Development of a single-use, ready-to-use, sterile, dual chamber, dual syringe sprayable hydrogel to prevent postsurgical cardiac adhesions.

开发一次性、即用型、无菌、双室、双注射器可喷雾水凝胶，以防止术后心脏粘连。

• 批准号: 10669829
• 负责人: Gregory Grover
• 金额: $ 35万
• 依托单位: KARIOS TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10669829
• 关键词: Address; Adhesions; Agreement; Aldehydes; Animals; Binding; Biochemical Pathway; Cardiac; Cardiac Surgery procedures; Cardiac Tamponade; Catechols; Cell Adhesion; Chest; Chronic; Clinical; Clinical Trials; Collaborations; Complement Activation; Contracts; Data; Development; Devices; Engineering; Ensure; Family suidae; Feasibility Studies; Feedback; Filtration; Freeze Drying; Freezing; Funding; Heart; Hemolysis; Hospital Costs; Human; Hydrogels; Impairment; In Vitro; Life; Longevity; Manufacturer; Modeling; Morbidity - disease rate; Operative Surgical Procedures; Oximes; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Pilot Projects; Polyethylene Glycols; Polymers; Prevention; Procedures; Process; Production; Published Comment; RTN4 gene; Rattus; Repeat Surgery; Running; Safety; Secure; Serious Adverse Event; Severities; Site; Source; Sterility; Surgeon; Surgical sutures; Swelling; Syringes; System; Testing; Time; Tissues; Toxic effect; Translating; Vendor; Work; acute toxicity; arm; clinical efficacy; crosslink; design; ethylene glycol; evaluation/testing; feasibility testing; genotoxicity; heart function; hemocompatibility; implantation; improved; in vivo; interest; irritation; manufacture; manufacturing process; meetings; mortality; novel; porcine model; preclinical safety; prevent; product development; prototype; safety study; scale up; standard of care; sterility testing; thrombogenesis; usability; viscoelasticity; wound healing

PROJECT SUMMARY/ABSTRACT There are over 900,000 cardiac surgeries per year in the US, of which, over 20% are reoperations. While surgeries have become safer, over 70% of these reoperation patients will have severe adhesions present that fuse the heart to other tissues in the chest cavity. Cardiac adhesions impair cardiac function and inhibit surgical access in reoperation procedures, leading to increased mortality, morbidity, surgery complexity, operating times, and hospital costs. While a variety of different materials have been investigated in animals and humans, no materials, to date, have been capable of preventing adhesion formation post-cardiac surgery. The main approaches for attempting to reduce cardiac adhesions include drugs, physical barriers, and polymer solutions. Drugs disrupt beneficial biochemical pathways vital for wound healing and do not achieve adequate drug concentration at the site of action. Barriers have shown limited clinical efficacy due to degradation issues and requiring sutures. Polymer solutions require excessively large volumes, possess high swelling (leading to cardiac tamponade), short lifespans, and/or dislodge from the heart. Considering these limitations, TissueShield was engineered and developed in collaboration with cardiac surgeons. We propose to develop and clinically translate TissueShield, a novel single-use, ready-to-use, sterile, dual chamber, dual syringe sprayable hydrogel to prevent postsurgical cardiac adhesions. TissueShield is composed of a rapidly forming poly(ethylene glycol) (PEG) hydrogel that is cross-linked by oxime bonds and includes a tissue binding moiety to ensure the product remains adhered to the heart. Our approach is a 3-component polymer system that can be easily sprayed directly onto the heart forming a robust anti-adhesion layer within seconds. This system has already been optimized to control the degree of swelling and degradation time to prevent adhesions and to not interfere with cardiac function in rat cardiac adhesions models and an initial small pilot study in a porcine model. No product has been shown to have our features (tissue binder, low swelling, and lifespan). Herein, the objective is to prepare TissueShield for clinical trials by establishing preclinical safety, transitioning to and testing a commercially viable two chamber system, completing product development, and scaling up and transferring manufacturing. TissueShield will be the first commercially available sprayable anti-adhesions product designed specifically for preventing cardiac adhesions.

项目概要/摘要 美国每年有超过90万例心脏手术，其中超过20%是再次手术。尽管 手术变得更加安全，超过70%的再次手术患者会出现严重粘连， 将心脏与胸腔内的其他组织融合。心脏粘连损害心脏功能并阻碍手术 再次手术程序的可及性，导致死亡率、发病率、手术复杂性、手术时间增加， 和医院费用。虽然已经在动物和人类身上研究了各种不同的材料，但没有 迄今为止，材料已经能够防止心脏手术后粘连的形成。主要 尝试减少心脏粘连的方法包括药物、物理屏障和聚合物溶液。 药物会破坏对伤口愈合至关重要的有益生化途径，并且无法获得足够的药物 集中在作用部位。由于降解问题和屏障的临床功效有限 需要缝合。聚合物溶液需要太大的体积，具有高膨胀性（导致心脏 填塞）、寿命短和/或从心脏脱落。考虑到这些限制，TissueShield 与心脏外科医生合作设计和开发。我们建议开发并临床转化 TissueShield，一种新型一次性、即用型、无菌、双室、双注射器可喷雾水凝胶，可预防 术后心脏粘连。 TissueShield 由快速成型的聚乙二醇 (PEG) 组成 通过肟键交联的水凝胶，包含组织结合部分以确保产品保持不变 坚守于心。我们的方法是一种三组分聚合物系统，可以轻松直接喷涂到 心脏在几秒钟内形成坚固的防粘连层。该系统已经过优化以控制 肿胀程度和降解时间以防止粘连且不干扰大鼠的心脏功能 心脏粘连模型和猪模型的初步小型试点研究。没有产品被证明具有 我们的特点（组织粘合剂、低膨胀和使用寿命）。本文的目标是为临床准备 TissueShield 通过建立临床前安全性、过渡到并测试商业上可行的两室系统进行试验， 完成产品开发、扩大生产规模并转移生产。 TissueShield 将是第一个 市售可喷雾防粘连产品，专为预防心脏粘连而设计。