Center for Convergence Bioceramic Materials, Korea Institute of Ceramic Engineering and Technology, 202, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, South Korea; Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea.
Center for Convergence Bioceramic Materials, Korea Institute of Ceramic Engineering and Technology, 202, Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, South Korea.
Acta Biomater. 2021 Apr 15;125:242-252. doi: 10.1016/j.actbio.2021.02.038. Epub 2021 Feb 28.
Bacterial infections and the formation of biofilms on the surface of implantable medical devices are critical issues that cause device failure. Implantable medical devices, such as drug delivery technologies, offer promising benefits for targeted and prolonged drug release, but a number of common disadvantages arise that include inadequate release and side effects. Organic film coatings for antifouling and drug delivery are expected to overcome these challenges. Ferrocene polymer-based multifunctional multilayer films were prepared to control the reactive oxygen species (ROS)-responsive release of therapeutic agents while maintaining an antifouling effect and improving biocompatibility. Polymers based on ferrocene and polyethylene glycol were prepared by controlling the molar ratio of carboxylate and amine groups. Layer-by-layer deposition was optimized to achieve the linear growth and self-assembly of dense and stable films. Outstanding anti-biofilm activity (~91% decrease) could be achieved and the films were found to be blood compatible. Importantly, the films effectively incorporated hydrophobic drugs and exhibited dual-responsive drug release at low pH and under ROS conditions at physiological pH. Drug delivery to MCF-7 breast cancer cells was achieved using a Paclitaxel loaded film, which exhibited an anticancer efficacy of 62%. STATEMENT OF SIGNIFICANCE: Healthcare associated infection is caused by the formation of a biofilm by bacteria on the surface of a medical device. In order to solve this, extensive research has been conducted on many coating technologies. Also, a method of chemical treatment by releasing the drug when it enters the body by loading the drug into the coating film is being studied. However, there is still a lack of technology that can achieve both functions of preventing biofilm production and drug delivery. Therefore, in this study, a multilayer thin film that supports drug and inhibits biofilm formation was prepared through Layer-by-Layer coating of a polymer containing PEG to prevent adsorption. As such, it helps the design of multifunctional coatings for implantable medical devices.
细菌感染和植入式医疗器械表面生物膜的形成是导致器械失效的关键问题。植入式医疗器械，如药物输送技术，为靶向和延长药物释放提供了有前景的益处，但也出现了一些常见的缺点，包括释放不足和副作用。用于防污和药物输送的有机薄膜涂层有望克服这些挑战。制备了基于二茂铁聚合物的多功能多层膜，以控制活性氧（ROS）响应型治疗剂的释放，同时保持抗污效果并提高生物相容性。通过控制羧酸根和胺基的摩尔比制备了基于二茂铁和聚乙二醇的聚合物。通过优化层层沉积来实现致密和稳定膜的线性生长和自组装。可以实现出色的抗生物膜活性（降低约 91%），并且发现该膜具有血液相容性。重要的是，该膜可以有效掺入疏水性药物，并在低 pH 和生理 pH 下的 ROS 条件下表现出双重响应性药物释放。使用负载紫杉醇的膜实现了 MCF-7 乳腺癌细胞的药物输送，其抗癌功效为 62%。 意义声明：与医疗保健相关的感染是由细菌在医疗器械表面形成生物膜引起的。为了解决这个问题，已经对许多涂层技术进行了广泛的研究。此外，还通过将药物加载到涂层膜中来研究通过进入体内时释放药物的化学处理方法。然而，仍然缺乏能够同时实现防止生物膜产生和药物输送的功能的技术。因此，在这项研究中，通过聚乙二醇（PEG）的聚合物的层层涂层制备了支持药物和抑制生物膜形成的多层薄膜，以防止吸附。因此，它有助于设计用于植入式医疗器械的多功能涂层。
