Pearl-necklace assembly of human serum albumin with the poly(acrylic acid) polyelectrolyte investigated using small angle X-ray scattering (SAXS).

In this comprehensive study, the interaction of human serum albumin (HSA) with poly(acrylic acid) (PAA) was explored using small angle X-ray scattering (SAXS) combined with chromatography. The results revealed the formation of a complex between HSA macromolecules and PAA chains but solely under some specific conditions of the ionic strength and pH of the medium. In fact, this binding was found to take place only at pH close to 5 and at low ionic strength (0.15 M). Otherwise, for a higher pH and a salt concentration of 0.75 M the HSA-PAA complex tends to dissociate completely showing the reversibility of the complexation. The assessment of the influence of the HSA/PAA molar ratio on the radius of gyration of the complex suggests that 4 HSA molecules could bind to each 100 kDa PAA chain. In addition, the Porod volume evaluation for the same range of the HSA/PAA ratio confirms this assumption. Finally, an all-atom SAXS modelling study using the BUNCH program was conducted to find a compatible model that fits the HSA-PAA complex scattering data. This model allows us to portray the HSA/PAA complex as a pearl-necklace assembly with 4 HSA molecules on the 100 kDa PAA chain.

Designs of Zwitterionic Interfaces and Membranes.

Zwitterionic materials are the latest generation of materials for nonfouling interfaces and membranes. They outperform poly(ethylene glycol) derivatives because they form tighter bonds with water molecules and can trap more water molecules. This feature article summarizes our laboratory's fundamental developments related to the functionalization of interfaces and membranes using zwitterionic materials. Our molecular designs of zwitterionic polymers and copolymers, sulfobetaine-based, carboxybetaine-based, or phosphobetaine-based, are first reviewed. Then, the strategies used to functionalize surfaces/membranes by coating, grafting onto, grafting from, or in situ modification are examined and discussed, and the third part of this article shifts the focus to key applications of zwitterionic materials. Finally, some potential future directions for molecular designs, functionalization processes, and applications are presented.

Self-Cleaning Interfaces of Polydimethylsiloxane Grafted with pH-Responsive Zwitterionic Copolymers.

Self-cleaning surfaces allow the reversible attachment and detachment of microorganisms which show great promise in regards to their reusability as smart biomaterials. However, a widely used biomaterial such as polydimethylsiloxane (PDMS) suffers from high biofouling activity and hydrophobic recovery that results in decreased efficiency and stability. A current challenge is to modify and fabricate self-cleaning PDMS surfaces by incorporating antifouling and pH-sensitive properties. To address this, we synthesized a zwitterionic and pH-sensitive random poly(glycidyl methacrylate- co-sulfobetaine methacrylate- co-2-(dimethylamino)ethyl methacrylate) polymer, poly(GMA- co-SBMA- co-DMAEMA). In this work, chemical modification of PDMS was done by grafting onto poly(GMA- co-SBMA- co-DMAEMA) after surface activation via UV and ozone for 90 min to ensure the formation of covalent bonds necessary for stable grafting. The PDMS grafted with G20-S40-D40 exhibit antifouling and pH-sensitive properties by mitigating fibrinogen adsorption, blood cell adhesion, and releasing 98% adhered E. coli bacteria after immersion at basic pH. The grafting of poly(GMA- co-SBMA- co-DMAEMA) presented in this work shows attractive potential for biomedical and industrial applications as a simple, smart, and effective method for the modification of PDMS interfaces.

Toward Antibiofouling PVDF Membranes.

Membranes for biologically and biomedically related applications must be bioinert, that is, resist biofouling by proteins, human cells, bacteria, algae, etc. Hydrophobic materials such as polysulfone, polypropylene, or poly(vinylidene fluoride) (PVDF) are often chosen as matrix materials but their hydrophobicity make them prone to biofouling, which in turn limits their application in biological/biomedical fields. Here, we designed PVDF-based membranes by precipitation from the vapor phase and zwitterionized them in situ to reduce their propensity to biofouling. To achieve this goal, we used a copolymer containing phosphorylcholine groups. An in-depth physicochemical characterization revealed not only the controlled presence of the copolymer in the membrane but also that bicontinuous membranes could be formed. Membrane hydrophilicity was greatly improved, resulting in the mitigation of a variety of biofoulants: the attachment of Stenotrophomonas maltophilia, Streptococcus mutans, and platelets was reduced by 99.9, 99.9, and 98.9%, respectively. Besides, despite incubation in a plasma platelet-poor medium, rich in plasma proteins, a flux recovery ratio of 75% could be measured while it was only 40% with a hydrophilic commercial membrane of similar structure and physical properties. Similarly, the zwitterionic membrane severely mitigated biofouling by microalgae during their harvesting. All in all, the material/process combination presented in this work leads to antibiofouling porous membranes with a large span of potential biomedically and biologically related applications.

