(594a) Functionalizable Carboxybetaine Hydrogels with a Novel Carboxybetaine Dimethacyrlate Crosslinker

Hydrophilic crosslinked polymer networks, or hydrogels, are commonly studied systems for many biological applications ranging from corneal implants to drug delivery and wound dressings. The key attributes of hydrogels that make them particularly well-suited to biological applications are their high water content, biological stability, optical transparency, permeability to metabolites, and sufficient crosslinking to prevent dissolution. Poly(2-hydroxyethyl methacrylate) (pHEMA) has emerged as the leading hydrogel candidate for most biological applications, especially implants and tissue engineering scaffolds, due to its chemical stability and mechanical integrity. In order to expand the scope of hydrogels' impact in the biomedical arena, several challenges must be addressed, primarily improving mechanical properties, without reducing its beneficial properties. Currently, water content and permeability come at the expense of mechanical strength, and are limited by crosslinkers with low water solubility. Hydrogels made from zwitterionic materials have many interesting properties. Zwitterionic hydrogels have been studied as superabsorbants, with particular attention being paid to their swelling properties. We have previously reported low protein adhesion on sulfobetaine methacrylate and mixed charge hydrogels and low cell adhesion on carboxybetain methacrylate gels. The zwitterionic gels studied so far have shown low mechanical strength, which limits their potential biological uses. Part of the problem, we believe, is the dearth of available crosslinkers that are truly water soluble. We designed and synthesized a hydrophilic dimethacrylate carboxybetaine-based crosslinker as an alternative to the commercially available but inadequate N,N'-methylenebis(acrylamide) (MBAA). Poly(carboxybetaine methacrylate) (pCBMA) hydrogels are able to incorporate the new CBMA crosslinker (CBMAX) much more efficiently than the MBAA crosslinker, resulting in hydrogels with considerably improved solubility, homogeneity and mechanical properties (up to 8 MPa compressive modulus). Furthermore, the zwitterionic nature of the new CBMAX crosslinker provides continuity of hydration in the CBMA hydrogel, to retain the nonfouling properties of these materials. 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, a material whose biocompatibility is well-known. Unlike pHEMA, however, CBMA hydrogels are functionalizable; cell adhesion on nonfouling CBMA hydrogels was controlled with cRGD functionalization.