Engineering a naturally derived and highly adhesive surgical sealant

联系PD/PI：Annabi、Nasim 项目总结/摘要 全世界每年发生约1.14亿例手术和基于程序的伤口，其中包括3600万例 对脆弱的软组织，如肺、肝、陆地血管的损伤， 修复的挑战。当这些组织被穿刺进行活检或在手术过程中受伤时，它们必须 使用缝合线、斯台普斯或植入外科补片通过外科手术重新连接。尽管它们的常见用途是 在临床上，这些机械方法与由深穿刺引起的不可避免的组织损伤相关， 缺血这些方法也是耗时的，需要外科医生在手术期间的技能，并且可能 引起感染等术后并发症。为了解决这些问题， 已经被用于密封、重新连接组织或将装置附着到组织上。尽管出现了 在几种外科密封剂中，用作密封剂/粘合剂的生物材料通常具有一些缺点， 它们的应用，例如低的机械性能、毒性作用或毒性降解产物，以及差 粘合强度;因此，它们都不能满足替代缝线和斯台普斯的所有必要需求。一个理想 外科密封剂需要是柔性的，以便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 特别是在体液存在的情况下。在这项提案中，我们的目标是设计一种新型的高粘性 来自光活化天然衍生水凝胶明胶的具有可调粘附强度的外科密封剂 甲基丙烯酰基（GelMA），用于外科应用（例如肺手术）。我们会用化学方法改变 GelMA水凝胶与邻苯二酚形成明胶甲基丙烯酰邻苯二酚（GelMAC），其具有增强的粘附性。 天然组织然后，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。 小型和大型动物模型。我们的初步数据表明该材料优于现有材料的上级 可能会产生一种范式转变的外科材料，由于 其上级机械和粘合性能。工程化的高粘性外科密封剂可以 可能用于阻止肺部手术后的空气泄漏，并支持新组织形成以修复肺损伤。 叛逃的网站。由于其对天然组织的高粘附性和生物相容性， 该建议具有用于各种手术的潜力，例如心脏病，心血管手术， 和伤口闭合。 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