An ideal nonbiofouling surface for biomedical applications requires both high-efficient antifouling characteristics in relation to biological components and long-term material stability from biological systems. In this study we demonstrate the performance and stability of an antifouling surface with grafted zwitterionic sulfobetaine methacrylate (SBMA). The SBMA was grafted from a bromide-covered gold surface via surface-initiated atom transfer radical polymerization to form well-packed polymer brushes. Plasma protein adsorption on poly(sulfobetaine methacrylate) (polySBMA) grafted surfaces was measured with a surface plasmon resonance sensor. It is revealed that an excellent stable nonbiofouling surface with grafted polySBMA can be performed with a cycling test of the adsorption of three model proteins in a wide range of various salt types, buffer compositions, solution pH levels, and temperatures. This work also demonstrates the adsorption of plasma proteins and the adhesion of platelets from human blood plasma on the polySBMA grafted surface. It was found that the polySBMA grafted surface effectively reduces the plasma protein adsorption from platelet-poor plasma solution to a level superior to that of adsorption on a surface terminated with tetra(ethylene glycol). The adhesion and activation of platelets from platelet-rich plasma solution were not observed on the polySBMA grafted surface. This work further concludes that a surface with good hemocompatibility can be achieved by the well-packed surface-grafted polySBMA brushes.

In this work, the hemocompatibility of a sulfobetaine-like copolymer brush resulting from a mixed-charge copolymerization of the positively charged 11-mercapto-N,N,N-trimethylammonium chloride (TMA) and negatively charged 11-mercaptoundecylsulfonic acid (SA) was studied. Mixed charge distribution in the prepared poly(TMA-co-SA) copolymer brushes was controlled by the regulation of the reaction rate of the surface-initiated atom transfer radical polymerization (ATRP). The adsorption behavior of plasma proteins on a surface grafted with poly(TMA-co-SA) was measured by a surface plasmon resonance (SPR) sensor. The effects of varying temperature, solution pH, and ionic strength on the antifouling characteristics of the mixed-charge copolymer brushes were systematically evaluated, and the protein-fouling resistance was discussed in detail, especially with respect to the effect of ionic strength on the intra- and intermolecular interactions of the poly(TMA-co-SA) with proteins. The adhesion and activation of blood cells on the poly(TMA-co-SA)-grafted surface in contact with human whole blood was also demonstrated. The results suggest that mixed-charge copolymer brushes of poly(TMA-co-SA), which, like zwitterionic homopolymer brushes, have overall charge neutrality, can be used in similar applications for protein-fouling resistance and have excellent hemocompatibility with human whole blood at physiologic temperatures.

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Thermoresponsive statistical copolymers of zwitterionic sulfobetaine methacrylate (SBMA) and nonionic N-isopropylacrylamide (NIPAAm) were prepared with an average molecular weight of about 6.0 kDa via homogeneous free radical copolymerization. The aqueous solution properties of poly(SBMA-co-NIPAAm) were measured using a UV--visible spectrophotometer. The copolymers exhibited controllable lower and upper critical solution temperatures in aqueous solution and showed stimuli-responsive phase transition in the presence of salts. Regulated zwitterionic and nonionic molar mass ratios led to poly(SBMA-co-NIPAAm) copolymers having double-critical solution temperatures, where the water-insoluble polymer microdomains are generated by the zwitterionic copolymer region of polySBMA or nonionic copolymer region of polyNIPAAm depending on temperature. A high content of the nonionic polyNIPAAm in poly(SBMA-co-NIPAAm) exhibits nonionic aggregation at high temperatures due to the desolvation of polyNIPAAm, whereas relatively low content of polyNIPAAm in poly(SBMA-co-NIPAAm) exhibits zwitterionic aggregation at low temperatures due to the desolvation of polySBMA. Plasma protein adsorption on the surface coated with poly(SBMA-co-NIPAAm) was measured with a surface plasmon resonance (SPR) sensor. The copolymers containing polySBMA above 29 mol % showed extremely low protein adsorption and high anticoagulant activity in human blood plasma. The tunable and switchable thermoresponsive phase behavior of poly(SBMA-co-NIPAAm), as well as its high plasma protein adsorption resistance and anticoagulant activity, suggests a potential for blood-contacting applications.

