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

SBIR Direct Phase II：用于硬脑膜修复的自然双相胶水

• 批准号: 10489915
• 负责人: Chao Liu
• 金额: $ 89.56万
• 依托单位: ALEO BME, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10489915
• 关键词: Adhesions; Adhesives; Adjuvant; Animals; Businesses; Canis familiaris; Cephalic; Cerebrospinal Fluid; Clinical Trials; Craniotomy; Cyanoacrylates; Dermabond; Development; Devices; Disease; Dura Mater; Elastic Tissue; Evaluation; Family suidae; Fibrin Tissue Adhesive; Formulation; Future; Glues; Goals; Hedera helix; High Prevalence; In Vitro; Investments; Mechanics; Methods; Modeling; Names; Nature; Neuraxis; Operative Surgical Procedures; Particle Size; Persons; Phase; Play; Poison; Polyurethanes; Prevention; Production; Rattus; Role; Safety; Secure; Shear Strength; Small Business Innovation Research Grant; Sterilization; Surface; Surgical sutures; Technology; Tissue Adhesives; Tissue Grafts; Tissues; Traumatic Brain Injury; aqueous; biomaterial compatibility; brain surgery; cohesion; commercialization; crosslink; efficacy evaluation; experience; improved; in vivo; manufacturing process; manufacturing scale-up; nanoparticle; particle; prevent; relating to nervous system; repaired; scaffold; scale up; sealant; success; theories; tool; waterborne

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.

项目概要 2018 年全球手术粘合剂和密封剂市场价值 40.9 亿美元，预计 到 2026 年，中枢神经系统 (CNS) 手术将达到 78.9 亿美元，复合年增长率为 9.7%。 由于全球神经疾病的高发病率，2016 年市场份额最大。 几个数字，颅骨手术60万例，腰椎手术120万例，脑外伤手术170万例 仅在美国，密封剂就是中枢神经系统手术的第一选择，例如预防脑脊液泄漏。 脑外科手术中的硬脑膜修复，优于传统的组织闭合方法，如金属丝、缝合线和钉书钉。 然而，由于 DuraSeal® 和 Tisseel® 等传统密封剂在脑部手术中的效果远不能令人满意。 它们的湿组织粘附强度较弱且降解迅速，甚至用作其他组织的佐剂时也是如此 因此，对脑外科手术密封剂和粘合剂的需求有所增加。 呈指数级增长，为 Aleo BME 的 BP Glue 产品提供了渗透这一不断增长的市场的巨大机会 Aleo BME 在发现有趣的组织粘附机制方面取得了重大进展。 开发 BP Glue 并确立了将 BP Glue 用于脑脊液 (CSF) 的可行性 BP Glue 是一种 A-B 配方，用于大鼠和猪开颅手术模型的渗漏预防和硬脑膜修复。 全合成、可降解的水性聚氨酯 (WPU) 纳米粒子分散体解决方案 BP胶粘合机制是通过English-Ivy粘合机制的独特结合。 其中WPU（+）和WPU（-）纳米粒子渗透并渗透到组织表面，然后离子化 交联以在材料/组织界面处形成机械联锁，以实现组织粘附和颗粒 颗粒尺寸不匹配（大 WPU (+) 和小 WPU (-)）发挥重要作用的堆积理论 增强颗粒堆积和融合，以提高粘合剂的粘合强度和内聚强度 （图 1） BP Glue 是第一种具有同等搭接效果的水性超强弹性组织粘合剂。 剪切强度达到 Dermabond®（氰基丙烯酸酯），无需使用有毒化学交联。 使用 BP Glue 可以消除在脑部手术中使用其他组织移植物或硬脑膜成形术装置，并且可能 还消除了修复术后脑脊液漏的手术。 SBIR Direct 的目标。 第二阶段是扩大 BP Glue 的制造工艺，开发 BP Glue 输送工具，验证 扩大生产规模，了解灭菌对 BP Glue 功能的影响，评估其对硬脑膜的功效 犬开颅手术中的修复，并按照 ISO 10993 进一步严格验证 BP Glue 的生物相容性 第二阶段的成功将有助于 Aleo BME 进一步获得投资和支持。 发展业务合作伙伴关系，将为成功获得 FDA 上市前批准 (PMA) 铺平道路 应用和技术商业化。