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.

项目摘要 2018年全球外科胶粘剂和密封胶市场的价值为40.9亿美元，预计为 2026年以9.7％的复合年增长率达到78.9亿美元。中枢神经系统（CNS）的手术 由于全球神经疾病的盛行率很高，因此2016年最大的市场份额。命名 很少有数字，有60万个颅骨手术，120万次腰部手术和170万个创伤性大脑 仅在美国就受伤。密封剂是CNS手术中的第一选择，例如CSF泄漏预防 在传统的组织闭合方法（例如电线，缝合线和钉书钉）上进行的硬脑膜修复。 但是，诸如Duraseal®和Tisseel®之类的传统密封剂远非脑部手术中的满意厂 它们弱的湿组织粘附强度和快速降解，即使用作其他组织的调节器 移植物或尿道成形术设备。结果，对手术密封剂和脑外科手术粘合剂的需求具有 呈指数式复活，使Aleo BME的BP胶产品是渗透这种不断增长的巨大机会 利基市场。 Aleo BME在发现有趣的组织粘附机制方面取得了重大进展 为了开发BP胶并确定了使用BP胶作为脑脊液（CSF）的可行性 大鼠和猪颅骨切开术模型的泄漏预防和硬脑膜修复。 BP胶是由A-B公式组成的 完全合成和可降解的水传播聚氨酯（WPU）纳米粒子分散溶液 反击。 BP胶水粘附机制是通过 WPU（+）和WPU（ - ）纳米颗粒渗透并渗透到组织表面，然后在离子上 交联以在材料/组织界面上形成机械互锁，以进行组织粘合剂和颗粒 包装理论不匹配粒度不匹配（大WPU（+）和小WPU（ - ））起着重要作用 在增强颗粒堆积和干扰以改善粘合剂的粘合剂和粘性强度 （图1）。 BP胶是第一个水性，超高和弹性组织粘合剂，表现出等效的膝盖 Dermabond®（氰基丙烯酸酯）的剪切强度不使用有毒化学交联。期望 使用BP胶的使用可能会消除在脑外科手术中使用其他组织移植物或尿道成形术设备的使用，并且可能 还消除了修复手术后CSF泄漏的复活手术。此SBIR直接的目标 第二阶段是扩大BP胶的制造过程，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，评估其对硬脑膜的效率 在犬颅切开术中维修，并进一步严格验证ISO 10993后BP胶的生物相容性 提交FDA提交。这第二阶段的成功将有助于Aleo BME确保进一步的调查，并 建立业务合作伙伴关系，并将为成功的FDA前市场批准（PMA）铺平道路 应用和技术商业化。