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

美国食品和药物管理局(FDA)要求制造商确保接触人体组织/液体的医疗设备或产品的安全性。因此，至关重要的是要最大限度地减少从医疗器械中释放的化学物质，即通常所说的可浸出物和萃取物。这些物种的存在可能不仅是由于材料的化学成分，也是由于制造过程。医疗器械生物材料中的可浸出物和可萃取物可能会对生物相容性产生重大影响，并可能对患者的健康构成重大风险。该项目将最大限度地减少几类常见生物材料的可浸出物的释放，这些材料包括：(A)聚氯乙烯(用于静脉导管和储血袋)，(B)添加制造的聚醚醚酮(用于骨植入)，以及(C)镍钛形状记忆合金(用于血管通畅的心血管支架)，方法是在这些材料的表面沉积氢化类金刚石碳(DLC)涂层。DLC是一种完全由碳原子组成的材料，它可以作为细胞友好的渗透屏障，防止可浸出物质的释放。这种廉价的技术已经被用来防止瓶装饮料行业的氧气渗透。在医疗设备中使用的聚合物或金属合金上可以化学修饰的DLC涂层将减少许多类别材料中与可浸出相关的健康风险。该项目有三个目标。目的1：利用等离子体增强物理气相沉积技术在模型生物材料表面制备类金刚石涂层，并对涂层的物理化学性能进行表征。扫描电子显微镜将用来确认涂层中没有针孔，确认涂层厚度，并评估表面形态。目的2：在生理和最坏情况下，对未包覆和DLC包覆的生物材料的萃取物和浸出物进行化学表征和毒理学风险评估。这一交付成果的里程碑将是将DLC涂层材料与未涂层材料的可提取物和可浸出物的释放进行比较。将进行毒理学危险识别评估，以确定是否有任何材料构成毒理学风险。目的3：采用体外生物相容性测试方法对包膜和未包膜/类金刚石包膜生物材料的可提取物/可浸出物进行生物相容性测试。未涂层和DLC涂层的生物材料的可提取物和可浸出物将用于在体外处理哺乳动物细胞，以评估细胞活力、活性氧物种(ROS)的产生和促炎细胞标记物。目标是确定DLC涂层是否减少了医疗器械中常用的生物材料中的可提取物/可浸出物。如果提议的项目成功，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智力优势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.