During recent years, field-effect transistor biosensors (Bio-FET) for biomedical applications have experienced a robust development with evolutions in FET characteristics as well as modification of bio-receptor structures. This review initially provides contemplation on this progress by analyzing and summarizing remarkable studies on two aforementioned aspects. The former includes fabricating unprecedented nanostructures and employing novel materials for FET transducers whereas the latter primarily synthesizes compact molecules as bio-probes (antibody fragments and aptamers). Afterwards, a future perspective on research of FET-biosensors is also predicted depending on current situations as well as its great demand in clinical trials of disease diagnosis. From these points of view, FET-biosensors with infinite advantages are expected to continuously advance as one of the most promising tools for biomedical applications.

Biofouling on medical devices generally causes adverse complications, such as thrombosis, infection, and pathogenic calcification. Silicone is a widely used material for medical applications. Its surface modification typically encounters undesirable "hydrophobic recovery", leading to deterioration of surface engineering. In this study, we developed a stable superhydrophilic zwitterionic interface on polydimethylsiloxane (PDMS) elastomer by covalent silanization of sulfobetaine silane (SBSi) to resist nonspecific adsorption of bacteria, proteins, and lipids. SBSi is a zwitterionic organosilane assembly, enabling resisting surface reconstruction by forming a cross-linked network and polar segregation. Surface elemental composition was confirmed by X-ray photoelectron spectroscopy (XPS), and the long-term stability of modification was accessed using a contact angle goniometer. The biofouling tests were carried out by exposing substrates to bacterial, protein, and lipid solutions, revealing the excellent bioinertness of SBSi-tailored PDMS, even after 30 day storage in ambient. For the real-world application, we modified commercially available silicone hydrogel contact lenses with developed zwitterionic silane, presenting its antibacterial adhesion property. Moreover, the cytotoxicity of SBSi was accessed with NIH-3T3 fibroblast by the MTT assay, showing negligible cytotoxicity up to a concentration of 5 mM. Consequently, the strategy of surface engineering in this work can effectively retard the "hydrophobic recovery" occurrence and can be applied to other silicone-based medical devices in a facile way.

This work describes a novel tunable bioadhesive hydrogel of thermoresponsive N-isopropylacrylamide (NIPAAm) containing zwitterionic sulfobetaine methacrylate (SBMA). This novel hydrogel highly regulates general bioadhesive foulants through the adsorption of plasma proteins, the adhesion of human platelets and cells, and the attachment of bacteria. In this investigation, nonionic hydrogels of polyNIPAAm, zwitterionic hydrogels of polySBMA, and three copolymeric hydrogels of NIPAAm and SBMA (poly(NIPAAm-co-SBMA)) were prepared. The copolymeric hydrogels exhibited controllable temperature-dependent swelling behaviors and showed stimuli-responsive phase characteristics in the presence of salts. The interactions of these hydrogels with biomolecules and microorganisms were demonstrated by protein adsorption, cell adhesion, and bacterial attachment, which allowed us to evaluate their bioadhesive properties. An enzyme-linked immunosorbent assay (ELISA) with monoclonal antibodies was used to measure different plasma protein adsorptions on the prepared hydrogel surfaces. At a physiological temperature, the high content of the nonionic polyNIPAAm in poly(NIPAAm-co-SBMA) hydrogel exhibits a high protein adsorption due to the interfacial exposure of polyNIPAAm-rich hydrophobic domains. A relatively high content of polySBMA in poly(NIPAAm-co-SBMA) hydrogel exhibits reduced amounts of protein adsorption due to the interfacial hydration of polySBMA-rich hydrophilic segments. The attachment of platelets and the spreading of cells were only observed on polyNIPAAm-rich hydrogel surfaces. Interestingly, the incorporation of zwitterionic SBMA units into the polyNIPAAm gels was found to accelerate the hydration of the cell-cultured surfaces and resulted in more rapid cell detachment. Such copolymer gel surface was shown to be potentially useful for triggered cell detachment. In addition, the interactions of hydrogels with bacteria were also evaluated. The polySBMA-rich hydrogels exhibited evident antimicrobial properties when they were incubated with Gram-positive bacteria ( S. epidermidis ) and Gram-negative bacteria ( E. coli ). This work shows that the bioadhesive properties of poly(NIPAAm-co-SBMA) hydrogels can be effectively controlled via regulated nonionic and zwitterionic molar mass ratios. The tunable-bioadhesive behavior of temperature-sensitive poly(NIPAAm-co-SBMA) makes this biocompatible hydrogel appropriate for biomedical applications.

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