Lampe Distinguished Professor North Carolina State University and University of North Carolina at Chapel Hill Raleigh, North Carolina, United States
Introduction: : Bleeding after trauma leads to numerous potentially survivable deaths in both military and civilian patients. Particularly in rural and austere environments, it is difficult to transport natural blood products to treat bleeding in the pre-hospital setting. Additionally, natural blood products have non-ideal storage requirements and blood shortages are common. To address this issue, we have developed a synthetic platelet platform comprised of a pNIPAm microgel core conjugated to a fibrin-specific antibody fragment. This technology, termed SymClot, is similar in size, shape and morphology as activated platelets. The fibrin-binding ability of the particles mimics the function of GPIIb-IIIa-mediated binding of platelets and facilitates particle mediated crosslinking of fibrin fibers to accelerate clot formation. Due to the high deformability of the SymClot microgel core, along with the fibrin-binding action, SymClot is able to induce clot retraction which enhances clot stability and promotes tissue repair.
Materials and
Methods: : The ability of SymClot to promote hemostasis after trauma has been explored in several rodent trauma models including models of arterial and venous injury, and in both rodent and porcine liver laceration injury models. Biodistribution and safety have also been evaluated in these models. Recent studies have begun to explore the action of SymClot in rodent models of polytrauma combining arterial injury with traumatic brain injury.
Results, Conclusions, and Discussions:: SymClot has been found to enhance clot formation after trauma in arterial and venous rodent injury models. Following liver lacerations in either rodents or pigs, SymClot is able to significantly decrease bleeding times and facilitate healing of injured tissue when administered prophylactically or immediately after injury. SymClot was found to be cleared renally within an hour after intravenous administration. Pilot studies in a polytrauma model indicate that administration of SymClot after controlled cortical impact and femoral artery injury decreases lung infection three days after injury, indicating that SymClot may modulate inflammatory responses. Overall, these preclinical studies demonstrate the utility of SymClot as an alternative to natural blood products after trauma.
