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.

项目摘要/摘要 在美国，每年有超过900,000次心脏手术，其中20％以上是重新手术。尽管 手术已经变得更安全，超过70％的重新手术患者会有严重的粘附，以至于 将心脏融合到胸腔中的其他组织。心脏粘连会损害心脏功能并抑制手术 重新手术程序的访问，导致死亡率增加，发病率，手术复杂性，工作时间， 和医院费用。虽然已经在动物和人类中研究了各种不同的材料，但没有 迄今为止，材料能够预防心脏后手术后的粘附形成。主 尝试减少心脏粘附的方法包括药物，物理屏障和聚合物溶液。 药物破坏对伤口愈合至关重要的有益的生化途径，并且不能实现足够的药物 集中在行动地点。由于降解问题和 需要缝合线。聚合物溶液需要过多的体积，具有高肿胀（导致心脏 填塞），寿命短和/或从心脏中移出。考虑到这些局限性，TissueShield是 与心脏外科医生合作设计和开发。我们建议开发和临床翻译 TissueShield，一种新型的一次性，即现成的，无菌，双室，双注射器可喷水凝胶，以防止 术后心脏粘连。 TissueShield由快速形成的聚（乙二醇）（PEG）组成 由氧电键交联的水凝胶，包括组织结合部分，以确保产物保留 坚持心脏。我们的方法是一个3组分的聚合物系统，可以轻松地直接喷洒到 心脏在几秒钟内形成坚固的抗粘附层。该系统已经被优化以控制 防止粘附和不干扰大鼠心脏功能的肿胀和降解时间的程度 心脏粘连模型和猪模型中最初的小型试点研究。尚无产品显示 我们的特征（组织粘合剂，低肿胀和寿命）。在此，目的是为临床准备组织膜 通过建立临床前安全，过渡到商业上可行的两个室系统的试验， 完成产品开发，并扩展和转移制造。 TissueShield将是第一个 可商购的可喷涂抗粘附产品专门用于预防心脏粘连。