Infection resistant surface for ventricular assist device (VAD) transcutaneous dr

用于心室辅助装置 (VAD) 经皮手术的抗感染表面

• 批准号: 8892504
• 负责人: Patrick Thomas Cahalan
• 金额: $ 88.07万
• 依托单位: ENSION, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-16 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8892504
• 关键词: Acute; Adherence; Adhesions; Animal Model; Bacteria; Bacterial Adhesion; Blood; Blood Platelets; Body Surface; Caliber; Cannulas; Cell Count; Cells; Chemicals; Chronic; Cicatrix; Collagen; Complication; Confocal Microscopy; Control Groups; Coupling; Data; Detection; Development; Devices; Dimensions; Engineering; Environment; Evaluation; Family suidae; Fibrin; Fibroblasts; Fluorescence; Foreign-Body Reaction; Gentamicins; Healed; Health; Histocompatibility; Hydrogels; Immune; Immune response; Immune system; Immunofluorescence Microscopy; Implant; In Vitro; Infection; Inflammation; Inflammatory; Inorganic Sulfates; Label; Length; Leukocytes; Life; Measures; Medical Device; Methods; Microbe; Modeling; Monitor; Mus; Performance; Pharmaceutical Preparations; Phase; Polyurethanes; Process; Public Health; Research; Resistance; Resistance to infection; Silver; Skin; Solutions; Spatial Distribution; Structure of parenchyma of lung; Surface; Systemic infection; Testing; Tissue Sample; Tissues; Toxic effect; Treatment Step; Unspecified or Sulfate Ion Sulfates; antimicrobial; antimicrobial drug; base; biomaterial compatibility; commercialization; controlled release; design; fighting; healing; implant material; improved; in vitro testing; in vivo; inflammatory marker; innovation; man; medical implant; meetings; mouse model; prevent; prototype; response; ventricular assist device; von Willebrand Factor

DESCRIPTION (provided by applicant): Infection is a common and frequently very serious complication associated with medical implants. Man-made materials, including those used to fabricate ventricular assist devices (VADs), compromise the body's ability to fight infection in tw ways. First, by breaching skin with transcutaneous cannulae and drivelines, and second, by eliciting a foreign body reaction which results in scarring near the implant surface that creates an environment where bacteria can thrive outside the reach of the body's immune system. Currently available infection resistant materials typically rely on the release of antimicrobial substances. Though effective over the short-term, the released drugs can compromise normal healing and exacerbate the problem of isolating the implant surface from the body's immune defenses. Ension proposes development of an infection resistant surface designed to promote normal healing for application to the transcutaneous drivelines of ventricular assist devices. The proposed surface will incorporate a three-pronged approach to infection resistance; a low adhesion surface designed to prevent or hinder the attachment of microbes, controlled release of antimicrobial agents, and a natural collagen surface that promotes tissue integration. The innovation of the surface lies in going beyond the partial solution of acute antimicrobial release (such as the silver-impregnated gauze typically used in VAD transcutaneous driveline applications) to an engineered surface that also promotes optimal healing response of the adjacent tissue. The normal healing response near the surface generates tissue devoid of scarring and chronic inflammation, assuring a normal immune response and thus improving long-term infection resistance. Preliminary in vitro testing using prototype surfaces demonstrated that the proposed surface facilitates fibroblast adhesion (a part of normal healing), resists attachment of bacteria, and avoids causing toxicity that would hinder normal healing. The proposed Fast Track project will refine the most promising prototype surface and apply it to polyurethane substrate material (Phase I Specific Aim 1), fabricate and test implants treated with the optimized surface for biocompatibility in mice (Phase I Specific Aims 2 and 3), and perform detailed in vivo evaluation of infection resistance in pigs (Phase II). The Phase II in vivo testing will include groups of pigs implanted with bacterial challenge at implant, with periodic bacterial challenges following implant, and "unchallenged" controls (Phase II Specific Aim 2). Fluorescence labeling and confocal microscopy will be used to determine the types and numbers of cells at or near the implant surface and their spatial distribution (Phase II Specific Aim 3). These methods also allow detection of fibrin and collagen in the same tissue samples. The data obtained will be compared both to controls and to established data observed during normal healing. The surface is expected to show improvement over untreated controls with respect to healing response, bacterial adhesion, local infection and systemic signs of infection. Successful completion of the Fast Track project plan will result in a surface ready for qualification testing, regulatory approval, and subsequent commercialization.

描述（由申请人提供）：感染是与医疗植入物相关的常见且经常非常严重的并发症。人造材料，包括用于制造心室辅助设备（VAD）的材料，损害了人体以两种方式对抗感染的能力。首先，通过用经皮插管和驱动力突破皮肤，其次，引起异物反应，从而导致植入物表面附近的疤痕，从而创造了一个环境，在该环境中，细菌可以在人体免疫系统范围内繁殖。当前可用的抗感染材料通常依赖于抗菌物质的释放。尽管在短期内有效，但释放的药物可以损害正常的愈合，并加剧将植入物表面与人体免疫防御措施中隔离的问题。 Resion提出开发抗感染表面，旨在促进正常的愈合，以应用于心室辅助装置的经皮驱动力。所提出的表面将结合三方面的感染抗性方法。低粘附表面，旨在防止或阻碍微生物的附着，抗菌剂的受控释放以及促进组织整合的天然胶原蛋白表面。表面的创新在于超越了急性抗菌释放的部分溶液（例如，通常用于VAD经皮的传动系统应用中使用的银浸渍的纱布）到工程表面，该表面也促进了相邻组织的最佳愈合反应。表面附近的正常愈合反应会产生没有疤痕和慢性炎症的组织，从而确保正常的免疫反应，从而改善长期感染抗性。使用原型表面进行初步的体外测试表明，所提出的表面有助于成纤维细胞粘附（正常愈合的一部分），抵抗细菌的附着，并避免引起毒性，从而阻碍正常的愈合。拟议的快速轨道项目将完善最有前途的原型表面，并将其应用于聚氨酯底物材料（I阶段特异性目标1），制造和测试植入物，并用优化的表面治疗了小鼠的生物相容性（第I期特异性目标2和3），并在猪中对感染抗性的详细措施（II期II期）进行详细评估。 II期 体内测试将包括在植入物中植入细菌挑战的猪组，植入后具有周期性细菌挑战和“无挑战”的控制（II阶段特定的目标2）。荧光标记和共聚焦显微镜将用于确定植入物表面或其空间分布的细胞类型和数量（II期特异性目标3）。这些方法还允许在同一组织样品中检测纤维蛋白和胶原蛋白。获得的数据将与对照组和正常愈合期间观察到的已建立数据进行比较。对于愈合反应，细菌粘附，局部感染和全身感染迹象，表面对未处理的控制表现出改善。成功完成快速轨道项目计划将导致准备资格测试，监管批准和随后的商业化的表面。