Reducing Adhesions in Hernia Repair Meshes Through a Polysaccharide Coating

通过多糖涂层减少疝气修复网的粘连

• 批准号: 9215133
• 负责人: Horst A. von Recum
• 金额: $ 29.07万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9215133
• 关键词: Acute; Address; Adhesions; Adhesives; Adonis; Adopted; Adsorption; Animal Model; Animals; Antibodies; Award; Biocompatible Materials; Biology; Biomechanics; Biomedical Engineering; Caring; Cell Adhesion; Cell surface; Cells; Characteristics; Chemistry; Chronic; Clinical; Collaborations; Data; Devices; Environment; Enzyme-Linked Immunosorbent Assay; Failure; Family; Family suidae; Future; Generations; Glycocalyx; Goals; Grant; Hernia; Histologic; Histology; Immune; Immune response; Implant; In Vitro; Incidence; Infection; Inflammation; Inflammatory; Intervention; Intestines; Investigation; Life; Mechanics; Methods; Microarray Analysis; Modeling; Molecular; Oligonucleotides; Operative Surgical Procedures; Outcome; Pain; Patients; Pelvic floor structure; Polyethylene Glycols; Polymers; Polysaccharides; Population; Property; Prosthesis; Proteins; Public Health; Recording of previous events; Research Personnel; Resistance; Rodent; Rodent Model; Side; Small Business Innovation Research Grant; Study models; Surface; Surgeon; System; Technology; Tensile Strength; Testing; Tissues; Translating; Translations; United States National Institutes of Health; Universities; Vagina; Ventral Hernia; Water; Work; abdominal wall; base; biocompatible polymer; biomaterial compatibility; cost; crosslink; density; immune activation; in vivo; innovation; migration; non-Native; prevent; repaired; success

Abstract Summary While all implants have capacity for generation of post-surgical adhesions, there is an estimated incidence rate as high a 58%, of adhesions which are so prohibitive that further intervention is warranted. Classical approaches of using polymer meshes or mesh coatings have not been universally adopted due to high cost, poor mesh mechanics, or capacity for immune activation and further amplification of chronic inflammation. Anti-adhesive surfaces such as the endothelial glycocalyx are formed by cell surface oligo- and polysaccharides, which are simple to reproduce and non-immunogenic. Therefore, we propose to create a family of polysaccharide-based polymers to coat hernia repair meshes mimicking the anti- adhesive properties of the glycocalyx. Preliminary data both in vitro and in rodent and pig models have shown this strategy to reduce adhesions beyond that of uncoated meshes. Our long-term goal is to develop a low-cost, biocompatible device coating which can prevent or reduce post-surgical adhesions. The objective of this proposal is to assess the range of polysaccharide chemistries capable of preventing adhesions, while retaining mesh repair durability and biocompatibility. The central hypothesis is that polysaccharide-based polymers, due to their capacity to form a water shell will resist protein adsorption and cell adhesion, reducing the number of post-surgical adhesions. This work will be accomplished in three aims: 1) Validate the capacity to prevent protein and cell adhesion on hernia meshes. 2) Evaluate impact of coating on post-surgical adhesion and durability of hernia repair. 3) Examine biocompatibility of polymer coatings in our rodent model. Our proposed work is innovative; it mimics simple saccharide chemistries to reduce adhesions; and by using naturally-derived molecules has a higher likelihood of biocompatibility. The expected outcomes include a platform technology, broadly applicable for use in reducing post-surgical adhesions. These results will positively impact the field of general surgery by providing a solution to a vexing problem that has complicated surgical care since meshes were introduced nearly 50 years ago. Future work will further assess biocompatibility at a molecular level, and translate to a large animal model of hernia repair and post-surgical adhesion.

摘要摘要 虽然所有植入物具有产生后手术后粘附的能力，但估计发病率 速率是高达58％的粘附，这些粘连是如此高的粘连，以至于需要进一步干预。古典 使用聚合物网格或网格涂层的方法尚未普遍采用 成本，较差的网格力学或免疫激活的能力和进一步扩增慢性 炎。细胞表面寡核形成抗粘附性表面，例如内皮糖囊肿 和多糖，易于繁殖和非免疫原性。因此，我们建议 创建一个基于多糖的聚合物家族，以涂上疝气修复的覆盖，以模仿抗 糖蛋白的粘附特性。初步数据在体外和啮齿动物和猪模型中都具有 显示了这种策略，以减少超出未涂层网格的粘附。我们的长期目标是 开发低比较生物相容性的设备涂料，该涂层可以预防或减少手术后粘连。 该提案的目的是评估能够防止的多糖化学的范围 粘连，同时保留网格修复耐用性和生物相容性。中心假设是 多糖基聚合物由于它们形成水壳的能力将抵抗蛋白质吸附 和细胞粘附，减少后手术后粘连的数量。这项工作将完成 三个目的：1）验证防止疝网蛋白和细胞粘附的能力。 2）评估 涂层对疝修复后手术后粘附和耐用性的影响。 3）检查的生物相容性 我们的啮齿动物模型中的聚合物涂料。我们提出的工作是创新的。它模仿简单的糖糖 化学以减少粘附；通过使用自然衍生的分子具有更高的可能性 生物相容性。预期的结果包括一种平台技术，广泛适用于 减少手术后粘附。这些结果将通过 由于引入了网格 大约50年前。未来的工作将进一步评估分子水平的生物相容性，并转化为 大疝修复和手术后粘附的大动物模型。