Arsenal foam system for acute hemorrhage Julia Donner & David Deckey Biomaterials Julia

Notable quotation Senior author David King, MD, a trauma surgeon at Massachusetts General Hospital with significant combat theater experience said: "Currently, there are no effective pre-hospital treatments available for intra- abdominal bleeding on the battlefield. Our ultimate goal is to find innovative ways to improve treatment and save lives of those who are serving their country, as well as those who experience serious injury through trauma." Julia

Clinical Problem: Non compressible Hemorrhage Non-compressible bleeding accounts for 85% of preventable deaths Abdominal hemorrhage involves injury to the spleen, liver, or retroperitoneal vasculature Abdominal hemorrhage cannot be treated with tourniquets or topical dressings harder to treat and stop early on Injury often occurs far from treatment facilities Designed for soldiers who have sustained severe abdominal trauma Control intra-abdominal bleeding during transport to hospital/health care facility Julia Non-compressible bleeding accounts for 85% of preventable deaths 80% of which include acute hemorrhage within the abdomen/torso Injury often occurs far from treatment facilities Transport time is too long Designed for soldiers who have sustained severe abdominal trauma i.e. gunshot wounds, shrapnel injuries

Current standard of care Pressure Dressings/Gauze transport Gauze recommended by the Committee on Tactical Combat Casualty Care is that Combat Gauze™ (Z-Medica) Current hemostatic dressing of choice and every soldier carries this dressing in their first aid kit Followed by emergency surgical intervention Julia

Bridging the Gap: New technology DARPA: Defense Advanced Research Projects Agency 2010 Wound Stasis Program Designed for US Military injured in battle “Golden Hour” Arsenal Medical Inc. designed biomaterial Dave In 2010, DARPA launched its Wound Stasis System program with the objective of finding a technology solution to address trauma-induced internal hemorrhage. The program sought to identify a biological mechanism capable of discriminating between injured and healthy tissue and binding preferentially to the wounded tissue. The Department of Defense has a goal to provide wounded soldiers with advance-level treatment within 60 minutes of being wounded. This 60 minute time frame, known as the “Golden Hour” is critical in helping a soldier survive an injury.

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Expanded foam in intra-abdominal cavity How does it work? It is injected into the intra-abdominal cavity Surrounds bleeding and forms around injured organs Controls hemorrhage Dave Within about one minute after a medic inserts the liquids at the midline—near the belly button—the mixture expands to nearly 30 times its original volume and then turns solid. It slows or halts hemorrhaging by sealing wounded tissues. Once the patient can get to intensive care, doctors would remove the solid mass in under ONE MINUTE Expanded foam in intra-abdominal cavity

Phases of development & Funding Phase I pre-clinical, proof-of-concept work was a success Award of $15.5M for late-stage development Did pre-clinical trials on pigs Results presented at the 2012 American Association for the Surgery of Trauma Annual Meeting Currently in Phase II contract from DARPA Current total funding: $22.5 M The Arsenal Foam Technology is currently not available for sale or distribution and is limited to clinical investigational use only. Dave

Finding the perfect foam Analyzed 1,200 foams Only one was perfect Perfect expansion Right viscosity Hydrophobic a) Ventral surface b) Dorsal surface c) Dissected foam Arrows indicate injury site and blood clot formation Julia

About the FOAM Foam is made of two liquid phases: polyol & isocyanate Create self-expanding, hemostatic poly(urethane urea) foam Polyol: oil-based, flexible polymer Isocyanates: highly reactive, low molecular weight and widely used to create flexible/rigid foams, fibers, coatings… Combination has been previously used to make mattresses, foam insulation for appliances, home and automotive seats, spandex, and adhesives Julia

Arsenal foam properties Conformal contact with injured tissue in presence of severe bleeding Ability to tamponade bleeding vessels without visualization Minimally invasive delivery of liquid-state foam through low-profile system Biocompatible materials Easy to remove later by surgeon Julia Scanning electron micrograph

Does it work? High grade hepato-portal injury were created in pigs resulting in non- compressible internal bleeding. Experimental & control treatments were introduced Control: battlefield fluid resuscitation Experimental: Foam injection Used at minimally invasive level- Reduces blood loss by 85% Dave swine as subjects, researchers induced liver injury by wrapping a wire around the organ during surgery, closing the animal then pulling on a portion of the wire that had been left protruding through the skin. waited 10 minutes between pulling the wire and injecting the two liquids in order to allow the blood to pool inside the body, as it often does in combat wounds.

Results Survival rates measured over 3 hour trial period Control group saw only 3% survival rate Mean Survival time 43±50 mins. Experimental group saw 72% survival rate Mean survival time 154±48 mins. Dave The foam reduced blood loss six-fold in those tests three hours after the injury the survival rate was 72 percent in the treatment group versus only 8 percent in the control group. Swine are often used as test subjects because pigs have an organ structure very similar to humans.

Possible complications Hemorrhage and bleeding out causing death Internal bruising Metabolic consequences of chemical reaction Possible allergic reaction to material in foam Residual Foam after removal Dave After the material solidifies, it can cause bruising. the reaction between the two liquids generates heat, which raises the temperature of surrounding tissue by about 2 or 3 degrees Celsius. temperature increase is on par with a high-grade fever. Some patients might also have an allergic reaction to the foam. Pieces of solidified foam could break off inside the body and become EMBOLI, eventually blocking blood flow to the legs or lungs.

Future implications Potential to aid civilians who sustain abdominal trauma Examples: Car accident injuries Falls Sporting events Gunshot wounds (not military related) Other abdominal trauma far from hospitals Julia

Notable quotation James Barry, PhD, Executive Vice President and Chief Operating Officer of Arsenal "The team of engineers and scientists at Arsenal Medical is excited to be working on one of the most difficult challenges in battlefield medicine . There can be no more important goal for all of us who work in healthcare than to save lives. And working to help save the lives of our soldiers is exceptionally motivating." Leave open as we finish