Engineering highly elastic surgical sealants with hemostatic properties

设计具有止血特性的高弹性手术密封剂

• 批准号: 10089283
• 负责人: Nasim Annabi
• 金额: $ 71.51万
• 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: 2018-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10089283
• 关键词: Address; Adhesions; Adhesives; Air; Anastomosis - action; Animal Model; Area; Binding; Biocompatible Materials; Blood; Blood Coagulation Factor; Blood Vessels; Blood coagulation; Body Fluids; Cardiovascular Surgical Procedures; Charge; Clinic; Clinical; Consumption; Cyanoacrylates; Data; Defect; Development; Devices; Elastic Tissue; Elasticity; Engineering; Environment; Exhibits; Extravasation; Family suidae; Fibrin Tissue Adhesive; Goals; Hemorrhage; Hemostatic Agents; Human; Hydrogels; In Situ; In Vitro; Infection; Ischemia; Light; Liquid substance; Liver; Lung; Mechanics; Methods; Modeling; Movement; Mus; Operative Surgical Procedures; Performance; Physiological; Pleural; Polymers; Procedures; Property; Proteins; Punch Biopsy; Recombinants; Silicates; Site; Surface; Surgeon; Surgical Mesh; Surgical complication; Surgical sutures; Surgical wound; System; Techniques; Thoracic Surgical Procedures; Time; Tissues; Toxic effect; Tropoelastin; Ultraviolet Rays; Visible Radiation; Work; base; biomaterial compatibility; cell injury; crosslink; flexibility; gastrointestinal; healing; implantation; improved; in vivo; in vivo evaluation; injured; nanoparticle; novel; physical property; pressure; prevent; regenerative; repaired; seal; skills; soft tissue; surgery material; wound; wound closure

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.

项目摘要/摘要 每年在全球每年发生大约1.14亿个手术和基于程序的伤口，其中包括3600万 从美国的手术损害到细腻的软组织，例如肺，肝和血管 具有挑战性的维修。当这些组织在手术过程中进行活检或受伤时，它们必须是 使用缝合线，钉书钉或外科手术网植物进行手术重新连接。尽管它们常用于 诊所，这些机械方法与不可避免的组织损伤有关 缺血。这些方法也很耗时，在手术过程中需要外科医生的技能，并且可能 引起手术后并发症，例如感染。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/粘合剂的生物材料通常具有一些限制的缺点 它们的应用，例如低机械柔韧性，毒性效应或有毒降解产物，粘合剂不良 力量，无法控制出血。因此，它们都不满足更换的所有必要需求 缝合线和钉书钉。理想的手术密封剂必须灵活以适应天然的动态运动 组织具有出色的生物相容性和受控的生物降解性，可提供高粘合强度和爆发 尤其是在体液存在的压力，并表现出止血特性以防止广泛 失血。在此提案中，我们旨在设计一种新颖的，高度粘合和止血水凝胶的手术 来自可见光，改良的重组人蛋白甲基丙烯酰tropoelastin（Metro）的密封剂和 止血硅酸盐纳米颗粒（SNS）。我们将实际将工程化的地铁凝胶与SNS融合到 形成具有高度粘附和增强止血性能的地铁/SN复合水凝胶。然后我们会 评估工程外科手术材料作为小动物和大型动物的止血密封剂的功能 型号。我们的初步数据表明，该材料优于市场上现有产品， 可能会产生一种范式移动外科手术材料，该手术材料由于其优质的机械性而可能不需要缝合 粘合剂和止血特性。高度粘合剂和止血手术密封剂可以是 可能用于阻止肺手术后停止空气泄漏，还支持新的组织形成以修复 缺陷的站点。由于工程复合材料水凝胶的高度可调节性能，预计 该系统也可以用于各种过程中，例如吻合，心血管手术和伤口 关闭。

项目成果

Harnessing the Wide-range Strain Sensitivity of Bilayered PEDOT:PSS Films for Wearable Health Monitoring.

• DOI: 10.1016/j.matt.2021.06.034
• 发表时间: 2021-09-01
• 期刊: Matter
• 影响因子: 18.9
• 作者: Liu H;Zhang S;Li Z;Lu TJ;Lin H;Zhu Y;Ahadian S;Emaminejad S;Dokmeci MR;Xu F;Khademhosseini A
• 通讯作者: Khademhosseini A

An All-In-One Transient Theranostic Platform for Intelligent Management of Hemorrhage.

• DOI: 10.1002/advs.202301406
• 发表时间: 2023-08
• 期刊: ADVANCED SCIENCE
• 影响因子: 15.1
• 作者: Haghniaz, Reihaneh;Gangrade, Ankit;Montazerian, Hossein;Zarei, Fahimeh;Ermis, Menekse;Li, Zijie;Du, Yuxuan;Khosravi, Safoora;de Barros, Natan Roberto;Mandal, Kalpana;Rashad, Ahmad;Zehtabi, Fatemeh;Li, Jinghang;Dokmeci, Mehmet R.;Kim, Han-Jun;Khademhosseini, Ali;Zhu, Yangzhi
• 通讯作者: Zhu, Yangzhi