Novel honeycomb gallo-silicate microspheres for rapid hemostasis of oral and maxillofacial wounds

新型蜂窝状硅酸微球用于口腔颌面部伤口快速止血

• 批准号: 10378211
• 负责人: Isabelle L Denry
• 金额: $ 16.2万
• 依托单位: SIGMA CLERMONT
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10378211
• 关键词: Acute; Address; Aerobic; Alveolar periostitis; Amino Acids; Antibiotic Resistance; Area; Bacteria; Bacteriology; Biocompatible Materials; Biological Assay; Biometry; Blood Coagulation Disorders; Blood Platelets; Blood Vessels; Cells; Cellulose; Characteristics; Charge; Chemicals; Chemistry; Coagulation Process; Collagen; Complication; Development; Distal; Electrocoagulation; Emergency Situation; Ensure; Environment; Erythrocytes; Escherichia coli; Excision; Exhibits; Exposure to; Fibrin; Formulation; Gallium; Gelatin; Goals; Gram-Negative Bacteria; Hematology; Hemorrhage; Hemostatic Agents; Hemostatic function; Hospitals; Impaired healing; In Situ; In Vitro; Infection prevention; Ion Exchange; Ions; Laboratories; Link; Literature; Lithium; Microbiology; Microspheres; Military Personnel; Minimum Inhibitory Concentration measurement; Monitor; Natural regeneration; Oral; Oral Surgical Procedures; Outcome; Oxides; Particle Size; Pathway interactions; Patients; Plants; Platelet aggregation; Polysaccharides; Postoperative Hemorrhage; Pre-hospitalization care; Process; Production; Property; Protocols documentation; Pseudomonas aeruginosa; Regulation; Reporting; Research Personnel; Risk; Role; Saliva; Silicates; Site; Sodium; Staphylococcus aureus; Streptococcus; Streptococcus anginosus; Streptococcus mitis; Streptococcus pyogenes; Structure; Surface; Surgical Blood Loss; Surgical sutures; Testing; Thrombin; Thrombosis; Thrombus; Time; Tissue Preservation; Tissues; Topical Antibiotic; Tourniquets; Ursidae Family; Work; Zeolites; acute infection; aggregation factor; antimicrobial; antimicrobial drug; bacterial metabolism; base; biomaterial compatibility; chronic infection; clay; cost; innovation; maxillofacial; microbiota; multidisciplinary; novel; oral surgery specialty; pathogen; physical property; prevent; stem; success; three dimensional structure; viral transmission; wound; wound healing; zeta potential

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.

高度血管化的口腔和颌面部区域的出血不适合 通过放置止血带进行控制，并且通常需要使用局部止血剂 (THA)。 THA 通常用于控制严重出血，无论是军事还是民用 院前护理。对于接受手术的患者来说，控制止血的需要甚至更大 抗血栓治疗或患有出血性疾病。同时，口腔伤口和 提取部位暴露于唾液中丰富的微生物群落中，这可能会诱发急性或 慢性感染会延迟愈合，并且因抗生素耐药性的增加而变得复杂 物种。具有抗菌作用的 THA 可以预防这些并发症。我们的实验室 最近发现了一类新的高表面积蜂窝状硅酸盐微球框架 (SMF) 吸收剂可促进快速止血。在此发现的基础上，我们的长期目标是 使用蜂窝 SMF 开发速效局部止血剂和抗菌剂 与镓交换，进一步增强止血功效，确保抗菌 活动。外源供应的镓（以 Ga3+ 形式）的抗菌功效 细菌细胞依赖其替代 Fe3+ 的能力，从而扰乱细菌的新陈代谢。 同时，根据文献，我们假设报道的离子止血作用 镓依靠其絮凝纤维蛋白的能力。我们多学科团队在硅酸盐方面的专业知识 将利用化学、材料化学、血液学和微生物学来开发 镓交换 SMF（Ga-SMF）。该项目将从合成和 SMF 的表征（目标 1），包括其止血功效以及机制 通过它们促进止血。镓硅酸盐微球框架（Ga-SMF）将 通过离子交换产生（目标 2）。物理特性、镓释放曲线、生物相容性 将表征止血功效，以及镓离子增强止血功效的机制 将调查止血情况。最后，将针对一组测试抗菌功效 相关细菌。直接交付品是一种具有双重止血作用的新型抗菌 THA 作用，引发快速止血并预防感染，可以很好地应用 除了口腔颌面术后出血。