Nonfouling Hydrogels Formed from Charged Monomer Subunits

Abstract

A critical challenge in the field of biomaterials is the often undesirable, but immediate, coating of implants with nonspecifically adsorbed proteins upon contact with bodily fluids. Prior research has shown that overall neutral materials containing a homologous arrangement of mixed charges exhibit nonfouling properties. This has been widely demonstrated for zwitterionic materials and more recently for coatings containing an equimolar mixture of positively and negatively charged monomer subunits. In this investigation it is demonstrated that nonfouling hydrogels can be formed through this approach, and the physical properties of the resulting materials are thoroughly characterized. In particular, hydrogels were formed from mixtures of [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TM) and 3-sulfopropyl methacrylate potassium salt (SA) monomers with varying concentrations of a triethylene glycol dimethacrylate (TEGDMA) cross-linker. The swelling, weight percentage water, surface zeta potential, and compressional properties of the gels were characterized, and the nonfouling properties were demonstrated using enzyme-linked immunosorbant assays for both negatively charged fibrinogen and positively charged lysozyme. The results confirm that the TM:SA hydrogel systems have nonfouling properties that are equivalent to established nonfouling controls. Additionally, even though the gels were resistant to nonspecific protein adsorption, a composition analysis suggests that there is room to further improve the nonfouling performance because there is a slight enrichment of the SA monomer relative to the TM monomer.

Recent biomedical advances with polyampholyte polymers

“…It was also noted that by lowering the ionic strength of the protein adsorption solution, the protein adsorption levels were increased slightly on negatively charged hydrogels (∼5% increase) and greatly on positively charged hydrogels (∼50%). In a more recent study, Dobbins et al further examined the properties of hydrogels synthesized with a 1 : 1 molar ratio of TM and SA and various amounts of TEGDMA as a cross‐linking agent . In this study, it was demonstrated that the mechanical properties of the hydrogel could be easily adjusted without impacting the nonfouling properties.…”

“…In addition to their high levels of hydration and general biocompatibility, it is possible to tailor the mechanical properties of polyampholyte polymer hydrogels through monomer selection criteria. Furthermore, polyampholyte hydrogels have also been demonstrated to have resistance to nonspecific protein adsorption . It has been hypothesized that this property will lead to an improved wound healing response, by reducing the foreign body reaction to the implanted biomaterial.…”

Achieving low-fouling surfaces with oppositely charged polysaccharides via LBL assembly

“…CB-based polymers have additional features of charge-switching and functionalization [10]. Furthermore, it has been demonstrated that self-assembled monolayers (SAMs), copolymers or hydrogels including peptides containing a certain ratio of mixed positively and negatively charged monomer subunits exhibit nonfouling properties [11][12][13][14][15][16]. Based on these results and the mechanism of zwitterionic materials, it is possible to prepare a new nonfouling surface by balancing the net charge and dipole of a mixture of oppositely charged polyelectrolytes deposited on a surface.…”

Bioinspired Pseudozwitterionic Hydrogels with Bioactive Enzyme Immobilization via pH-Responsive Regulation

“…Compared to other mixed-charge systems, the zeta potential within ±10 mV can be considered to be antifouling. 23,29 With a zeta potential at ∼ −10 mV, the closest example would be SA5/DMAEMA5 as mentioned in the investigation conducted by Venault et al 26 Hemolysis and Clotting Time Assay. In order to apply the hydrogel materials in biomedical engineering, it is necessary to test the biocomparability of hydrogels against blood cells because inflammatory responses may follow hemolysis and clotting caused by inappropriate chemistry on the material surface.…”