High-density zwitterionic polymer brushes exhibit robust lubrication properties and high antithrombotic efficacy in blood-contacting medical devices.

High-performance catheters are essential for interventional surgeries, requiring reliable anti-adhesive and lubricated surfaces. This article develops a strategy for constructing high-density sulfobetaine zwitterionic polymer brushes on the surface of catheters, utilizing dopamine and sodium alginate as the primary intermediate layers, where dopamine provides mussel-protein-like adhesion to anchor the polymer brushes to the catheter surface. Hydroxyl-rich sodium alginate increases the number of grafting sites and improves the grafting mass by more than 4 times. The developed high-density zwitterionic polymer brushes achieve long-lasting and effective lubricity (µ<0.0078) and are implanted in rabbits for four hours without bio-adhesion and thrombosis in the absence of anticoagulants such as heparin. Experiments and molecular dynamics simulations demonstrate that graft mass plays a decisive role in the lubricity and anti-adhesion of polymer brushes, and it is proposed to predict the anti-adhesion of polymer brushes by their lubricity to avoid costly and time-consuming bioassays during the development of amphoteric polymer brushes. A quantitative influence of hydration in the anti-adhesion properties of amphiphilic polymer brushes is also revealed. Thus, this study provides a new approach to safe, long-lasting lubrication and anticoagulant surface modification for medical devices in contact with blood. STATEMENT OF SIGNIFICANCE: High friction and bioadhesion on medical device surfaces can pose a significant risk to patients. In response, we have developed a safer, simpler, and more application-specific surface modification strategy that addresses both the lubrication and anti-bioadhesion needs of medical device surfaces. We used dopamine and sodium alginate as intermediate layers to drastically increase the grafting density of the zwitterionic brushes and enabled the modified surfaces to have an extremely low coefficient of friction (µ = 0.0078) and to remain non-bioadhesive for 4 hours in vivo. Furthermore, we used molecular dynamics simulations to gain insight into the mechanisms behind the superior anti-adhesion properties of the high-density polymer brushes. Our work contributes to the development and application of surface-modified coatings.

Biomaterials coated with zwitterionic polymer brush demonstrated significant resistance to bacterial adhesion and biofilm formation in comparison to brush coatings incorporated with antibiotics.

A critical problem with the use of biomaterial implants is associated with bacterial adhesion on the surface of implants and in turn the biofilm formation. Among different strategies that have been reported to resolve this dilemma, surface design combined with both antiadhesive and antimicrobial properties has proven to be highly effective. Physiochemical properties of polymer brush coatings possess non-adhesive capability against bacterial adhesion and create a niche for further functionalization. The current study aims to evaluate the effect of antibiotics incorporated into the polymer brush on bacterial adhesion and biofilm formation. Brushes made of zwitterionic polymers were synthesized, functionalized with vancomycin via both physical and chemical conjugation, and grafted onto the silicon rubber surfaces. Antibacterial and antiadhesive measurements of designed coated biomaterials were mediated through the use of a parallel plate flow chamber against biofilm growth developed by Staphylococcus aureus and Escherichia coli over a period of 24 h. The analysis of biofilm growth on designed coated biomaterials showed that the pristine coated zwitterionic brushes are significantly resistant to bacterial adhesion and biofilm formation but not in the polymer brush coating incorporated with antibiotics.

Fouling Resistance and Release Properties of Poly(sulfobetaine) Brushes with Varying Alkyl Chain Spacer Lengths and Molecular Weights.

We examined the effects of alkyl carbon spacer length (CSL) and molecular weight on fouling resistance and release properties of zwitterionic poly(sulfobetaine methacrylate) brushes. Using surface-initiated atom transfer radical polymerization, we synthesized two series of brushes with CSL = 3 and 4 and molecular weight from 19 to 1500 kg ·mol-1, corresponding to dry brush thickness from around 6 to 180 nm. The brush with CSL = 3 was nearly completely wet with water (independent of molecular weight), whereas the brush with CSL = 4 exhibited a strong increase in water contact angle with molecular weight. Though the two-brush series had distinct wetting properties, both series of brushes exhibited similarly great resistance against fouling by Staphylococcus epidermidis bacteria and Aspergillus niger fungi spores when submerged in water, indicating that neither molecular weight nor CSL strongly affected the antifouling behavior. We also compared the efficacy of brushes against fouling by fungi and silicon oil in air. Brushes grafted to filter paper were strongly fouled by fungi and silicon oil in air. Grafting the polymers to the filter paper, however, greatly enhanced removal of the foulant upon rinsing. The removal of fungi and silicon oil when rinsed with a salt solution was enhanced by 219 and 175%, respectively, as compared to a blank filter paper control. Thus, our results indicate that these zwitterionic brushes can promote foulant removal for dry applications in addition to their well-known fouling resistance in submerged conditions.

An On-Skin Electrode with Anti-Epidermal-Surface-Lipid Function Based on a Zwitterionic Polymer Brush.

