Functionalizable and nonfouling zwitterionic carboxybetaine hydrogels with a carboxybetaine dimethacrylate crosslinker

We have introduced a dimethacrylate carboxybetaine-based crosslinker that has excellent compatibility with zwitterionic hydrogel systems. Poly(carboxybetaine methacrylate) (pCBMA) hydrogels prepared with the new CBMA crosslinker (CBMAX) result in considerably improved solubility, homogeneity, and mechanical properties (up to 8 MPa compressive modulus) over those prepared with the commercially available N,N'-methylenebis(acrylamide) (MBAA) crosslinker. The zwitterionic nature of the CBMAX crosslinker provides continuity of ordered hydration in the CBMA hydrogel and retains its nonfouling properties. CBMAX-crosslinked CBMA hydrogels had lower cell fouling than MBAA-crosslinked CBMA hydrogels and in fact reduced cell adhesion by about 90% relative to pHEMA hydrogels. Furthermore, unlike pHEMA, CBMA hydrogels are readily functionalizable. Cell adhesion on nonfouling CBMA hydrogels was controlled by cRGD functionalization.