SBIR Direct Phase II: Nature Inspired Biphasic Glue for Dura Repair

项目摘要 2018年全球外科胶粘剂和密封剂市场价值为40.9亿美元，预计将 2026年达到78.9亿美元，复合年增长率为9.7%。中枢神经系统(CNS)手术占 由于全球神经疾病的高度流行，2016年的市场份额最大。要命名一位 数字很少，60万例颅脑手术，120万例腰椎手术，170万例脑外伤 仅在美国就有受伤事件。封闭剂是中枢神经系统手术的首选，如防止脑脊液渗漏 以及脑外科手术中的硬脑膜修复，而不是传统的组织闭合方法，如钢丝、缝合和缝合。 然而，传统的封闭剂如DuraSeal®和Tisseel®在脑外科手术中远远不能令人满意，因为 它们的湿组织粘附力弱，降解快，甚至当用作其他组织的佐剂时 移植物或硬脑膜成形术装置。因此，脑外科手术用密封胶和粘合剂的需求 成倍增长，给了Aleo BME的BP Glue产品一个巨大的机会来渗透这个不断增长的 利基市场。Aleo BME在发现一种有趣的组织黏附机制方面取得了重大进展 为BP胶的开发，建立了BP胶用于脑脊液的可行性 大鼠和猪开颅手术模型的防渗漏和硬脑膜修复。BP胶是一种A-B配方，由 完全合成和可降解的水性聚氨酯(WPU)纳米粒子分散体解决方案 反离子。BP粘胶机构是英式常春藤粘合机构的独特组合，通过 哪种WPU(+)和WPU(-)纳米粒子穿透和渗透到组织表面，然后离子 交联化以在材料/组织界面形成用于组织黏附和颗粒的机械互锁 通过堆积理论，颗粒大小不匹配(大WPU(+)和小WPU(-))起着重要作用 在加强颗粒堆积和粘接以提高胶粘剂的粘合强度和粘合强度方面 (图1)。BP胶是第一种展示等值LAP的水性、超强和弹性组织粘合剂 无需使用有毒化学交联剂即可将剪切强度提高到Dermabond®(氰基丙烯酸酯)。预计将会有 使用BP胶可以在脑外科手术中消除其他组织移植物或硬脑膜成形术设备的使用，并可能 同时取消翻修手术，以修复术后脑脊液漏。此SBIR Direct的目标 第二阶段是扩大BP胶水的制造工艺，开发BP胶水输送工具，验证 扩大生产，了解灭菌对BP胶功能的影响，评估其对硬脑膜的疗效 在犬开颅手术中进行修复，并进一步严格验证BP胶的生物相容性，符合ISO 10993 关于FDA提交的文件。这一第二阶段的成功将帮助Aleo BME获得更多投资和 发展业务伙伴关系，并将为FDA成功获得上市前批准(PMA)铺平道路 应用和技术商业化。

Project Summary The global market for surgical adhesives and sealants was valued at USD 4.09 billion in 2018 and projected to reach USD 7.89 billion in 2026 at a CAGR of 9.7%. Surgeries in central nervous system (CNS) accounted for the largest market share in the year 2016, owing to a high prevalence of neural disorders globally. To name a few numbers, there are 600K cranial surgeries, 1.2 million lumbar surgeries, and 1.7 million traumatic brain injuries in the U.S. alone. Sealants are the number one choice in CNS surgeries, such as CSF leak prevention and dura repair in brain surgeries, over traditional tissue closure methods such as wires, sutures, and staples. However, traditional sealants such as DuraSeal® and Tisseel® are far from satisfactory in brain surgeries due to their weak wet tissue adhesion strength and rapid degradation and even when used as adjuvants to other tissue grafts or duraplasty devices. As a result, demand for surgical sealants and adhesives for brain surgeries has risen exponentially, giving Aleo BME’s BP Glue product a huge opportunity to penetrate this ever-increasing niche market. Aleo BME has made significant progress in discovering an interesting tissue adhesion mechanism for the development of BP Glue and established the feasibility of using BP Glue for cerebrospinal fluid (CSF) leak prevention and dura repair in rat and pig craniotomy models. BP Glue is an A-B formulation composed of fully synthetic and degradable water-borne polyurethane (WPU) nanoparticle dispersion solutions with counterions. BP Glue adhesion mechanism is a unique combination of English-Ivy adhesion mechanism through which WPU (+) and WPU (-) nanoparticles penetrate and permeate onto tissue surfaces and then ionically crosslinked to form a mechanical interlocking at the material/tissue interface for tissue adhesion and particle packing theory through which particle size mismatch (large WPU (+) and small WPU (-)) plays a significant role in enhancing particle packing and interfusion for improving adhesive and cohesive strengths of the adhesive (Fig. 1). BP Glue is the first aqueous, super-strong, and elastic tissue adhesive demonstrating equivalent lap shear strengths to Dermabond® (cyanoacrylate) without using toxic chemical crosslinking. It is expected that the use of BP Glue may eliminate the use of other tissue grafts or duraplasty devices in brain surgeries and may also eliminate the revisional surgeries to fix the post-surgical CSF leaks. The objectives of this SBIR Direct Phase II are to scale-up the manufacturing processes of BP Glue, develop BP Glue delivery tool, validate the scale-up productions, understand the impact of sterilization on BP Glue functions, evaluate its efficacy for dura repair in a canine craniotomy, and further rigorously validate the biocompatibility of BP Glue following ISO 10993 toward FDA submissions. The success of this Phase II will help Aleo BME secure further investments and develop business partnerships and will pave the way toward a successful FDA Premarket Approval (PMA) application and technology commercialization.