Superior anti-biofouling properties of mPEG-modified polyurethane networks via incorporation of a hydrophobic dangling chain

Highlights

• Enhanced polyethylene glycol surface content improved anti-biofouling properties.

• Hydrophobic dangling chains act as surface directing groups for hydrophilic moieties.

• A polyurethane coating with stimuli-responsive surface under wet/dry conditions

• Low-water-uptake and superior hydrophilic polyurethane network

Abstract

PEG-modification is a proven method to enhance the hydrophilicity, protein resistance, and anti-biofouling properties of polymer coatings. It is considered as the gold standard interfacial modification technique such that the higher PEG content, the higher hydrophilicity, and lower protein adsorption, i.e., the initial stage of the biofouling process. Nevertheless, increasing the PEG content causes a higher water uptake, which declines the polymer mechanical strength and increases its hydrolytic degradation rate. Thus, an effective strategy to produce a limited-water-absorbing PEG-modified polymer is to force the majority of PEG molecules to migrate towards the interfacial region while the modification takes place. In the current paper, we report the synthesis and characterization of crosslinked polycarbonate-based polyurethanes (PU) containing methoxy polyethylene glycol (mPEG) dangling chains. We show that the simultaneous incorporation of a limited amount of a low-surface-energy dangling chain, i.e., 1-octadecanol (oDEC), along with mPEG, results in a considerably higher mPEG surface concentration, according to X-ray photoelectron spectroscopy (XPS), and a significantly lower water contact angle (WCA), up to 45° lower. We also put forward a reasonable mechanism for our outstanding observation and verified it through extensive experiments, e.g., dynamic WCA, Atomic force microscopy (AFM), and XPS. Moreover, we outline a delicate dynamic WCA experimental protocol, by which the smart and responsive behavior of our coatings is illustrated. Eventually, we examined the mixed hydrophobic/hydrophilic dangling chains strategy for low-protein adsorption applications, in which a great potential has been discovered.

Introduction

Materials interfaces are always prone to the adsorption of molecules, proteins, cells, and microorganisms. Bio-fouling is a phenomenon caused by biomolecules accumulation on surfaces and since it is mediated by proteins, inhibition of protein adsorption can effectively prevent the biofouling process [[1], [2], [3]]. It poses serious problems in the medical applications: protein adsorption at the interface with the biological environment can reduce the sensitivity of diagnostic devices, causes inflammation, and clot formation in the host [4,5]. High protein adsorption is often associated with surface hydrophobicity [6], which is the surface characteristic of the majority of polymer materials. Therefore, employing hydrophilic agents as the surface-modifying additives is a key strategy to reduce protein adsorption. Among them, PEG derivatives prevent the initial adhesion of proteins and cells to the surface due to establishing a highly stable hydration layer [[7], [8], [9]]. This layer works as a physical and an energetic barrier to resist protein adsorption [10]. Thus, PEG derivatives are widely considered as a gold standard among the protein-resistant additives in biomedical applications, e.g., contact lenses [11], cardiovascular [12], and adhesives in health care [13]. Nevertheless, high water swelling of PEG-modified coatings causes low stability and reduces the mechanical strength [14,15]. One possible solution is to accompany the PEG derivatives with a hydrophobic material, which results in an amphiphilic system that regulates the surface interactions, and controls the water uptake [3,8].

Amphiphilic coatings often exhibit a smart response to the environment due to the simultaneous dual chemical nature of hydrophobic and hydrophilic components. They can switch their surface properties from hydrophobic to hydrophilic in contact with polar environments like water [16]. Such smart polymeric surfaces can reorganize or reorient themselves repetitively at the interface as the interacting environment changes. Moreover, the simultaneous presence of the hydrophilic and hydrophobic segments at the interface increases the resistance to protein adsorption and facilitates the removal of adsorbed proteins, respectively [17].

