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

基本信息

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
项目类别：
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

项目摘要

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区系，这可能会诱发急性或慢性感染会延迟愈合，并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之外。