Investigating a Flexible, Degradable, Local Antimicrobial Delivery System

研究灵活、可降解的局部抗菌传递系统

• 批准号: 9032448
• 负责人: Warren Oliver Haggard
• 金额: $ 31.52万
• 依托单位: UNIVERSITY OF MEMPHIS
• 依托单位国家: 美国
• 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/9032448
• 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; Effectiveness; Elements; Engineering; Evaluation; Event; Exhibits; Focal Infection; Formulation; Fracture; Gel; Health; 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; improved outcome; in vivo; injured; innovation; meetings; microorganism; musculoskeletal injury; novel; pathogen; physical property; point of care; pre-clinical; prevent; repaired; research study; sample fixation; soft tissue; wound

 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（由申请人提供）：许多事件都可能导致骨骼系统的细菌感染，包括肌肉骨骼损伤，尤其是开放性骨折和骨科手术，例如植入物或骨移植物（与覆盖的皮肤和软组织损伤相关）。导致受伤的组织和骨折的骨头暴露于污染微生物，比闭合性骨折更容易导致感染，尤其是涉及植入物或骨头的手术。局部血管系统受损以及伤口组织和用于稳定和术后修复的装置中细菌生物膜的形成往往使细菌污染变得更加复杂。所有这些因素都可能导致严重的负面治疗。可降解和不可降解的局部抗生素输送系统通常用于补充传统的全身抗生素给药和手术清创方案。可以在损伤部位实现高浓度的抗生素，但每种方法都存在相关问题，例如降解性差、部位覆盖不完整或释放曲线不充分。为了满足改进靶向抗菌药物递送方法的迫切需求，我们将在之前的研究基础上使用源自天然生物材料壳聚糖的可降解复合材料，开发并测试一种可注射的海绵聚集体糊剂。这种可调节的复合糊剂将被设计用于提供临床医生选择的即时护理抗生素，并提供全面覆盖。在体外洗脱评估后，我们发现，可注射的、负载抗生素的壳聚糖复合糊剂将有效消除污染微生物并防止创伤性伤口中生物膜的形成。糊剂的降解、杀菌、抗生物膜和物理特性以及初步的动物模型体内生物相容性研究，两个已建立的复杂性不断增加的感染动物模型将用于功能评估与抗生素的复合糊剂（选择革兰氏+和革兰氏-覆盖率）。新的复合糊剂系统还将与传统的局部输送系统、聚甲基丙烯酸甲酯珠和硫酸钙进行比较。我们将定制我们的可调谐和可降解的复合糊剂输送系统满足预防复杂肌肉骨骼创伤感染的临床需求。