Engineering highly elastic surgical sealants with hemostatic properties

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，外科手术对脆弱的软组织，如肺、肝脏和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，如机械柔韧性低、毒性作用或有毒降解产物、粘附性差等 体力，以及无法控制出血。因此，它们都不能满足所有必要的替换需求 缝合线和订书机。理想的手术密封剂要求具有柔韧性，以适应本地的动态运动 组织，具有良好的生物兼容性和受控的生物降解性，提供高粘合强度和耐破碎性 压力特别是在存在体液的情况下，并表现出止血特性，防止广泛 失血过多。在这项提案中，我们的目标是设计一种新型的、高度粘合和止血的水凝胶外科手术。 从可见光激活的密封剂，修饰的重组人蛋白甲基丙烯酰原弹性蛋白(Metro)和 止血硅酸盐纳米粒(SNS)。我们将把经过改造的麦德龙水凝胶与SNS进行物理混合，以 形成具有高度粘附性和增强止血性能的Metro/SN复合水凝胶。到时候我们会的 评估工程外科材料作为止血封闭剂在小动物和大动物中的功能 模特们。我们的初步数据表明，这种材料优于市场上现有的产品，而且 可以产生一种改变模式的手术材料，由于其优越的机械性能而无需缝合， 粘附性和止血性能。设计的高粘性和止血外科密封剂可以 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。由于工程复合水凝胶的高度可调性能，预计 该系统还可用于各种手术，如吻合术、心血管手术和创伤。 结案了。

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, and 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 flexibility, toxicity effects or toxic degradation products, poor adhesive strength, and inability to control bleeding. Therefore, none of them meet all the necessary needs to replace sutures and staples. An ideal surgical sealant is required to be flexible to adapt with dynamic movement of native tissues, have excellent biocompatibility and controlled biodegradability, provide high adhesive strength and burst pressure particularly in the presence of body fluids, and demonstrate hemostatic properties to prevent extensive blood loss. In this proposal, we aim to engineer a novel, highly adhesive and hemostatic hydrogel-based surgical sealant from a visible light activated, modified recombinant human protein methacryloyl tropoelastin (MeTro) and hemostatic silicate nanoparticles (SNs). We will physically blend the engineered MeTro hydrogels with SNs to form MeTro/SN composite hydrogels with highly adhesion and enhanced hemostatic performance. We will then evaluate the function of the engineered surgical material as a hemostatic 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, adhesive, and hemostatic properties. The engineered highly adhesive and hemostatic 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 the highly tunable properties of the engineered composite hydrogels, it is expected that this system can also be used in various procedures such as anastomoses, cardiovascular surgeries, and wound closure.