Engineering a naturally derived and highly adhesive surgical sealant

设计一种天然衍生的高粘合性手术密封剂

• 批准号: 9920717
• 负责人: Nasim Annabi
• 金额: $ 62.95万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9920717
• 关键词: Address; Adhesions; Adhesives; Air; Anastomosis - action; Animal Model; Binding; Biocompatible Materials; Biopolymers; Blood Vessels; Body Fluids; Cardiovascular Surgical Procedures; Catechols; Characteristics; Chemicals; Clinic; Clinical; Consumption; Cyanoacrylates; Data; Defect; Development; Devices; Engineering; Environment; Exhibits; Extravasation; Family suidae; Fibrin Tissue Adhesive; Formulation; Gelatin; Goals; Hydrogels; In Vitro; Infection; Ischemia; Light; Liquid substance; Liver; Lung; Mechanics; Methods; Modeling; Movement; Mussels; Operative Surgical Procedures; Outcome; Pleural; Polymers; Postoperative Period; Procedures; Property; Punch Biopsy; Rattus; Site; Solid; Structure; Structure of parenchyma of lung; Surface; Surgeon; Surgical Mesh; Surgical complication; Surgical sutures; Testing; Thoracic Surgical Procedures; Time; Tissues; Toxic effect; Visible Radiation; Work; base; biomaterial compatibility; chemical bond; cost; crosslink; design; flexibility; implantation; improved; in vivo; in vivo evaluation; injured; mechanical properties; minimally invasive; novel; physical property; pressure; prevent; repaired; seal; skills; soft tissue; subcutaneous; surgery material; wound; wound closure

Contact PD/PI: Annabi, Nasim Project Summary/Abstract Approximately 114 million surgical and procedure-based wounds occur annually worldwide, including 36 million from surgery in the U.S. Damages to delicate soft tissues, such as lung, liver, land blood vessels, are particularly challenging to repair. When these tissues are punched for biopsy or injured during procedures, they must be reconnected surgically using sutures, staples, or implantation of surgical meshes. Despite their common use in clinics, these mechanical methods are associated with inevitable tissue damages caused by deep piercing and ischemia. These methods are also time-consuming, demand surgeon's skills during the surgeries, and might cause post-surgical complications such as infection. To resolve these issues, various types of surgical materials have been used for sealing, reconnecting tissues, or attaching devices to tissues. Despite the emergence of several surgical sealants, the biomaterials used as sealants/adhesives often have some drawbacks that limit their applications, such as low mechanical properties, toxicity effects or toxic degradation products, and poor adhesive strength; therefore none of them meet all the necessary needs to replace sutures and staples. An ideal surgical sealant is required to be flexible to be able to adapt with dynamic movement of native tissues, have excellent biocompatibility and controlled biodegradability, and provide high adhesive strength and burst pressure particularly in the presence of body fluids. In this proposal, we aim to engineer a novel and highly adhesive surgical sealant with tunable adhesion strength from a light-activated naturally derived hydrogel, gelatin methacryloyl (GelMA), for surgical applications (e.g. lung surgery). We will chemically modify the engineered GelMA hydrogels with catechol to form gelatin methacryloyl-catechol (GelMAC) with enhanced adhesion to the native tissues. We will then evaluate the function of the engineered surgical material as a lung sealant in both small and large animal models. Our preliminary data suggests that this material is superior to the existing products in the market and may generate a paradigm-shifting surgical material that may not require sutures due to its superior mechanical and adhesive properties. The engineered highly adhesive surgical sealant can be potentially used to stop air leakages after lung surgery and also support new tissue formation to repair the defected sites. Due to its high adhesion to the native tissues and biocompatibility, the engineered adhesives in this proposal have potential to be used in various procedures such as anastomoses, cardiovascular surgeries, and wound closure. Project Summary/Abstract Page 7

联系人 PD/PI：Annabi、Nasim 项目概要/摘要 全球每年发生约 1.14 亿例外科手术伤口，其中 3600 万例 在美国进行的手术对肺、肝、陆地血管等脆弱软组织的损害尤其严重 修复具有挑战性。当这些组织被打孔进行活检或在手术过程中受伤时，必须将它们 使用缝合线、U形钉或植入手术网片通过手术重新连接。尽管它们普遍用于 在诊所中，这些机械方法不可避免地会因深刺和穿刺而造成组织损伤。 缺血。这些方法也很耗时，对手术过程中外科医生的技能要求很高，并且可能会影响手术效果。 引起感染等术后并发症。为了解决这些问题，各种类型的手术材料 已用于密封、重新连接组织或将装置连接至组织。尽管出现了 与几种手术密封剂相比，用作密封剂/粘合剂的生物材料通常具有一些限制 它们的应用，例如低机械性能、毒性作用或有毒降解产物，以及较差的 粘合强度；因此，它们都无法满足替代缝线和U形钉的所有必要需求。一个理想 手术密封剂需要具有灵活性，能够适应天然组织的动态运动， 优异的生物相容性和可控的生物降解性，并提供高粘合强度和爆破压力 特别是在有体液存在的情况下。在这个提案中，我们的目标是设计一种新颖且高度粘合的 具有可调粘合强度的手术密封剂，由光激活的天然水凝胶、明胶制成 甲基丙烯酰 (GelMA)，用于外科手术（例如肺部手术）。我们将对工程进行化学修饰 GelMA 水凝胶与儿茶酚形成明胶甲基丙烯酰儿茶酚 (GelMAC)，具有增强的粘附力 天然组织。然后，我们将评估工程外科材料作为肺密封剂的功能 小型和大型动物模型。我们的初步数据表明，这种材料优于现有的 市场上的产品，可能会产生一种改变范式的手术材料，由于这种材料可能不需要缝合 其卓越的机械和粘合性能。工程设计的高粘合性手术密封剂可以 可能用于阻止肺部手术后漏气，也可以支持新组织的形成来修复 缺陷站点。由于其对天然组织的高粘附力和生物相容性，工程粘合剂 该提案有可能用于各种手术，例如吻合术、心血管手术、 和伤口闭合。 项目总结/摘要第 7 页