Investigating a Flexible, Degradable, Local Antimicrobial Delivery System

研究灵活、可降解的局部抗菌传递系统

基本信息

批准号：
8885285
负责人：
Warren Oliver Haggard
金额：
$ 28.83万
依托单位：
UNIVERSITY OF MEMPHIS
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-03-10 至 2019-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8885285
关键词：
Address Adhesions Adhesives Adverse effects Amikacin Animal Model Antibiotic Therapy Antibiotics Area Bacteria Bacterial Infections Biocompatible Biocompatible Materials Biological Assay Biopolymers Bone Injury Bone Regeneration Bone Transplantation Calcium Sulfate Chitosan Clinical Closed Fractures Complex Debridement Defect Devices Drug Formulations Effectiveness Elements Engineering Evaluation Event Exhibits Focal Infection Fracture Gel Health Care Costs Implant In Vitro Incidence Infection Infection prevention Injectable Injury Investigation Kinetics Knee Lead Length Measures Metals Methods Microbial Biofilms Modeling Modification Morbidity - disease rate Mus Musculoskeletal Open Fractures Operative Surgical Procedures Orthopedic Procedures Orthopedics Oryctolagus cuniculus Outcome Paste substance Patients Pharmaceutical Preparations Polymethyl Methacrylate Porifera Preventive Procedures Pseudomonas aeruginosa Quality of life Rattus Regimen Reporting Research Shapes Site Skeletal system Skin Tissue Soft Tissue Injuries Solid Staphylococcus aureus System Testing Therapeutic Time Tissues Trauma Treatment Cost Treatment Efficacy Treatment outcome Vancomycin Water analog antimicrobial bactericide biomaterial compatibility bone cost flexibility improved in vivo injured innovation meetings microorganism musculoskeletal injury novel pathogen physical property point of care pre-clinical prevent public health relevance repaired research study sample fixation soft tissue wound

项目摘要

DESCRIPTION (provided by applicant): Numerous events can lead to bacterial infections of the skeletal system, including musculoskeletal injuries, especially open fractures and orthopaedic procedures, such as implants or bone grafts. Open fractures (associated with overlying skin and soft tissue injuries) often result in exposure of injured tissue and fractured bone to contaminating microorganisms, leading to infection more often than closed fractures. Surgical procedures, especially those involving implants or bone grafts, expose these same tissues to contamination. Bacterial contamination is often further complicated by compromised local vasculature and formation of bacterial biofilm in wound tissues and in the devices used for stabilization and post-surgical repair. All of these factors can contribute to severe negative treatment outcomes, including increased morbidity, extended length of treatment, and higher cost. Degradable and non-degradable local antibiotic delivery systems are often used to supplement traditional regimens of systemic antibiotic administration and surgical debridement. While these systems can achieve high concentrations of antibiotics at the injury site, each has associated problems such as poor degradability, incomplete site coverage, or inadequate release profiles. To address the critical need for improved methods of targeted antimicrobial delivery, we will build on our previous research to develop and test an injectable paste with sponge aggregates, using a degradable composite material derived from the natural biomaterial chitosan. This tunable composite paste will be engineered to deliver point-of-care, clinician-selected antibiotics and to provide full coverage in complex wound areas and irregularly shaped biomaterials, e.g., fixation devices. We hypothesize that the injectable, antibiotic-loaded chitosan composite paste will locally deliver levels of antibiotics that effectively eliminate contaminating microorganisms and prevent biofilm formation in traumatic wounds. After in vitro evaluations of elution, degradation, bactericidal, and anti-biofilm and physical properties of the paste and a preliminary animal model in vivo biocompatibility study, two established infected animal models with increasing complexity will be used to functionally assess the paste composite with antibiotics (selected for Gram + and Gram - coverage. The new composite paste system will also be compared to the traditional local delivery systems, polymethyl-methacrylate beads and calcium sulfate. We will tailor our tunable and degradable composite paste delivery system to meet clinical needs for preventing infections in complex musculoskeletal trauma.

描述（通过应用证明）：许多事件会导致骨骼系统的细菌感染，而骨质裂缝和骨科手术（例如植入物或骨移植物）通常会导致骨骼组织和骨骼骨折以污染微生物相同的组织将局部污染物削弱，并在伤口组织中形成液体生物膜以及用于稳定的设备，并在外科手术后造成严重的负面治疗结果。。复合糊剂将被启动，以提供临床医生选择的抗生素，并在复杂的伤口区域和不规则的shaom大疗法中提供全部覆盖范围，例如，我们假设可注射的，抗生素的壳聚糖壳聚糖奇质奇体奇体奇质式搭配装置在局部提供抗生素水平，可消除创伤性伤口中的生物膜形成，降解，杀菌和anti-biofilm和静脉动物模型的物理特性抗生素也将与传统的局部系统，多甲基 - 甲基丙烯酸酯珠和硫酸钙进行比较。