To date, several approaches have been adopted to prepare amphiphilic protein-resistant polymer coatings. One of the most widely used routes to form an amphiphilic surface is the functional modification of pre-synthesized polymers. Although various hydrophobic segments, including saturated hydrocarbons [18], silicone-based [19], and fluorinated [20] materials, were used, PEG oligomers have been the unraveled hydrophilic segment [[21], [22], [23], [24]]. A particularly useful amphiphilic composition consists of side groups prepared from short PEG and straight-chain hydrocarbons, available as the Brij™ series of non-ionic surfactants [18,25]. Hydrocarbon-based amphiphilic materials have negligible environmental problems as compared to the fluorinated ones [26], while they are almost as effective [18,24,25]. Note that the protein resistance performance of Brij-modified copolymers shown to be enhanced by increasing the length or amount of PEG (hydrophilic) segment [24,25]. Another type of amphiphilic surfaces is based on the crosslinked PDMS films containing PDMS and PEGylated-fluoroalkyl blocks [27,28]. In another well-known approach, copolymers containing side chains are physically dispersed in an elastomeric matrix, where there is no covalent bond between the components [3]. There, the high flexibility of the (physically) mixed components enhances the protein-rejection ability; however, the possible leaching of added components affects the coatings interfacial properties in time [29]. One way to overcome this problem is to use tethered dangling chains, i.e., a component with one reactive group that chemically bonds to the polymer matrix [30]. There, the free (non-reactive) side of the dangling chain provides extra flexibility for the protein repellant chemical moieties, which is somehow as effective as the hydrophilicity of the dangling chains [31].

PU matrices are ideal basements for attaching various dangling chains for biomedical applications due to two main reasons: great biocompatibility of PUs and easy availability of the reactive groups. However, PU based coatings with PEG-containing dangling chains as protein-repellant coatings have been scarcely studied. Among them, Galhenage et al. [32] showed that a longer PEG chain might be more effective in fouling release behavior of siloxane–polyurethane coatings. Vaidya and Chaudhury [33] and Tan et al. [34] synthesized a PEG–containing amphiphilic segmented polyurethane and showed that the hydrophobic segments drag the hydrophilic PEG groups close to the surface (most likely in the subsurface region). This result has been reaffirmed in other studies as well [17,35]. Also, fibrinogen adsorption and platelet deposition on the PEG-based PUs were significantly reduced compared to the unmodified ones [34]. Liu et al. [36] concluded that grafting PEG onto the surface of aliphatic poly(ester-urethane) results in a low bovine serum albumin (BSA) adsorption and platelet adhesion capacity; therefore, it improves the blood compatibility of the films.

All in all, it has been shown that the hydrophilicity and protein-rejection ability of all PEG-modified coatings depend on the amount or length of the PEG derivative in the structure [18,37,38]. It is worth emphasizing that in the case of crosslinked PU networks with PEG-based dangling chains, besides the high level of water swelling problem, there is a maximum limit for the number of dangling chains can be introduced into the reaction, since the (mono-functional) dangling chains reduce the network total functionality, loosen the network, and lower the coating's mechanical integrity. Therefore, it is strongly suggested to force the majority of PEG dangling chains to migrate towards the interfacial region of the network to benefit from its outstanding interfacial properties while the bulk of the polymer remains intact [7,15,39].

In the current work, we aimed to study the incorporation of separate hydrophilic (mPEG) and hydrophobic (oDEC) dangling chains in a PU network in order to obtain the highest possible PEG concentration at the polymer/water interface. Note that, unlike most previous researches, in this study, we used a mixture of individual hydrophilic and hydrophobic dangling chains instead of employing amphiphilic block copolymers. We observed that by the addition of a small amount of the oDEC, not only the interfacial concentration of mPEG was considerably enhanced, proved by WCA and XPS, but the water uptake remained at the same level. Moreover, dynamic WCA and AFM analysis, on samples under wet and dry preconditions, proved a responsive behavior of the coatings to the environmental polarity. We also checked the coatings protein resistance ability through the BSA and lysozyme protein adsorption tests. The target structure showed a plunge in protein adsorption as a result of a limited amount of hydrophobic dangling chain insertion.