Gelatin/Albumin-Based Hydrogels Scaffolds By Two-Photon Polymerization

Abstract

Developing 3D hydrogel scaffolds capable of promoting cell viability and important cell-extracellular matrix (ECM) interactions is of great importance for Tissue Engineering (TE) applications. To mimic the biochemical and structural complexity of ECM, two-photon polymerization (2PP) shows great promise to fabricate ECM-biomimetic hydrogels because it allows the fabrication of complex user-dictated shapes with micrometer-scale resolution. Poly(ethylene glycol) diacrylates (PEGDA) have been widely used for 2PP fabrication of hydrogels due to their high reactivity. However, the residues of PEGDA and unreacted acrylate groups are potentially cytotoxic. For most TE applications, monomers with low cytotoxicity are in demand. Our previous work proved that vinyl esters (VEs) are much less cytotoxic than their (meth)acrylates references. Although VEs are generally not as reactive as acrylates, the thiol-vinyl ester photo-click reactions are robust enough for efficient 2PP applications. Since it is hard to assemble ECM-biomimetic hydrogels using synthetic monomers alone, proteins with thiol and VE functionalities were prepared for use in thiol-ene photo-click hydrogels. Presented are the synthesis of vinyl ester derivatives of gelatin hydrolysate, reductive disulfide cleavage of bovine serum albumin, and 2PP fabrication of gelatin/albumin based hydrogel scaffolds using novel water soluble 2PP initiators. The vinyl ester modified gelatin/albumin mixture could be photopatterned at high writing speed and low laser power providing high resolution microstructures. Acknowledgement. The support by the China Scholarship Council (CSC No. 2009688014) and the European Commission in the framework of Marie Curie IEF (project VINDOBONA, No. 297895) is gratefully acknowledged.