Myocardial matrix–polyethylene glycol hybrid hydrogels for tissue engineering

Abstract

Similar to other protein-based hydrogels, extracellular matrix (ECM) based hydrogels, derived from decellularized tissues, have a narrow range of mechanical properties and are rapidly degraded. These hydrogels contain natural cellular adhesion sites, form nanofibrous networks similar to native ECM, and are biodegradable. In this study, we expand the properties of these types of materials by incorporating poly(ethylene glycol) (PEG) into the ECM network. We use decellularized myocardial matrix as an example of a tissue specific ECM derived hydrogel. Myocardial matrix–PEG hybrids were synthesized by two different methods, cross-linking the proteins with an amine-reactive PEG-star and photo-induced radical polymerization of two different multi-armed PEG-acrylates. We show that both methods allow for conjugation of PEG to the myocardial matrix by gel electrophoresis and infrared spectroscopy. Scanning electron microscopy demonstrated that the hybrid materials still contain a nanofibrous network similar to unmodified myocardial matrix and that the fiber diameter is changed by the method of PEG incorporation and PEG molecular weight. PEG conjugation also decreased the rate of enzymatic degradation in vitro, and increased material stiffness. Hybrids synthesized with amine-reactive PEG had gelation rates of 30 min, similar to the unmodified myocardial matrix, and incorporation of PEG did not prevent cell adhesion and migration through the hydrogels, thus offering the possibility to have an injectable ECM hydrogel that degrades more slowly in vivo. The photo-polymerized radical systems gelled in 4 min upon irradiation, allowing 3D encapsulation and culture of cells, unlike the soft unmodified myocardial matrix. This work demonstrates that PEG incorporation into ECM-based hydrogels can expand material properties, thereby opening up new possibilities for in vitro and in vivo applications.