I-Corps: A Sprayable Tissue-Binding Hydrogel to Prevent Postsurgical Cardiac Adhesions

I-Corps：一种可喷雾的组织结合水凝胶，可防止术后心脏粘连

• 批准号: 10741261
• 负责人: Gregory Grover
• 金额: $ 5.5万
• 依托单位: KARIOS TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-09 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10741261
• 关键词: Adhesions; Adhesives; Adult; Animal Model; Animals; Binding; Biochemical Pathway; Businesses; Cardiac; Cardiac Surgery procedures; Cardiovascular system; Child; Congenital Heart Defects; Coronary; Deposition; Development; Ensure; Excision; Fibrin; Freedom; Gel; Heart; Hospital Costs; Human; Hydrogels; Inflammation; Injectable; Injury; Innovation Corps; Liquid substance; Longevity; Marketing; Mediastinal; Membrane; Modeling; Morbidity - disease rate; Operative Surgical Procedures; Oximes; Patients; Pharmaceutical Preparations; Pilot Projects; Polymers; Prevention; Procedures; Process; Property; Rattus; Reaction; Repeat Surgery; Safety; Site; Surface; Surgical sutures; Swelling; System; Time; Tissues; Vascularization; adhesion process; commercialization; crosslink; design; ethylene glycol; experience; heart function; mortality; novel; novel strategies; operation; pediatric patients; pharmacologic; porcine model; pre-clinical; prevent; repaired; standard of care; surgical risk; wound healing

PROJECT SUMMARY/ABSTRACT Currently, there are no approved and available products to prevent postsurgical cardiac adhesions and hence no standard of care. This is a large unmet need since there are >500,000 open-heart surgeries/year (projected to grow to >850,000 by 2030) and >100,000 of these are reoperations and ~30,000 are on children with congenital heart defects. Reoperations in cardiac surgery have increased surgical risks due to cardiac adhesions, which increase the difficulty of sternal reentry, hinder visibility of mediastinal tissues, and increase potential injury to cardiovascular tissues. Injuries occurring to adhesion removal triples the mortality of reoperation patients, increase operation time and hospital costs. This is especially relevant for pediatric patients with congenital heart defects who will experience multiple surgeries over their lifetime. Cardiac adhesions have also become a common problem in adults who experience multiple surgeries to repair or replace valves or to undergo coronary revascularization procedures. Two main approaches exist for reducing or attempting to prevent cardiac adhesions: pharmacological therapy and physical barriers. Drugs that prevent or reverse adhesion processes disrupt biochemical pathways of inflammation and fibrin deposition. Unfortunately, these processes are also vital for wound healing. Achieving adequate drug concentration at the site of action is also challenging due to fluid drains. A more viable approach is the use of a physical barrier to prevent fusion of the heart to surrounding tissues. The barriers can be either preformed membranes or injectable hydrogels (fast gelling liquids). Preformed anti-adhesive materials need to be cut before application to the tissue, and must be sutured/packed into place to prevent slippage. Injectable hydrogels allow the freedom of applying material where needed with spraying. The precursor components are capable of quickly reacting, forming a protective gel on the surface of the tissue. 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. Herein, we propose a new approach to prevent postsurgical cardiac adhesions using TissueShield™, which 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- 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 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). The objective herein is to optimize the delivery volume and evaluate preliminary efficacy and safety of TissueShield™ of in a large animal cardiac adhesions model. This will be the first sprayable anti-adhesions product designed specifically for preventing cardiac adhesions. Karios has formed an I-Corp team to validate our market assumptions, refine our overall commercialization strategy, and to better understand the market and market drivers.

项目概要/摘要 目前，还没有批准和可用的产品来预防术后心脏粘连，因此 没有护理标准，这是一个巨大的未满足的需求，因为每年有超过 500,000 例心脏直视手术（预计）。 到 2030 年将增长到超过 850,000 例），其中超过 100,000 例需要再次手术，约 30,000 例接受患有以下疾病的儿童 先天性心脏缺陷心脏手术中的再次手术会增加由于心脏原因而导致的手术风险。 粘连，增加胸骨折返的难度，阻碍纵隔组织的可见度，并增加 去除粘连时对心血管组织的潜在损伤使死亡率增加三倍。 再次手术患者，增加手术时间和住院费用，这对于儿科患者尤其相关。 患有先天性心脏病的人一生中会经历多次手术 心脏粘连。 对于经历多次手术来修复或更换瓣膜或 接受冠状动脉血运重建手术。 减少或试图预防心脏粘连有两种主要方法： 药物治疗 预防或逆转粘附过程的药物会破坏粘连的生化途径。 不幸的是，这些过程对于伤口愈合也至关重要。 由于液体引流，在作用部位保持足够的药物浓度也具有挑战性。 是使用物理屏障来防止心脏与周围组织融合。屏障可以是其中之一。 预制膜或可注射水凝胶（快速胶凝液体）需要预制防粘材料。 在应用于组织之前进行切割，并且必须缝合/包装到位以防止滑动。 水凝胶允许在需要时自由地喷涂材料。 能够快速反应，在组织表面形成保护凝胶，而各种不同。 已经对动物和人类的材料进行了研究，迄今为止，还没有材料能够预防 心脏手术后粘连形成。 在此，我们提出了一种使用 TissueShield™ 预防术后心脏粘连的新方法，该方法是 由快速形成的聚乙二醇（PEG）水凝胶组成，通过肟键交联， 包括组织结合部分，以确保产品保持粘附在心脏上。我们的方法是 3-。 聚合物系统，可以轻松直接喷涂到心脏上，在心脏内形成坚固的防粘层 该系统已经过优化，可将膨胀程度和降解时间控制在 100 秒内。 在大鼠心脏粘连模型中预防粘连且不干扰心脏功能，并且初始小 在猪模型中进行的初步研究尚未显示出任何产品具有我们的特性（组织粘合剂、低肿胀和 寿命）。目标规格是优化输送量并评估初步功效和安全性。 用于大型动物心脏粘连模型的 TissueShield™ 这将是第一个可喷雾的抗粘连剂。 专为预防心脏粘连而设计的产品。 Karios 组建了一个 I-Corp 团队来验证我们的市场假设，完善我们的整体商业化 战略，并更好地了解市场和市场驱动因素。