SBIR-STTR Award

The brain is a highly vascularized organ and any surgical procedure performed in it inevitably disrupts its delicate vasculature;addressing bleeding during brain surgery is of utmost importance, as excessive bleeding within the confined space of the skull can quickly lead to serious debilitating complications and death. Conventional techniques for bleeding control have very limited utility for the brain. The standard for bleeding control during brain surgery has practically not changed for many decades, with oxidized cellulose, gelatin and collagen as the commonly used materials;thrombin is often deployed in conjunction with these materials to hasten hemostasis. Collectively, the main issues associate with these approaches are, (i) require preparation, (ii) non-conformal and non-adhesive to the site of application, (iii) lack transparency and thus limited capacity for visualizing the status of hemostasis, (iv) material of blood/mammalian origin and thus the risk of disease transmission, and (v) swelling. In this project, we will formulate a transparent, biocompatible/biodegradable and formable/conformable/adhesive hemostatic agent aiming for controlling the bleeding during brain surgery. In parallel, we will validate the lack of cytotoxicity potential of the hemostatic agent;this will be followed by in vivo biocompatibility testing. The in vivo efficacy validation study will be performed in rat brain surgery model. , ,

Public Health Relevance:
Over 130,000 neurosurgical procedures are performed on the brain in the US each year. The brain is rich in delicate blood vessels and any surgical procedure performed in it inevitably disrupts the structure. Addressing bleeding during brain surgery is of utmost importance, as excessive bleeding within the brain can quickly lead to serious debilitating complications and death. Due to the small size of the vessels and the delicacy of the tissue, typical techniques such as ligature and electrocautery commonly utilized for controlling bleeding vessels in various surgical procedures have very limited applicability in the brain. The standard for bleeding control during brain surgery has practically not changed for many decades;many of the surgical adjuncts currently being utilized to control bleeding are not optimized for brain surgery and many of these products are blood or mammalian derived, which carry the risk of disease transmission. The goal of this project is to develop a non-blood, non-mammalian and natural material based hemostatic agent optimized for controlling bleeding during brain surgery.

Thesaurus Terms:
Address;Adhesives;Area;Arteries;Arterioles;Biocompatible;Bleeding;Blood;Blood Vessels;Body Tissues;Bone Structure Of Cranium;Brain;Brain Hemorrhage;Cellulose;Cephalic;Cessation Of Life;Chitosan;Collagen;Common Rat Strains;Confined Spaces;Cranial;Cranium;Death;Dextrans;Diffuse;Electrocautery;Electrocoagulation;Encephalon;Encephalons;Endocavitary Fulguration;Fulguration;Galvanocautery;Gelatin;Goals;Hemorrhage;Hemostasis;Hemostatic Agents;Hemostatic Function;Hemostatics;Hydrogels;In Situ;In Vitro;Injury;Lead;Ligature;Lytotoxicity;Mammals, Rats;Methods And Techniques;Methods, Other;Modeling;Nervous System, Brain;Neurosurgical Procedures;Operation;Operative Procedures;Operative Surgical Procedures;Organ;Pb Element;Performance;Poliglusam;Polyanhydroglucuronic Acid;Preparation;Rat;Rattus;Reticuloendothelial System, Blood;Risk;Science Of Neurosurgery;Site;Skull;Structure;Structure Of Arteriole;Surgery, Neurological;Surgical;Surgical Diathermy;Surgical Interventions;Surgical Procedure;Swelling;Techniques;Testing;Thermocoagulation;Thrombase;Thrombin;Tissues;Validation;Alpha-Cellulose;Arteriole;Base;Biocompatibility;Biomaterial Compatibility;Blood Loss;Blood Product;Brain Surgery;Communicable Disease Transmission;Cranium;Cytotoxicity;Dextran;Disease Transmission;Fibrinogenase;Heavy Metal Pb;Heavy Metal Lead;Hemorrhagic Stroke;Implantation;In Vivo;Infectious Disease Transmission;Neurosurgery;Public Health Relevance;Surgery;Validation Studies;Vascular