Bioinert Control of Zwitterionic Poly(ethylene terephtalate) Fibrous Membranes.

Poly(ethylene terephtalate) (PET)-based materials face general biofouling issues that we addressed by grafting a copolymer of glycidyl methacrylate and sulfobetaine methacrylate, poly(GMA- r-SBMA). The grafting procedure involved a dip-coating step followed by UV-exposure and led to successful grafting of the copolymer as evidenced by X-ray photoelectron spectroscopy and zeta potential measurements. It did not modify the pore size nor the porosity of the PET membranes. In addition, their surface hydrophilicity was considerably improved, with a water contact angle falling to 30° in less than 20 s and 0° in less than 1 min. The effect of copolymer concentration in the coating bath (dip-coating procedure) and UV exposure time (UV step) were scrutinized during biofouling studies involving several bacteria such as Escherichia coli and Stenotrophomonas maltophilia, but also whole blood and HT1080 fibroblasts cells. The results indicate that if all conditions led to improved biofouling mitigation, due to the efficiency of the zwitterionic copolymer and grafting procedure, a higher concentration (15 mg/mL) and longer UV exposure time (at least 10 min) enhanced the grafting density which reflected on the biofouling results and permitted a better general biofouling control regardless of the nature of the biofoulant (bacteria, blood cells, fibroblasts).

Zwitterionic Polyhydroxybutyrate Electrospun Fibrous Membranes with a Compromise of Bioinert Control and Tissue-Cell Growth.

We present a method for surface modification by thermal-evaporation self-assembling of poly(3-hydroxybutyrate) (PHB) fibrous membranes with a copolymer of hydrophobic octadecyl acrylate repeat units and hydrophilic zwitterionic 4-vinylpyridine blocks, zP(4VP-r-ODA), in view of controlling biofoulant-fiber interactions. PHB is of interest as a material for bioscaffolding, but its disadvantage is its hydrophobicity, which leads to unwanted interactions with proteins, blood cells, or bacteria. Surface modification of electrospun PHB fibers addresses this issue because the hydrophilicity of the membranes is improved, leading to a significant reduction in bovine serum albumin (92%), lysozyme (73%), and fibrinogen (50%) adsorption. From a coating density of 0.78 mg/cm2, no bacteria interacted with the fibers, and from 1.13 mg/cm2, excellent hemocompatibility of membranes was measured from thrombocytes, erythrocytes, leukocytes, and whole blood attachment tests. Additionally, HT-1080 fibroblasts were observed to develop in contact with the fibers after 3-7 days of incubation (cell density up to 329 ± 16 cells/mm2), suggesting that zP(4VP-r-ODA) provides an adequate humid environment for their growth. Providing an effective control of the surface chemistry and of the coating density, the association of PHB and zP(4VP-r-ODA) can promote the growth of fibroblasts, still maintaining resistance to unwanted biofoulants, and appears to be a promising composite material for tissue engineering.

Epoxylated Zwitterionic Triblock Copolymers Grafted onto Metallic Surfaces for General Biofouling Mitigation.

Titanium and stainless steel materials are widely used in numerous devices or in custom parts for their excellent mechanical properties. However, their lack of biocompatibility seriously limits their usage in the biomedical field. This study focuses on the grafting of triblock copolymers on titanium and stainless steel metal susbtrates for improving their general biofouling resistance. The series of copolymers that we designed is composed of two blocks of zwitterionic sulfobetaine (SBMA) monomers and one block of glycidyl methacrylate (GMA). The number of repeat units forming each block, n, was finely tuned and controlled to 25, 50, 75, or 100, permitting regulation of the grafting thickness, the morphology, and the dependent properties such as the surface hydrophilicity and biofouling resistance. It was shown that the copolymer possessing n = 50 repeat units in each block, corresponding to a molecular weight of about 15.2 kDa, led to the best nonfouling properties, assessed using plasma proteins, blood cells, fibroblasts cells, and various bacteria. This was explained by an optimized grafting degree and chain organization of the copolymer. Lower value (n = 25) and higher values (n = 75, 100) led to low surface coverage and the formation of aggregates, respectively. The best copolymer was grafted onto scalpels (steel) and dental roots (titanium), and antifouling properties demonstrated using Escherichia coli and HT1080 cells. Results of this work show that this unique triblock copolymer holds promise as a potential material for surface modification of biomedical metallic devices, provided a fine-tuning of the blocks organization and length.

