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 (∼500 µm in diameter). ELISA analysis revealed that hepatocytes residing next to heparin-based hydrogels were producing ∼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.