Reducing Adhesions in Hernia Repair Meshes Through a Polysaccharide Coating

抽象概括 虽然所有植入物都有产生术后粘连的能力， 粘连率高达58%，这是如此令人望而却步，需要进一步干预。古典 使用聚合物网或网涂层的方法尚未被普遍采用 成本，不良的网状结构，或免疫激活和进一步放大慢性炎症的能力， 炎症抗粘附表面如内皮糖萼是由细胞表面寡聚体形成的。 和多糖，其易于复制且无免疫原性。因此，我们建议 创建一个多糖基聚合物家族，用于涂覆疝修补补片， 糖萼的粘附特性。在体外以及啮齿动物和猪模型中的初步数据 显示该策略可减少超出无涂层补片的粘连。我们的长期目标是 开发一种低成本、生物相容性的器械涂层，可以防止或减少术后粘连。 本提案的目的是评估能够防止 粘连，同时保持补片修复耐久性和生物相容性。核心假设是， 基于多糖的聚合物，由于其形成水壳的能力，将抵抗蛋白质吸附 和细胞粘附，减少术后粘连的数量。这项工作将在 三个目的：1）增强防止蛋白质和细胞粘附在疝补片上的能力。2)评价 涂层对疝修补术术后粘连和耐久性影响。3)检查生物相容性 在我们的啮齿类动物模型中的聚合物涂层。我们提出的工作是创新的，它模仿简单的糖 减少粘连的化学物质;并且通过使用天然来源的分子， 生物相容性预期成果包括平台技术，广泛适用于 减少术后粘连。这些结果将对普通外科领域产生积极影响， 提供了一个解决方案，一个棘手的问题，复杂的外科护理，因为网格被引入 差不多50年前。未来的工作将在分子水平上进一步评估生物相容性，并转化为 疝修补术和术后粘连的大型动物模型。

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.