State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P. R. China.
Joint Laboratory of Advanced Biomedical Materials (NFU-UGent), College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, P. R. China.
ACS Appl Mater Interfaces. 2021 Sep 29;13(38):45191-45200. doi: 10.1021/acsami.1c10747. Epub 2021 Sep 14.
Pathogenic biofilms formed on the surfaces of implantable medical devices and materials pose an urgent global healthcare problem. Although conventional antibacterial surfaces based on bacteria-repelling or bacteria-killing strategies can delay biofilm formation to some extent, they usually fail in long-term applications, and it remains challenging to eradicate recalcitrant biofilms once they are established and mature. From the viewpoint of microbiology, a promising strategy may be to target the middle stage of biofilm formation including the main biological processes involved in biofilm development. In this work, a dual-functional antibiofilm surface is developed based on copolymer brushes of 2-hydroxyethyl methacrylate (HEMA) and 3-(acrylamido)phenylboronic acid (APBA), with quercetin (Qe, a natural antibiofilm molecule) incorporated via acid-responsive boronate ester bonds. Due to the antifouling properties of the hydrophilic poly(HEMA) component, the resulting surface is able to suppress bacterial adhesion and aggregation in the early stages of contact. A few bacteria are eventually able to break through the protection of the anti-adhesion layer leading to bacterial colonization. In response to the resulting decrease in the pH of the microenvironment, the surface could then release Qe to interfere with the microbiological processes related to biofilm formation. Compared to bactericidal and anti-adhesive surfaces, this dual-functional surface showed significantly improved antibiofilm performance to prevent biofilm formation involving both Gram-negative and Gram-positive for up to 3 days. In addition, both the copolymer and Qe are negligibly cytotoxic, thereby avoiding possible harmful effects on adjacent normal cells and the risk of bacterial resistance. This dual-functional design approach addresses the different stages of biofilm formation, and (in accordance with the growth process of the biofilm) allows sequential activation of the functions without compromising the viability of adjacent normal cells. A simple and reliable solution may thus be provided to the problems associated with biofilms on surfaces in various biomedical applications.
在可植入医疗器械和材料表面形成的致病生物膜是一个紧迫的全球医疗保健问题。虽然基于细菌排斥或杀菌策略的传统抗菌表面在一定程度上可以延迟生物膜的形成，但它们在长期应用中通常会失效，而且一旦生物膜形成并成熟，就很难将其根除。从微生物学的角度来看，一种有前途的策略可能是针对生物膜形成的中期阶段，包括生物膜发展所涉及的主要生物学过程。在这项工作中，基于甲基丙烯酸羟乙酯（HEMA）和 3-（丙烯酰胺）苯硼酸（APBA）的共聚物刷开发了一种双功能抗生物膜表面，通过酸响应硼酸酯键将槲皮素（Qe，一种天然抗生物膜分子）掺入其中。由于亲水性聚（HEMA）组分的抗污性能，所得表面能够在接触的早期抑制细菌的粘附和聚集。一些细菌最终能够突破抗粘附层的保护，导致细菌定植。针对微环境中 pH 值的降低，表面可以释放 Qe 来干扰与生物膜形成相关的微生物过程。与杀菌和抗粘附表面相比，这种双功能表面在防止生物膜形成方面表现出明显改善的抗生物膜性能，可阻止长达 3 天的革兰氏阴性菌和革兰氏阳性菌的生物膜形成。此外，共聚物和 Qe 的细胞毒性可以忽略不计，从而避免了对相邻正常细胞的潜在有害影响和细菌耐药性的风险。这种双功能设计方法针对生物膜形成的不同阶段，并（根据生物膜的生长过程）允许在不损害相邻正常细胞活力的情况下顺序激活功能。因此，可能为各种生物医学应用中表面生物膜相关问题提供了一种简单可靠的解决方案。
