Hemorrhages in the highly vascularized oral and maxillofacial region are not amenable to control by tourniquet placement and often require the use of Topical Hemostatic Agents (THAs). THAs are commonly used to control severe bleeding, this is the case in both military and civilian pre-hospital care. The need for controlling hemostasis is even greater in patients undergoing antithrombotic therapy or suffering from bleeding disorders. Meanwhile, oral wounds and extraction sites are exposed to the rich microflora present in saliva, which can induce acute or chronic infections that delay healing, and are complicated by the rise of antibiotic-resistant species. THAs that are also antimicrobial would prevent these complications. Our laboratory recently discovered a new class of high surface area, honeycomb silicate microsphere framework (SMF) absorbents that prompt rapid hemostasis. Building on this discovery, our long-term goal is to develop fast-action, topical hemostatic and antimicrobial agents using honeycomb SMFs exchanged with gallium, which will further strengthen hemostatic efficacy and ensure antimicrobial activity. The antimicrobial efficacy of exogenously supplied gallium (in the form of Ga3+) to bacterial cells relies on its ability to replace Fe3+, thereby perturbing bacterial metabolism. Concurrently, based on the literature, we hypothesize that the reported hemostatic action of ionic gallium relies on its ability to flocculate fibrin. The expertise of our multidisciplinary team in silicate chemistry, materials chemistry, hematology, and microbiology will be leveraged to develop gallium-exchanged SMFs (Ga-SMFs). The project will initiate with the synthesis and characterization of SMFs (Aim 1), including their hemostatic efficacy as well as the mechanisms by which they promote hemostasis. Gallo-silicate microsphere frameworks (Ga-SMFs) will be produced by ion-exchange (Aim 2). Physical properties, gallium release profiles, biocompatibility and hemostatic efficacy will be characterized, and mechanisms by which gallium ion enhances hemostasis will be investigated. Finally, the antimicrobial efficacy will be tested against a panel of relevant bacteria. Direct deliverables are a new class of antimicrobial THAs with dual hemostatic action, triggering rapid hemostasis and preventing infections, that could bear applications well beyond oral and maxillofacial post-surgical hemorrhages.
This multidisciplinary project assembles a team of researchers with expertise in biomaterials, chemistry, microbiology, hematology, maxillofacial surgery and biostatistics to develop antimicrobial topical hemostatic agents based on innovative honeycomb silicate microsphere frameworks that are highly absorbent. Topical hemostatic agents are in high demand in pre-hospital emergency situations and their use has also increased for hemorrhage control in patients undergoing antithrombotic treatment and with compromised hemostasis. Success with the specific goals of this application will enable us to offer a new class of synthetic topical hemostatic and antimicrobial agents that are fast-acting and prevent infections at the wound site, while preserving tissue integrity.
