Development of biomaterials for hemorrhage control: a two-component approach




Pandya, Shaunak Girishkumarame

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Uncontrolled, non-compressible hemorrhage is a leading cause of death after trauma in the battlefield. Loss of blood along with resuscitation and hypothermia lead to coagulopathy which is characterized by low concentration of the blood clotting factors and a resultant inability of the body to achieve natural coagulation. Currently available hemostatic agents are either local or systemic in nature. The majority of externally applied agents aid in hemostasis by physical means (water absorption and scaffolding) and rely on the natural clotting cascade for hemostasis. Currently pursued systemic hemostatic agents are mainly recombinant clotting factors which are aimed at augmenting the clotting cascade to induce coagulation; however, they are costly, susceptible to degradation and pose a risk of disease transmission. An injectable biomaterial based approach might provide a more controlled and cost effective alternative; however, there have been very few attempts at designing of such an injectable biomaterial. For example, Arg-Gly-Asp (RGD) modified poly (dl-lactide-co-glycolide) (PLGA) nanoparticles that mimic platelets have been shown to target internal hemorrhages. However, such an independent system would require a large quantity of the material to be administered. Thus, currently existing systems are still not optimal for use in battlefield and there is a need for newer agents, which are cost effective, efficient in low quantities, work independently of the clotting cascade, and provide more control over hemostasis. Here, we aimed to develop a novel hemostasis system composed of both an injected and an external component, which can achieve hemostasis by reacting at the wound site and actively involving blood cells in the clot. Biotin avidin chemistry was used as a model system for two-component fabrication. Semisynthetic pegylated phospholipids were identified as ideal cell surface modification agents. Phosphoethanolamine with 18C lipid tail and 2000 Da PEG unit was found to be most efficient. Pharmacodynamics and pharmacokinetics studies included investigation of effective concentration, incubation period, binding strength, membrane stability, and effect on other mammalian cells. Water soluble polymer carboxymethyl chitosan was modified using biotin and avidin to fabricate the external component. The two-component system was found to be effective in increasing overall clot strength proving the central hypothesis. Therefore, we have successfully demonstrated an alternative to current single component hemostatic system with a potential to improve hemorrhage control.


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Biomaterials, Chitosan, Coagulation, Hemorrhage, Hemostat, Hydrogel



Biomedical Engineering