Bleeding control during brain surgery is of utmost importance, as uncontrolled bleeding inside the confined intracranial space can quickly degenerate into debilitating complications and death. Ligature is usually not possible in the braindue both to the small size of the vessels and the delicacy of the tissue as the majority of bleedings during neurosurgery is the topical diffuse/oozing type bleeding. The methods for bleeding control during brain surgery has practically not changed for decades; surgical aids that work by pressure, absorption, and/or chemical mediated mechanisms are deployed for hemostasis during brain surgery. The shortcomings of these products include: (i) require preparation, (ii) non-conformal/non-adhesive to the surgical site, (iii) require manual pressure, (iv) lack transparency - limited capacity to visualize the hemostasis status, (v) materials of bloo and/or mammalian origin - risk of disease transmission, and (v) swelling. Importantly, the major inadequacies of these products are slow acting leading to prolonging surgery (risk and morbidity) and often produce inconsistent results. Gelatin foam saturated with thrombin solution in conjunction with applying pressure is still the current gold-standard to stop diffuse bleeding; the process requires a coordinated deployment of at least four products including gelatin foam, thrombin, cottonoids, and suction. We are developing a non-mammalian/non-blood derived biocompatible and biodegradable, in situ gelable adhesive/formable/conformable and non-swelling transparent hydrogel that requires no preparation, for cranial hemostasis, it is non-chemically mediated and can quickly stop bleeding on contact without any adjuncts. [A transparent agent, capable of achieving hemostasis rapidly, enables the surgeons to determine the status of hemostasis and speed up the decision of moving onto the next step of the surgery.] Accelerating surgery with a highly competitively priced hemostatic agent will eventually result in considerable cost saving on operating room time and reduction of morbidity through shortening of surgery and general anesthesia. Our product conforms to the new healthcare economics where insurers are increasingly demanding superior products at lower costs. A prototype agent was developed in the Phase I of this project and its efficacy and performance criteria have been experimentally defined. In Phase II, we will continue to develop the hemostat product. The major goals are: (i) reduce the product endotoxin burden to comply with FDA's requirement, (ii) maximize the product's consistency, (iii) streamline the current methodologies to reduce the future production costs, (iv) develop a non-power assisted dispenser for the product to facilitate clinical use, (v) production of GLP grade materials, (vi) ISO10993 biocompatibility and toxicology validation, and (vii) in vivo pilot testing of the hemostat in a large animal cranial model.

Thesaurus Terms:
Absorption;Adhesiveness;Adhesives;Adverse Effects;Africa;Animals;Biocompatible;Biomaterial Compatibility;Blood;Brain;Brain Surgery;Canis Familiaris;Cephalic;Cessation Of Life;Chemicals;China;Chitosan;Classification;Clinical;Coagulation Process;Contracts;Cost;Design;Development;Devices;Dextran;Dextrans;Diffuse;Disease Transmission;Endotoxins;Experimental Designs;Fee-For-Service Plans;Future;Gelatin;General Anesthesia;Goals;Gold;Health Care Economics;Healthcare Systems;Hemorrhage;Hemostatic Agents;Hemostatic Function;Hospitals;Hour;Hydrogels;Improved;In Situ;In Vivo;India;Injury;Insurance Carriers;Interest;Japan;Label;Lead;Ligature;Longevity;Manuals;Manufacturer Name;Marketing;Mediating;Methodology;Methods;Modeling;Molecular Weight;Morbidity - Disease Rate;Neurosurgery;Operating Rooms;Operative Surgical Procedures;Payment;Performance;Phase;Pilot Projects;Pre-Clinical;Preparation;Pressure;Price;Privileged Communications;Process;Production;Protocols Documentation;Prototype;Public Health Relevance;Recovery;Research Study;Risk;Russia;Sahara;Site;Solutions;Speed (Motion);Staging;Structure;Suction;Surgeon;Swelling;System;Techniques;Testing;Thrombin;Time;Tissues;Toxicology;Validation;Viscosity;Work;