A Zwitterionic-Shielded Carrier with pH-Modulated Reversible Self-Assembly for Gene Transfection.

Cationic vectors are ideal candidates for gene delivery thanks to their capability to carry large gene inserts and their scalable production. However, their cationic density gives rise to high cytotoxicity. We present the proper designed core-shell polyplexes made of either poly(ethylene imine) (PEI) or poly(2-dimethylamino ethyl methacrylate) (PDMAEMA) as the core and zwitterionic poly(acrylic acid)-block-poly(sulfobetaine methacrylate) (PAA-b-PSBMA) diblock copolymer as the shell. Gel retardation and ethidium bromide displacement assays were used to determine the PEI/DNA or PDMAEMA/DNA complexation. At neutral pH, the copolymer serves as a protective shell of the complex. As PSBMA is a nonfouling block, the shell reduced the cytotoxicity and enhanced the hemocompatibility (lower hemolysis activity, longer plasma clotting time) of the gene carriers. PAA segments in the copolymer impart pH sensitivity by allowing deshielding of the core in acidic solution. Therefore, the transfection efficiency of polyplexes at pH 6.5 was better than at pH 7.0, from ß-galactosidase assay, and for all PAA-b-PSBMA tested. These results were supported by more favorable physicochemical properties in acidic solution (zeta potential, particle size, and interactions between the polymer and DNA). Thus, the results of this study offer a potential route to the development of efficient and nontoxic pH-sensitive gene carriers.

Zwitterionic Modifications for Enhancing the Antifouling Properties of Poly(vinylidene fluoride) Membranes.

The development of effective antibiofouling membranes is critical for many scientific interests and industrial applications. However, the existing available membranes often suffer from the lack of efficient, stable, and scalable antifouling modification strategy. Herein, we designed, synthesized, and characterized alternate copolymers of p(MAO-DMEA) (obtained by reaction between poly(maleic anhydride-alt-1-octadecene) and N,N-dimethylenediamine) and p(MAO-DMPA) (obtained by reaction between poly(maleic anhydride-alt-1-octadecene) and 3-(dimethylamino)-1-propylamine) of different carbon space length (CSL) using a ring-opening zwitterionization. We coated these copolymers on poly(vinylidene fluoride) (PVDF) membranes using a self-assembled anchoring method. Two important design parameters-the CSL of polymers and the coating density of polymers on membrane-were extensively examined for their effects on the antifouling performance of the modified membranes using a series of protein, cell, and bacterial assays. Both zwitterionic-modified membranes with different coating densities showed improved membrane hydrophilicity, increased resistance to protein, bacteria, blood cells, and platelet adsorption. However, while p(MAO-DMEA) with two CSLs and p(MAO-DMPA) with three CSLs only differ by one single carbon between the amino and ammonium groups, such subtle structural difference between the two polymers led to the fact that the membranes self-assembled with MAO-DMEA outperformed those modified with MAO-DMPA in all aspects of surface hydration, protein and bacteria resistance, and blood biocompatibility. This work provides an important structural-based design principle: a subtle change in the CSL of polymers affects the surface and antifouling properties of the membranes. It can help to achieve the design of more effective antifouling membranes for blood contacting applications.

Stimuli-responsive and hemocompatible pseudozwitterionic interfaces.

We report a novel biomacromolecular formula for the design of hemocompatible gel interfaces of N-isopropylacrylamide (NIPAAm) and mixed-charge pairs of [2-(methacryloyloxy)ethyl]trimethylammonium (TMA) and 3-sulfopropyl methacrylate (SA) with overall electrical neutrality. The study stresses on how well-defined compositions of nonionic NIPAAm and pseudozwitterionic TMA/SA in the poly(NIPAAm-co-TMA/SA) hydrogels along with environmental conditions (temperature, ionic strength, and solution pH) affect swelling and adhesion of biofoulants on their surfaces. When challenged with plasma proteins, bacteria, recalcified platelets, or whole blood, stimuli-responsive hydrogels better resisted their adhesion as the content of mixed charges in the copolymer increased, to reach nonbiofouling for the gels made of 100% TMA/SA. The low hemolytic activity (0.5%) associated with a long plasma clotting time (10 min) suggests excellent hemocompatibility excellent hemocompatibility. Finally, hydrogels containing both NIPAAm and TMA/SA tend to exhibit preferential adhesion of leukocytes.

