(255ah) Zwitterion-Poly(ethylene glycol) Hydrogels Prevent Bacterial Adhesion

Kolewe, K. W., University of Massachusetts Amherst
Emrick, T., University of Massachusetts Amherst
Schiffman, J. D., University of Massachusetts Amherst
Developing strategies that delay and/or prevent the onset of biofilm formation without inducing evolutionary resistance of bacteria is a pressing challenge. While commercial antimicrobial agents and metallic nanoparticles have been proven effective at inactivating microorganisms, their overuse has led to the spread of antibiotic resistance. An alternative approach would be to fundamentally understand how intrinsic materials properties influence bacterial adhesion in order to improve the design of antifouling materials. We have demonstrated a statistically relevant correlation between hydrogel stiffness and bacterial adhesion. â??Softâ? and â??stiffâ? model poly(ethylene glycol) (PEG) hydrogels were synthesized that had Youngâ??s moduli of 44 and 6,500 kPa, respectively. When challenged with the Gram-negative microbe Escherichia coli, the â??softâ? PEG hydrogels exhibited a 15 fold reduction in biofouling than the â??stiffâ? PEG hydrogels. Likely, this resulted because key cellular processes, including surface adhesion, are modulated in response to substrate stiffness, an intrinsic property of all materials. This phenomena, that fewer bacteria adhered to softer hydrogels, was also observed for a Gram-positive bacterial species, Staphylococcus aureus. Further, this relationship was observed to occur independent of chemistry as mechanically similar agar hydrogels displayed the same correlation, suggesting that mechanical sensitivity should be factored into antifouling materials design. However, in order to withstand operational pressures, most medical devices are developed to be stiff, therefore, we developed a method to incorporate a zwitterionic polymer into the fully swollen hydrogels to improve antifouling performance. Through the distribution of positive and negative charges on individual polymer segments, zwitterionic polybetaines form a hydration shell that imparts strong fouling resistivity. Polymerization of a phoshobetaine zwitterionic polymer, poly(2-methacryloyloxyethyl phosphorylcholine) with polydopamine into the PEG-based hydrogels substantially enhanced the antifouling performance of all tested hydrogels. The stiff zwitterionic-PEG hydrogels exhibited the greatest improvement, after 24 hrs, ~90% less E. coli and S. aureus adhered to the hydrogels compared to the PEG only hydrogels. These results suggest that a fundamental structure-property relationship can be used synergistically with zwitterionic polymers to further improve the fouling resistance of PEG-based hydrogels.