An aligned fibrous and thermosensitive hyaluronic acid-puramatrix interpenetrating polymer network hydrogel with mechanical properties adjusted for neural tissue

Abstract

Central nervous system (CNS) injuries such as stroke or trauma can lead to long-lasting disability, and there is no currently accepted treatment to regenerate functional CNS tissue after injury. Hydrogels can mimic the neural extracellular matrix by providing a suitable 3D structure and mechanical properties and have shown great promise in CNS tissue regeneration. Here we present successful synthesis of a thermosensitive hyaluronic acid-RADA 16 (Puramatrix (TM)) peptide interpenetrating network (IPN) that can be applied in situ by injection. Thermosensitive hyaluronic acid (HA) was first synthesized by combining HA with poly(N-isopropylacrylamide). Then, the Puramatrix (TM) self-assembled peptide was combined with the thermosensitive HA to produce a series of injectable thermoresponsive IPNs. The HA-Puramatrix (TM) IPNs formed hydrogels successfully at physiological temperature. Characterization by SEM, rheological measurements, enzymatic degradation and swelling tests was performed to select the IPN optimized for neurologic use. SEM images of the optimized dry IPNs demonstrated an aligned porous structure, and the rheological measurements showed that the hydrogels were elastic, with an elastic modulus of approximately 500 Pa, similar to that of brain tissue. An evaluation of the cell-material interactions also showed that the IPN had biological characteristics required for tissue engineering, strongly suggesting that the IPN hydrogel possessed properties beneficial for regeneration of brain tissue.