Engineering a naturally derived and highly adhesive surgical sealant

联系PD/PI：Annabi，Nasim 项目摘要/摘要 全世界每年约发生1.14亿例手术和手术创伤，其中3600万例 在美国，手术对脆弱的软组织，如肺、肝、陆地血管的损害尤其严重。 修理起来很有挑战性。当这些组织被穿孔进行活组织检查或在手术中受伤时，它们必须 通过手术缝合、缝合或植入外科网状物重新连接。尽管它们在 临床上，这些机械方法与深穿孔和直视手术不可避免的组织损伤有关 缺血症。这些方法也很耗时，在手术过程中需要外科医生的技能，而且可能 导致手术后并发症，如感染。为了解决这些问题，各种类型的手术材料 已被用于密封、重新连接组织或将设备连接到组织。尽管出现了 几种外科密封剂，用作密封剂/粘合剂的生物材料往往存在一些缺陷，限制了 它们的应用，如机械性能低，毒性作用或有毒降解产物，且较差 粘合强度；因此，它们都不能满足更换缝合线和订书机的所有必要需求。一种理想 手术封闭剂要求具有柔韧性，能够适应自然组织的动态运动，具有 良好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 尤其是在有体液的情况下。在这项提案中，我们的目标是设计一种新型的高度粘合的 由光激活的天然水凝胶明胶制成的粘接强度可调的外科密封胶 甲基丙烯酰(GelMA)，用于外科手术(如肺部手术)。我们将对经过化学改造的 GelMA水凝胶与邻苯二酚形成明胶-甲基丙烯酰基-邻苯二酚(GelMAC)，可增强与 原生组织。然后，我们将评估工程外科材料作为肺密封剂在两种情况下的功能 小动物模型和大动物模型。我们的初步数据表明，这种材料优于现有的 市场上的产品，并可能产生一种改变范式的手术材料，可能不需要缝合 其优异的机械和粘合性能。设计的高度粘合的外科密封胶可以 潜在地用于阻止肺部手术后的空气泄漏，并支持新组织的形成以修复 叛逃地点。由于其对天然组织的高度粘附性和生物相容性，在 这一建议有可能用于各种手术，如吻合术，心血管手术， 伤口闭合。 项目摘要/摘要第7页

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