Engineering highly elastic surgical sealants with hemostatic properties

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、肝和血管的损伤， 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，如低的机械柔韧性，毒性作用或毒性降解产物，粘合性差， 无力控制出血因此，它们都不能满足所有必要的需求， 缝合和斯台普斯理想的外科密封剂需要是柔性的，以适应天然材料的动态运动。 组织，具有优异的生物相容性和可控的生物降解性，提供高粘合强度和破裂 压力，特别是在体液的存在下，并表现出止血性能，以防止广泛的 失血过多在这项提案中，我们的目标是设计一种新型的，高粘性和止血的水凝胶为基础的外科手术， 来自可见光激活的、修饰的重组人蛋白甲基丙烯酰原弹性蛋白（MeTro）的密封剂， 止血硅酸盐纳米颗粒（SN）。我们将物理混合工程MeTro水凝胶与SN， 形成具有高粘附性和增强的止血性能的MeTro/SN复合水凝胶。然后我们将 在小型和大型动物中评价工程外科材料作为止血密封剂的功能 模型我们的初步数据表明，这种材料上级市场上现有的产品， 可以产生一种范式转换的外科材料，由于其上级机械性能， 粘合剂和止血性能。工程化的高粘性和止血外科密封剂可以 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。由于工程复合水凝胶的高度可调性质，预期 该系统还可用于各种手术，例如心脏病、心血管手术和创伤， 结束

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.