PEG-based bioactive hydrogels crosslinked via phosphopantetheinyl transferase

State-of-the-art tissue engineering strategies increasingly rely on the performance of bioactive hydrogels formed via cell-friendly crosslinking reactions. Enzymatic reactions possess ideal characteristics for such applications, but they are currently still underexplored in biomaterials design. Here we report the development of hybrid bioactive hydrogels formed via a posttranslational modification reaction using phosphopantetheinyl transferase (PPTase). PPTase was shown to catalyze the covalent crosslinking of CoenzymeA-functionalized poly(ethylene glycol) (PEG) multiarm macromers and recombinantly produced acyl carrier protein (ACP) dimers. Crosslinking kinetics and physicochemical properties of PPTase hydrogels were characterized. Proof-of-principle experiments demonstrate the successful covalent bio-functionalization of gels with a CoA-derivatized cell adhesion peptide. Polymerization of gels in the presence of primary mammalian cells was shown to result in no loss in cell viability compared to a well established, chemically crosslinked gel system.