Hemorrhage and uncontrolled bleeding are a leading cause of death, and when not fatal can result in adversehealth outcomes with long term negative consequences including organ damage or failure, and coma.Uncontrolled bleeding can arise from a variety of diseases, traumatic injuries, and health conditions, such asatrial fibrillation, which afflicts over 2.6M people in the United States. Most atrial fibrillation patients are requiredto take anticoagulants (ACAs). The standard of care (SOC) for internal hemorrhage is transcatheter embolizationto occlude the bleeding artery or vein, however, there are major drawbacks of currently available methods,including high cost, lack of complete occlusion, reliance on patient coagulation, difficultly of proper administration,imaging artifacts, and the chance of migration or fragmentation of the material. There is a significant unmentneed for embolization materials that are compatible with ACAs, are easy to use, and are effective and safe foruse. To address this need, in this Fast-track proposal Obsidio, Inc is developing an innovative embolicmaterial called shear-thinning biomatieral (STB) that has the qualities required for a versatile andeffective embolic material. STB is ready to use and does not require mixing or preparation, is easy to administervia standard microcatheters, can be delivered over a short or extended time period without fear of clogging thecatheter, does not produce an image artifact after administration, and is comprised of materials that are safe andbiocompatible. Moreover, STB is a more cost-effective option for both patients and hospitals and does not requirethe same level of expertise to administer as other methods.The objective of this Fast-track proposal is todevelop a clinical-grade formulation of STB for peripheral hemorrhage control and initate a designfreeze, demonstrate safety of both the biomaterial and the device through ex vivo and in vivo studies,and complete the testing required by the FDA including biocompatibility studies and GLP animal studies.In Phase I of the Fast-track we propose to finalize STB formulation, validate the safety and efficacy of clinical-grade STB, and evaluate its performance in a non-GLP rodent model. In Phase II of the Fast-track we proposeto validate STB performance in a non-GLP bleeding porcine model of hemorrhage, followed by ISO-10993biocompatbility studies to confirm safety of the biomateirals, including an in vitro in vivo correlation studies todetermine the degradation of STB. Finally, we will conduct GLP studies in a porcine model to characterize theperformance and safety of STB. Successful completion of this work with enable Obsidio to advance to 510kclearance for STB used in peripheral hemorrhage. Overall, development of this novel biomaterial will providephyscians a novel embolization option with superior performance and versatility that will ultimately help to savehundreds of thousands of lives annually.
Public Health Relevance Statement: PROJECT NARRATIVE
Uncontrolled bleeding and hemorrhage is a leading cause of death in United States and can be caused by heart
conditions, traumatic injuries, and vascular malformations. Current treatments have significant drawbacks and
often lead to rebleeding, are not compatible with all patients, and are difficult and cumbersome to administer. To
address this need, Obsidio, Inc is developing an innovative shear thinning biomaterial (STB) that is versatile,
naturally occlusive, has a low risk of migration, fragmentation, or rebleeding, is compatible with imaging, and is
cost-effective and easy to administer to advance our ability to control hemorrhage in all patients alike.
Project Terms: Angiography ; Angiogram ; angiographic imaging ; Animals ; Anti-Inflammatory Agents ; Anti-Inflammatories ; Anti-inflammatory ; Antiinflammatories ; Antiinflammatory Agents ; antiinflammatory ; Anticoagulants ; Anticoagulant Agents ; Anticoagulant Drugs ; blood thinner ; thrombopoiesis inhibitor ; Arteries ; Atrial Fibrillation ; Auricular Fibrillation ; Biocompatible Materials ; Biomaterials ; biological material ; Blood Vessels ; vascular ; Cause of Death ; Coma ; Comatose ; Contrast Media ; Contrast Agent ; Contrast Drugs ; Radiopaque Media ; Correlation Studies ; Statistical Correlation ; Disease ; Disorder ; Therapeutic Embolization ; Embolization Therapy ; Embolotherapy ; embolization ; Fright ; Fear ; femoral artery ; Freedom ; Liberty ; Freezing ; Gelatin ; Health ; Heart ; Blood Tests ; Hematologic Tests ; Hematological Tests ; Hematology Testing ; Hemorrhage ; Bleeding ; blood loss ; Hemostatic Agents ; Hemostatics ; Hepatic artery ; Histology ; Hospitals ; In Vitro ; Interview ; Kidney ; Kidney Urinary System ; renal ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Methods ; Legal patent ; Patents ; Patients ; Pelvis ; Pelvic ; Pelvic Region ; Research Design ; Study Type ; study design ; Risk ; Rodent ; Rodentia ; Rodents Mammals ; Safety ; Structure of splenic artery ; Splenic Artery ; Testing ; Thinness ; Leanness ; Time ; X-Ray Computed Tomography ; CAT scan ; CT X Ray ; CT Xray ; CT imaging ; CT scan ; Computed Tomography ; Tomodensitometry ; X-Ray CAT Scan ; X-Ray Computerized Tomography ; Xray CAT scan ; Xray Computed Tomography ; Xray computerized tomography ; catscan ; computed axial tomography ; computer tomography ; computerized axial tomography ; computerized tomography ; Toxicology ; Ultrasonography ; Echography ; Echotomography ; Medical Ultrasound ; Ultrasonic Imaging ; Ultrasonogram ; Ultrasound Diagnosis ; Ultrasound Medical Imaging ; Ultrasound Test ; diagnostic ultrasound ; sonogram ; sonography ; sound measurement ; ultrasound ; ultrasound imaging ; ultrasound scanning ; United States ; Veins ; Work ; Roentgen Rays ; X-Radiation ; X-Ray Radiation ; X-ray ; Xray ; cytokine ; Measures ; Morphologic artifacts ; Artifacts ; Health Care Costs ; Health Costs ; Healthcare Costs ; Catheters ; Injectable ; Silicates ; Thrombus ; Treatment Failure ; therapy failure ; Guidelines ; base ; crosslink ; cross-link ; Organ ; Procedures ; Peripheral ; Acute ; Chronic ; Clinical ; Phase ; Physiological ; Physiologic ; Ensure ; Failure ; radiologist ; Intellectual Property ; Immunological response ; host response ; immune system response ; immunoresponse ; Immune response ; fluid ; liquid ; Liquid substance ; Life ; mechanical ; Mechanics ; irritation ; meetings ; biocompatibility ; biomaterial compatibility ; Lytotoxicity ; cytotoxicity ; Performance ; success ; genotoxicity ; Hydrogels ; Toxicities ; Toxic effect ; sterile ; Sterility ; novel ; Devices ; carcinogenicity ; Modeling ; Property ; response ; Adverse effects ; Effectiveness ; Clotting ; Coagulation ; Coagulation Process ; Address ; Data ; in vivo ; in vivo Model ; Rodent Model ; Immunologics ; Immunochemical Immunologic ; Immunologic ; Immunological ; Immunologically ; Preparation ; Hindlimb ; Development ; developmental ; Image ; imaging ; cost ; Advanced Development ; design ; designing ; clinical efficacy ; Biodistribution ; Outcome ; cost effective ; migration ; innovation ; innovate ; innovative ; malformation ; Implant ; implantation ; usability ; high risk ; minimally invasive ; standard of care ; Sterilization ; Patient risk ; Formulation ; neurovascular ; neuro-vascular ; Traumatic injury ; clinical development ; phase 1 designs ; phase I designs ; hemocompatibility ; off-label use ; off-label application ; off-label prescribing ; porcine model ; pig model ; piglet model ; swine model ;