On-skin flexible devices provide a noninvasive approach for continuous and real-time acquisition of biological signals from the skin, which is essential for future chronic disease diagnosis and smart health monitoring. Great progress has been achieved in flexible devices to resolve the mechanical mismatching between conventional rigid devices and human skin. However, common materials used for flexible devices including silicon-based elastomers and various metals exhibit no resistance to epidermal surface lipids (skin oil and grease), which restricts the long-term and household usability. Herein, an on-skin electrode with anti-epidermal-surface-lipid function is reported, which is based on the grafting of a zwitterionic poly(2-methacryl-oyloxyethyl, methacryloyl-oxyethyl, or meth-acryloyloxyethyl phosphorylcholine) (PMPC) brush on top of gold-coated poly(dimethylsiloxane) (Au/PDMS). Such an electrode allows the skin-lipids-fouled surface to be cleaned by simple water rinsing owing to the superhydrophilic zwitterionic groups. As a proof-of-concept, the PMPC-Au/PDMS electrodes are employed for both electrocardiography (ECG) and electromyography (EMG) recording. The electrodes are able to maintain stable skin-electrode impedance and good signal-to noise ratio (SNR) by water rinsing alone. This work provides a material-based solution to improve the long-term reusability of on-skin electronics and offers a unique prospective on developing next generation wearable healthcare devices.

Surface-grafted zwitterionic polymers improve the efficacy of a single antibiotic injection in suppressing S. aureus periprosthetic infections.

Implant-associated bacterial infections are difficult to treat due to the tendency of biofilm formation on implant surfaces, which protects embedded pathogens from host defense and impedes antibiotic penetration, rendering systemic antibiotic injections ineffective. Here, we test the hypothesis that implant coatings that reduce bacterial colonization would make planktonic bacteria within the periprosthetic environment more susceptible to conventional systemic antibiotic treatment. We covalently grafted zwitterionic polymer brushes poly(sulfobetaine methacryate) from Ti6Al4V surface to increase the substrate surface hydrophilicity and reduce staphylococcus aureus (S. aureus) adhesion. Using a mouse femoral intramedullary (IM) canal infection model, we showed that the anti-fouling coating applied to Ti6Al4V IM implants, when combined with a single vancomycin systemic injection, significantly suppressed both bacterial colonization on implant surfaces and the periprosthetic infections, outperforming either treatment alone. This work supports the hypothesis that grafting anti-fouling polymers to implant surfaces improves the efficacy of systemic antibiotic injections to combat periprosthetic infections.

Gradation of proteins and cells attached to the surface of bio-inert zwitterionic polymer brush.

A self-assembled monolayer (SAM) of a 2-bromoisobutyryl end group-carrying initiator for atom transfer radical polymerization (ATRP) was constructed on the surface of silicon wafer or glass substrates via a silane-coupling reaction. When the initiator SAM was irradiated with UV light at 254nm, the surface density of bromine atoms was reduced by the scission of CBr bonds as observed by XPS. With the surface-initiated ATRP of the zwitterionic vinyl monomer, carboxymethyl betaine (CMB), the surface density of PCMB brushes could be easily varied by changing the irradiation period of UV light prior to the polymerization. Furthermore, by using a UV-cut shutter sliding above the initiator SAM-modified substrate at a constant speed, the degree of bromine atom removal could be linearly varied along the direction of movement of the shutter. Consequently, the amount of both proteins adsorbed and cells adhered to the PCMB brush-covered substrate could easily be controlled by the gradation of the surface density of PCMB brushes, which suppressed protein adsorption and cell adhesion. Such a technique is very simple and useful for the regulation of the surface density of adsorbed proteins and adhered cells on an originally bio-inert surface.

Molecular Design of Antifouling Polymer Brushes Using Sequence-Specific Peptoids.

Material systems that can be used to flexibly and precisely define the chemical nature and molecular arrangement of a surface would be invaluable for the control of complex biointerfacial interactions. For example, progress in antifouling polymer biointerfaces that prevent non-specific protein adsorption and cell attachment, which can significantly improve the performance of an array of biomedical and industrial applications, is hampered by a lack of chemical models to identify the molecular features conferring their properties. Poly(N-substituted glycine) "peptoids" are peptidomimetic polymers that can be conveniently synthesized with specific monomer sequences and chain lengths, and are presented as a versatile platform for investigating the molecular design of antifouling polymer brushes. Zwitterionic antifouling polymer brushes have captured significant recent attention, and a targeted library of zwitterionic peptoid brushes with a different charge densities, hydration, separations between charged groups, chain lengths, and grafted chain densities, is quantitatively evaluated for their antifouling properties through a range of protein adsorption and cell attachment assays. Specific zwitterionic brush designs were found to give rise to distinct but subtle differences in properties. The results also point to the dominant roles of the grafted chain density and chain length in determining the performance of antifouling polymer brushes.

Patterning of photocleavable zwitterionic polymer brush fabricated on silicon wafer.

Brushes of a polymer, namely poly(carboxymethylbetaine) (PCMB), were fabricated on silicon wafers by reversible addition-fragmentation chain-transfer (RAFT) polymerization using a surface-confined RAFT agent having an aromatic group at its bottom. The polymer brush showed effective suppression of the non-specific adsorption of bovine serum albumin (BSA) and adhesion of fibroblasts (3T3 cells). In contrast, BSA and 3T3 cells significantly adsorbed on and adhered to positively or negatively charged polymer brushes fabricated by the same procedure. Upon UV irradiation at 193 nm, the thickness of the PCMB brush with an aromatic group at its bottom decreased significantly whereas PCMB prepared using a surface-confined RAFT agent without an aromatic group needed a much higher irradiation dose to afford a comparable decrease in thickness. These results indicate a preferential cleavage of the PCMB brush due to photodecomposition of the phenyl group at the bottom. BSA and 3T3 cells non-specifically adsorbed on and adhered to the UV irradiation-induced hollow spaces, respectively. Furthermore, a designed pattern with a resolution of 5 µm was successfully made on the PCMB brush above the silicon wafer by simple UV irradiation. These results suggest that the surface-confined aromatic RAFT agent will be quite useful for simple photolithography in biomedical fields.