**1. Introduction**

Polyurethane (PU) ureteral stents are wildly used in urological clinics for their good flexibility and elasticity, biocompatibility, and low cost compared to what or within which range of materials [1,2]. However, the hydrophobic surface of PU reduces the antifouling and antimicrobial properties, which results in the increasing amount of protein adsorption, bacteria adhesion, and salt deposition in a urine environment [3,4]. Thus, encrustation, infection, and implant-related post-complications such as ureteral stricture, perforation, and mucosal injury [5,6] are observed during the implantation in vivo. Thus, the antimicrobial property of the stent's surface is vital for its service life in clinic. It is believed that an ideal antibacterial surface possesses properties of repelling protein adsorption in order to prevent initial bacteria attachment [7,8], repelling direct bacteria adhesion and killing the attached bacteria during the period of implantation in human body. With the aim of achieving these targets, various materials are applied to modify the PU surface to improve its hydrophilicity or to confer its antibacterial properties. Yuan et al. [9] modified chondroitin sulfate onto the PU surface to improve its hydrophilicity and reduce the protein adsorption. Manohar et al. [4] covalently crosslinked papain onto PU to prevent bacterial adhesion. Fischer et al. [10] attached a hydrogel coating loaded with Ag nanoparticles to

**Citation:** Yuan, H.; Xue, C.; Zhu, J.; Yang, Z.; Lan, M. Preparation and Antifouling Property of Polyurethane Film Modified by PHMG and HA Using Layer-by-Layer Assembly. *Polymers* **2021**, *13*, 934. https:// doi.org/10.3390/polym13060934

Academic Editor: José Miguel Ferri

Received: 26 February 2021 Accepted: 14 March 2021 Published: 18 March 2021

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a PU conduit to improve its antibacterial activity. However most material modifications can only improve one aspect of performance of the surface. Therefore, modification with an antibacterial agent and antifouling material on the surface is a good strategy to endow the PU surface with both antifouling properties and bactericidal properties [11,12], which would be a desirable antibacterial surface for clinical usage.

A surface with good hydrophilicity has been proven to effectively prevent non-specific protein adsorption. Hyaluronic acid (HA) is one of the most hydrophilic molecules in nature with non-toxic, non-immunogenic, non-inflammatory, and biodegradable properties [13–16]. HA is also a polyanion glycosaminoglycan that can repel most negativelycharged proteins and bacteria with negatively-charged cell membranes by electrostatic repulsive force. Conversely, it would be able to electrostatically attract cationic antimicrobial such as chitosan [17,18], quaternary ammonium salts [19,20], and cationic antimicrobial peptides [21] to integrate antibacterial function. Hence, HA is suitable for the surface modification of materials to reach the ultimate purpose of reducing bacterial adhesion [11,22]. Polyhexamethylene guanidine (PHMG) is a highly water-soluble, colorless, and odorless positively-charged antimicrobial [23]. Due to its broad spectrum activity against bacteria and fungi [24,25] and its low toxicity to mammals [26], PHMG has been successfully applied in several products such as topical wound solutions, contact lens cleaning products, and cosmetics [26–28]. Wei et al. [29] demonstrated that aqueous solutions of PHMG with concentrations as low as 1.0 ppm showed more than a 90.0% antibacterial rate. Ding et al. [30] bonded PHMG to resins to generate antibacterial acrylic coatings. The inhibitory factors against both *Escherichia coli* (*E. coli*) and *Staphylococcus aureus* (*S. aureus*) were over 99.99% at a PHMG content of 1.0 wt%. Therefore, the combination of HA and PHMG provides the modified surface with the desirable multifunction of hydrophilicity and antibacterial activity.

In this study, we created PHMG/HA multilayer films on PU by using layer-by-layer self-assembly with HA and PHMG as polyanions and polycations to render the surface of PU films with both antifouling and antibacterial properties. PHMG was chemically bonded to the PU surface via the reaction between amide groups of PHMG and isocyanato groups modified on PU films. Negatively-charged HA was assembled by electrostatic adsorption with positively-charged PHMG modified on PU films. Simultaneously, HA and PHMG were also covalently combined by the reaction of the partial activated carboxyl group of HA and amide groups of PHMG. The different concentrations of HA and PHMG as well as and the number of assembled layers were studied to attain PU-(PHMG/HA)<sup>n</sup> films with different properties. The surface properties of modified and unmodified PU films were characterized by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), water contact angle (WCA), and atomic force microscopy (AFM). The antifouling and antibacterial properties of the surface were detected by a bicinchoninic acid (BCA) protein detection kit and bacterial assay. Finally, the cytotoxicity of L929 cells was estimated for the improvement in the biocompatibility of the material.
