 关键词: Accounting; Animal Model; Area; Bacteriology; Blood; Catheters; Characteristics; Chlorhexidine; Chronic; Collaborations; Collagen; Collagen Fiber; Development; Devices; Dose; Drug Delivery Systems; Encapsulated; Epidemiology; Evaluation; Fiber; Fibrosis; Foreign Bodies; Foreign-Body Reaction; Future; Giant Cells; Goals; Grant; Healed; Hernia; Implant; In Vitro; Individual; Infection; Inflammation; Inguinal Hernia; Inguinal region; Length of Stay; Life; Mechanics; Medical Device; Microbial Biofilms; Minocycline; Modeling; Morbidity - disease rate; Nosocomial Infections; Operative Surgical Procedures; Outcome; Pain; Patients; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Pliability; Polyesters; Polyethylene Terephthalates; Polypropylenes; Postoperative Period; Predisposition; Prevention; Process; Prosthesis; Psychological reinforcement; Reconstructive Surgical Procedures; Recovery; Research; Rifampin; Silicone Elastomers; Silicones; Silver; Site; Stream; Structure; Sulfadiazine; Surface; Surgeon; Surgical Mesh; System; Time; Tissues; Trichrome stain; Ventral Hernia; abdominal wall; antimicrobial drug; base; biomaterial compatibility; calcification; chronic pain; cost; design; functional loss; healing; implantation; improved; in vivo; indexing; mortality; novel; operation; phase 1 study; repaired; response; subcutaneous; tissue repair; vessel regression

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.

描述（由申请人提供）：之前的研究表明，1-6% 的植入医疗器械会被感染，1 约占院内感染的 45% 2。在腹疝修补术中，感染发生的概率为 2-10% （即开腹手术感染率为 7-18%，腹腔镜手术感染率为 0-2%） 3. 疝修补术是全世界普通外科医生最常进行的手术之一，手术人数超过 100 万例美国每年进行腹壁修复术，其中 770,000 例是腹股沟修复术 4-6。鉴于腹股沟疝和腹疝的流行病学意义，确定适当且有效的疝修补方法非常重要。现有证据强烈支持大多数患者常规使用假体加固（网片）来修复疝气。与假体网片相关的三个主要困境是：1）它们容易诱发慢性炎症和过度纤维化，从而导致网片柔韧性丧失和植入部位的刚度增加，2）网片植入后感染，以及3）如果是聚酯，则为网状材料。在本申请中，我们建议开发一类新型复合手术网片，其基于具有插入有机硅弹性体涂层的PET网片基底，其可配制为包含一种或多种活性药剂，以便：1)增强网片的生物相容性和生物相容性。稳定性，2) 引导组织修复，3) 降低装置对细菌定植、生物膜形成和感染的敏感性。具体来说，我们提出以下目标： 目标 1. 配制由 PET 基材和紫外固化有机硅封装涂层组成的无药复合网，通过迭代提高涂层均匀性和完整性来优化复合材料制造参数，并评估体内性能皮下植入模型中优化复合材料的研究。目标 2. 制造两种复合网状结构，包括两种单独的活性药物成分抗菌剂和两种复合网状结构，每种结构均包括二元抗菌剂系统，并表征体外性能（细菌学、药物递送、生物相容性指数等）与剂量的关系，并选择目标 3 中详细体内评估的两种最佳剂量/浓度配置。 目标 3. 评估目标 2 中开发的前两种体外性能新型复合手术网片的体内性能。研究中，我们将开发一种新型复合手术网片，其基于聚酯网片基材，并具有插入的有机硅弹性体涂层，其配方可包含一种或多种 API，以便：1）增强网片的生物相容性和生物稳定性， 2)减少炎症和纤维化，和/或3)降低装置对细菌定植、生物膜形成和感染的敏感性。 公众健康相关性：疝气修复是最常进行的手术之一，并且常规使用假体加固（网片）来修复疝气。与网格相关的主要难题是它们容易诱发炎症；纤维化、网片植入后感染和聚酯网片材料的降解。该提案的目标是开发一类新型复合手术网片，其配方旨在增强生物相容性和生物稳定性，减少炎症并降低对细菌定植和生物膜形成的敏感性。