Use of Diamond-Like Carbon Coatings to Reduce Leachables From Biomedical Metal Alloys and Polymeric Materials

美国食品药品监督管理局（FDA）要求制造商确保接触人体组织/体液的医疗器械或产品的安全性。因此，最大限度地减少医疗器械中化学物质（通常称为可降解物和可浸提物）的释放至关重要。这些物质的存在不仅可能是由于材料的化学成分，也可能是由于制造过程。医疗器械生物材料的沥滤物和浸提物可能对生物相容性产生重大影响，并可能对患者健康构成重大风险。该项目将最大限度地减少几类常见生物材料中可降解物质的释放，包括（a）聚氯乙烯（用于静脉内管和血液储存袋），（B）增材制造的聚醚醚酮（用于骨植入物）和（c）镍钛形状记忆合金（用于血管通畅性的心血管支架），通过在这些材料的表面上沉积氢化类金刚石（DLC）涂层。DLC是一种完全由碳原子组成的材料，它可以作为一种细胞友好的渗透屏障，防止可降解物质的释放。这种廉价的技术已被用于防止瓶装饮料工业中的氧气渗透。在医疗器械中使用的聚合物或金属合金上具有化学稳定性的DLC涂层将降低许多类别材料的可降解相关健康风险。该项目有三个目标。目标1：使用等离子体增强物理气相沉积在模型生物材料上沉积DLC涂层和涂层的物理化学表征。将使用扫描电子显微镜确认涂层中无针孔，确认涂层厚度，并评价表面形态。目标二：生理和最差情况条件下无涂层和DLC涂层生物材料的浸提物和可浸提物的化学表征和毒理学风险评定。该可交付成果的里程碑将是比较DLC涂层材料与无涂层材料的可浸提物和可挥发物释放。将进行毒理学危害识别评估，以确定任何材料是否构成毒理学风险。目的3：使用体外试验对涂层和未涂层/DLC涂层生物材料的浸提物/可浸提物进行生物相容性试验。未涂层和DLC涂层生物材料的浸提物和可浸提物将用于体外处理哺乳动物细胞，以评估细胞活力、活性氧（ROS）产生和促炎细胞标志物。目的是确认DLC涂层是否减少了医疗器械中常用生物材料的可浸提物/可降解物。如果该项目获得成功，医疗器械行业将拥有一种可应用于各种金属和聚合物的材料（DLC）。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The Food & Drug Administration (FDA) requires that manufacturers assure the safety of medical devices or products that contact body tissues/fluids. Therefore, it is vital to minimize the release of chemical species, commonly known as leachables and extractables, from medical devices. The presence of these species may be due not only to the chemical composition of the materials, but also from manufacturing processes. Leachables and extractables from medical device biomaterials may have a significant impact on biocompatibility and may pose significant risks to patient health. This project will minimize the release of leachables from several classes of common biomaterials, including (a) polyvinylchloride (used in intravenous tubing and blood storage bags), (b) additively manufactured polyetheretherketone (used in bone implants), and (c) nickel-titanium shape memory alloy (used in cardiovascular stents for vessel patency), by depositing hydrogenated diamond-like carbon (DLC) coatings on the surfaces of these materials. DLC is a material made up entirely of carbon atoms, it can serve as a cell-friendly permeation barrier that prevents the release of leachables. This inexpensive technology has been utilized to prevent oxygen permeation in the bottled beverage industry. A DLC coating that would be chemically-amenable on polymers or metal alloys used in medical devices would reduce leachable-associated health risks across many classes of materials.The project has three aims. Aim 1: Deposition of DLC coatings on model biomaterials using plasma enhanced physical vapor deposition and physico-chemical characterization of the coatings. Scanning electron microscopy will be used to confirm the absence of pinholes in the coating, to confirm the coating thickness, and to evaluate the surface morphology. Aim 2: Chemical characterization and toxicological risk assessment of extractables and leachables from uncoated and DLC-coated biomaterials under physiologic and worst-case conditions. The milestone for this deliverable will be a comparison of the release of extractables and leachables from the DLC coated materials compared to uncoated materials. A toxicologic hazard identification assessment will be conducted to determine if any of the materials pose a toxicological risk. Aim 3: Biocompatibility testing of extractables/leachables from coated and uncoated/DLC-coated biomaterials using in vitro assays. The extractables and leachables from both uncoated and DLC-coated biomaterials will be used to treat mammalian cells in vitro for assessment of cell viability, reactive oxygen species (ROS) production, and pro-inflammatory cell markers. The goal is to confirm if DLC coatings reduce extractables/leachables from biomaterials that are commonly used in medical devices. If the proposed project is successful, the medical device industry will have a material (DLC) for application to a wide variety of metals and polymers.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.