Micropatterning of bioactive heparin-based hydrogels

Abstract

This paper describes a UV photopatterning of bioactive heparin-based hydrogels on glass substrates. In this approach, hydrogel micropatterns were formed by UV-initiated thiol-ene reaction between thiolated heparin and diacrylated poly(ethylene) glycol (PEG-DA). Analysis of gelation kinetics showed that photo-crosslinked hydrogels formed faster and were stronger when compared to hydrogels formed by competing Michael addition reaction. To highlight bioactivity of heparin-PEG hybrid gels, hepatocyte growth factor (HGF) was mixed into prepolymer solution prior to hydrogel patterning. Immunostaining showed that HGF was retained after 5 days in the hybrid heparin-PEG hydrogel microstructures but was rapidly released from pure PEG gel microstructures. In a set of experiments further highlighting bioactivity of microfabricated heparin-based hydrogel, primary rat hepatocytes were cultured next to heparin and pure PEG hydrogel disks (similar to 500 mu m in diameter). ELISA analysis revealed that hepatocytes residing next to heparin-based hydrogels were producing similar to 4 times more albumin at day 7 compared to cells cultured next to inert PEG hydrogels. In the future, microfabricated heparin-based hydrogels described in this paper will be employed for designing cellular microenvironment in vitro and as vehicles for cell transplantation in vivo.