Surface hydrophilicity and morphology control of anti-biofouling polysulfone membranes via vapor-induced phase separation processing.

We report in this study the formation of low-biofouling polysulfone (PSf) membranes by vapor-induced phase separation. Membranes were prepared by blending an amphiphilic additive, Pluronic F108, Pluronic F127 or 3-(N,N-Dimethylmyristylammonio)propane-sulfonate (DMMSAPS) with PSf, before inducing phase separation of the solution. The additive affected both membrane morphology and surface chemical composition. F127 and DMMSAPS tended to increase the porosity of membranes, while the final structure of membranes prepared with F108 were close to that of virgin PSf membrane. The additive molecular weight as well as micelle formation is believed to be responsible for these different porous structures. Whatever the additive, hydrophilicity of membranes was enhanced. Protein adsorption tests performed with PEGylated PSf membranes revealed that both F108 and F127 led to a decreasing of biofouling, but better performances were obtained using F127 for which stronger interactions with membrane matrices were achieved.

Recent Advances on the Fabrication of Antifouling Phase-Inversion Membranes by Physical Blending Modification Method.

Membrane technology is an essential tool for water treatment and biomedical applications. Despite their extensive use in these fields, polymeric-based membranes still face several challenges, including instability, low mechanical strength, and propensity to fouling. The latter point has attracted the attention of numerous teams worldwide developing antifouling materials for membranes and interfaces. A convenient method to prepare antifouling membranes is via physical blending (or simply blending), which is a one-step method that consists of mixing the main matrix polymer and the antifouling material prior to casting and film formation by a phase inversion process. This review focuses on the recent development (past 10 years) of antifouling membranes via this method and uses different phase-inversion processes including liquid-induced phase separation, vapor induced phase separation, and thermally induced phase separation. Antifouling materials used in these recent studies including polymers, metals, ceramics, and carbon-based and porous nanomaterials are also surveyed. Furthermore, the assessment of antifouling properties and performances are extensively summarized. Finally, we conclude this review with a list of technical and scientific challenges that still need to be overcome to improve the functional properties and widen the range of applications of antifouling membranes prepared by blending modification.

Leveraging the Dielectric Barrier Discharge Plasma Process to Create Regenerative Biocidal ePTFE Membranes.

The utilization of dielectric barrier discharge (DBD) plasma treatment for modifying substrate surfaces constitutes an easy and simple approach with a potential for diverse applications. This technique was used to modify the surface of a commercial porous expanded poly(tetrafluoroethylene) (ePTFE) film with either dimethylaminoethyl methacrylate (DMAEMA) or (trimethylamino)ethyl methacrylate chloride (TMAEMA) monomers, aiming to obtain antibacterial ePTFE. Physicochemical analyses of the membranes revealed that DBD successfully enhanced the surface energy and surface charge of the membranes while maintaining high porosity (>75%) and large pore size (>1.0 µm). Evaluation of the bacteria killing-releasing (K-R) function revealed that both DMAEMA and TMAEMA endowed ePTFE with the ability to kill Escherichia coli bacteria. However, only TMAEMA-grafted ePTFE allowed for the release of dead bacteria from the surface upon washing with sodium hexametaphosphate (SHMP) saline solution, owing to its cationic charge derived from the quaternary amine. Washing with SHMP disturbed the electrostatic force between the polymer brushes and dead bacteria, which caused the release of the dead bacteria. Lastly, dead-end bacteria filtration showed that the TMAEMA-grafted ePTFE was able to kill 99.78% of the bacteria, while approximately 61.55% of bacteria were killed upon contact. The present findings support the feasibility of using DBD plasma treatment for designing surfaces that target bacteria and aid in the containment of disease-causing pathogens.

A Green Stable Antifouling PEGylated PVDF Membrane Prepared by Vapor-Induced Phase Separation.

