SBIR-STTR Award

Direct to Phase II

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.

Public Health Relevance Statement:
Project Narrative Each year, 1.7 million people in the US experience a traumatic brain injury, the primary cause of dural damage and subsequent CSF leaks. Built on the success of SBIR Phase I project, the primary goal of this SBIR Phase II proposal is to further develop Aleo BME's proprietary super-strong and elastic aqueous tissue adhesive, Biphasic Glue (BP Glue) and evaluate its biocompatibility and efficacy for dura repair in a canine craniotomy model toward future clinical trials and FDA submission.

Project Terms:
Adhesions; Adhesives; Animals; Cerebrospinal Fluid; cerebral spinal fluid; spinal fluid; Clinical Trials; Craniotomy; skull incision; Cyanoacrylates; Disease; Disorder; Canis familiaris; Canine Species; Dogs; Dogs Mammals; canine; domestic dog; Dura Mater; Dura; Elastic Tissue; Fibrin Tissue Adhesive; Autologous Fibrin Tissue Adhesive; Fibrin Adhesive; Fibrin Glue; Fibrin Sealant; Fibrin Sealant System; Fibrinogen Adhesive; Tissel; tisseel; Future; Glues; Goals; In Vitro; Investments; Methods; Persons; Names; Particle Size; Play; Toxic Chemical; Toxic Substance; toxic compound; Poison; Ostamer; Pellethane; Polyisocyanates; Polyurethanes; Production; Common Rat Strains; Rat; Rats Mammals; Rattus; social role; Role; Safety; Sutures; Surgical sutures; Pigs; Suidae; Swine; porcine; suid; Family suidae; Technology; Tissue Adhesives; Tissues; Body Tissues; Businesses; crosslink; cross-link; improved; brain surgery; Cephalic; Cranial; Surface; repaired; repair; Phase; Evaluation; English Ivy; Hedera helix; tool; scaffolding; scaffold; tissue grafting; Tissue Grafts; Nature; mechanical; Mechanics; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Operative Surgical Procedures; biocompatibility; biomaterial compatibility; experience; particle; success; cohesion; neural; relating to nervous system; aqueous; Prevention; Devices; Modeling; theories; Brain Trauma; traumatic brain damage; Traumatic Brain Injury; Neuraxis; CNS Nervous System; Central Nervous System; Shear Strength; preventing; prevent; High Prevalence; in vivo; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Adjuvant; Development; developmental; Dermabond; efficacy evaluation; efficacy analysis; efficacy assessment; efficacy examination; evaluate efficacy; examine efficacy; nanoparticle; nano particle; nano-sized particle; nanosized particle; manufacturing process; scale up; waterborne; water-borne; commercialization; manufacturing scale-up; Sterilization; Secure; Formulation; sealant