While green solvents are being implemented in the fabrication of polyvinylidene fluoride (PVDF) membranes, most are not compatible with the vapor-induced phase separation (VIPS) process for which relatively low dissolution temperatures are required. Additionally, preparing antifouling green membranes in one step by blending the polymer with an antifouling material before inducing phase separation remains extremely challenging due to the solubility issues. Here, the green solvent triethyl phosphate (TEP) was used to solubilize both PVDF and a copolymer (synthesized from styrene monomer and poly(ethylene glycol) methyl ether methacrylate). VIPS was then used, yielding symmetric bi-continuous microfiltration membranes. For a 2 wt% copolymer content in the casting solution, the corresponding membrane P2 showed a homogeneous and dense surface distribution of the copolymer, resulting in a high hydration capacity (>900 mg/cm3) and effective resistance to biofouling during the adsorption tests using bovine serum albumin, Escherichia coli or whole blood, with a measured fouling reduction of 80%, 89% and 90%, respectively. Cyclic filtration tests using bacteria highlighted the competitive antifouling properties of the membranes with a flux recovery ratio after two water/bacterial solution cycles higher than 70%, a reversible flux decline ratio of about 62% and an irreversible flux decline ratio of 28%. Finally, these green antifouling membranes were shown to be stable despite several weeks of immersion in water.

A Biofouling Resistant Zwitterionic Polysulfone Membrane Prepared by a Dual-Bath Procedure.

This study introduces a zwitterionic material to modify polysulfone (PSf) membranes formed by a dual bath procedure, in view of reducing their fouling propensity. The zwitterionic copolymer, derived from a random polymer of styrene and 4-vinylpyrridine and referred to as zP(S-r-4VP), was incorporated to the PSf solution without any supplementary pore-forming additive to study the effect of the sole copolymer on membrane-structuring, chemical, and arising properties. XPS and mapping FT-IR provided evidence of the modification. Macrovoids appeared and then disappeared as the copolymer content increased in the range 1-4 wt%. The copolymer has hydrophilic units and its addition increases the casting solution viscosity. Both effects play an opposite role on transfers, and so on the growth of macrovoids. Biofouling tests demonstrated the efficiency of the copolymer to mitigate biofouling with a reduction in bacterial and blood cell attachment by more than 85%. Filtration tests revealed that the permeability increased by a twofold factor, the flux recovery ratio was augmented from 40% to 63% after water/BSA cycles, and irreversible fouling was reduced by 1/3. Although improvements are needed, these zwitterionic PSf membranes could be used in biomedical applications where resistance to biofouling by cells is a requirement.

Dopamine-Induced Surface Zwitterionization of Expanded Poly(tetrafluoroethylene) for Constructing Thermostable Bioinert Materials.

Although energy-demanding, the surface modification of polytetrafluoroethylene (PTFE) for biomedical applications is mandatory to mitigate irreversible biofouling that occurs whenever PTFE comes into contact with biological fluids. Here, we propose to take advantage of the adhesive properties of dopamine (DA) and of the antifouling ability of various zwitterionic monomers (sulfobetaine methacrylate (SBMA), sulfobetaine methacrylamide (SBAA), sulfobetaine acrylamide (SBAA'), and 4-vinylpyridine propylsulfobetaine (4VPPS)) and form antifouling coatings by copolymerization on the surface of expanded PTFE membranes. This simple, low-energy, and one-step coating procedure arises in significant biofouling mitigation. All zwitterionic coatings led to important reduction of biofouling by red blood cell conentrate (88-94%), platelet conentrate (70-90%), whole blood (40-66%), or bacteria (83-96%). Also, it is shown that the interactions of polydopamine with ePTFE are stable even at high temperatures. However, the zwitterionic monomers are differently affected. While the performance of SBMA coatings decreased (as SBMA is prone to hydrolysis), those of SBAA, SBAA', and 4VPPS coatings were generally maintained. All in all, this study illustrates that efficient and stable antifouling zwitterionic coatings can be generated onto PTFE membranes for biomedical applications, without the use of conventional high-energy-demanding surface modification processes.

Surface PEGylation via Ultrasonic Spray Deposition for the Biofouling Mitigation of Biomedical Interfaces.

Air plasma and spray technology are common methods for surface modification. In this study, air plasma is used to generate hydroxyl groups on various material surfaces. Then random copolymers of styrene and ethylene glycol methacrylate (PS-r-PEGMA) are spray-coated to achieve coating densities ranging between 0.1 and 0.6 mg/cm2. PS50-r-PEGMA50 led to the best overall antifouling properties, while a coating density of 0.3 mg/cm2 was enough to significantly reduce biofouling. This surface modification technique enabled efficient modification of a wide range of materials and biofouling reduction by at least 75% on polymeric surfaces (polystyrene, polyvinylidene fluoride, poly(tetrafluoroethylene), polydimethylsiloxane), metallic surfaces (steel, titanium alloy), or ceramic surface (glass). Applied to the modification of well plate used for blood-typing, this antifouling modification permitted to greatly increase the signal sensitivity (×4).

Thermally Stable Bioinert Zwitterionic Sulfobetaine Interfaces Tolerated in the Medical Sterilization Process.

This work introduces a thermally stable zwitterionic structure able to withstand steam sterilization as a general antifouling medical device interface. The sulfobetaine methacrylate (SBMA) monomer and its polymer form are among the most widely used zwitterionic materials. They are easy to synthesize and have good antifouling properties. However, they partially lose their properties after steam sterilization, a common procedure used to sterilize biomedical interfaces. In this study, ultrahigh-performance liquid chromatography/mass spectrometry (UHPLC-MS) was used to analyze and discuss the molecular structure of SBMA before and after a steam sterilization procedure, and a strategy to address the thermal stability issue proposed, using sulfobetaine methacrylamide (SBAA) instead of SBMA. Interestingly, it was found that the chemical structure of SBAA material can withstand the medical sterilization process at 121 °C while maintaining good antifouling properties, tested with proteins (fibrinogen), bacteria (Escherichia coli), and whole blood. On the other hand, SBMA gels failed at maintaining their excellent antifouling properties after sterilization. This study suggests that the SBAA structure can be used to replace SBMA in the bioinert interface of sterilizable medical devices, such as rayon fiber membranes used for disease control.

Zwitterionized Nanofibrous Poly(vinylidene fluoride) Membranes for Improving the Healing of Diabetic Wounds.

This work presents nanofibrous membranes made of poly(vinylidene fluoride) (PVDF) and poly(2-methacryloyloxyethyl phosphorylcholine-co-methacryloyloxyethyl butylurethane) (PMBU) for promoting the healing of acute and chronic wounds. Membranes were prepared by an electrospinning process, which led to matrixes with a pore size mimicking the extracellular matrix. PMBU greatly improves the hydration of membranes, resulting in very low biofouling by protein or bacteria and enhanced blood compatibility while the cell viability remains close to 100%. This set of properties exhibited by the suitable combination of physical structure and material composition led to applying the zwitterionic nanofibrous membranes as wound-dressing materials for acute and chronic wounds. The results demonstrated that the zwitterionic membrane could compete with commercial dressings in terms of wound-healing kinetics and could outperform them with regard to the quality of new tissue. Histological analyses suggested that inflammation was reduced while proliferative and maturation phases were accelerated, leading to homogeneous re-epithelialization. This study unveils another potential biomedical application of antifouling zwitterionic membranes.

Temperature-triggered attachment and detachment of general human bio-foulants on zwitterionic polydimethylsiloxane.

Biofouling has long been a problem for biomaterials, so being able to control the fouling on the surface of a biomaterial would be ideal. In this study a copolymer system was designed comprising three moieties: an epoxy containing group, glycidyl methacrylate (GMA); a thermoresponsive segment, N-isopropylacrylamide (NIPAAm); and an antifouling zwitterionic unit, sulfobetaine methacrylate (SBMA). The copolymers (pGSN), synthesized via free radical polymerization with these 3 moieties, were then grafted onto polydimethylsiloxane (PDMS). The presence of a critical temperature for both the copolymers and the coated PDMS was evidenced by particle size and contact angle measurements. The coated PDMS exhibited controllable temperature-dependent antifouling behaviors and stimuli-responsive phase characteristics in the presence of salts. The interactions of the coated PDMS with biomolecules were tested via attachment of fibrinogen protein, platelets, human whole blood, and tumor cells (HT1080). The attachment and detachment of these biomolecules were studied at different temperatures. Exposed hydrophobic domains of thermoresponsive NIPAAm-rich pGSN containing NIPAAm at 56 mol% generally allows molecular and cellular attachment on the PDMS surface at 37 °C. On the other hand, the coated PDMS with a relatively high content of SBMA (>41 mol%) in the copolymer started to exhibit fouling resistance and lower the thermoresponsive properties. Interestingly, the incorporation of zwitterionic SBMA units into the copolymers was found to accelerate the hydration of the PDMS surfaces and resulted in biomolecular and cellular detachment at 25 °C, which is comparable to the detachment at 4 °C. This modified surface behavior is found to be consistent through all biofouling tests.