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™) 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™ self-assembled peptide was combined with the thermosensitive HA to produce a series of injectable thermoresponsive IPNs. The HA-Puramatrix™ 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.
Highlights
Stroke is a degenerative injury of the central nervous system (CNS) and is one of the major causes of longterm disabilities in humans as well as the third largest cause of death in the world [1]
To achieve a successful and functional scaffold for tissue engineering, physical properties such as morphology, porosity, swelling ratio, degradation rate and mechanical properties such as rheological behavior and cellular behavior should match the requirements for regenerating tissue in the intended application
Adding Puramatrix to hyaluronic acid (HA)-1 has been shown to change the structure of the hydrogel to that of an aligned porous structure with less swelling ratio in both phosphate-buffered saline (PBS) and medium, which can be effective in directing the migration and growth of the neural cells
Summary
Stroke is a degenerative injury of the central nervous system (CNS) and is one of the major causes of longterm disabilities in humans as well as the third largest cause of death in the world [1]. By grafting neural stem cells to the CNS it may be possible to treat stroke. Using stem cells often requires a three-dimensional scaffold for attachment and to provide an appropriate environment for cell survival and differentiation. Hydrogel scaffolds have been shown to be a good physiological model of the extracellular matrix, and they are good candidates for encapsulating neural cells since they can be modified to have structural, mechanical and degradation properties similar to biological tissues. Hydrogels that consist of only one polymer are normally not able to provide the mechanical and biological characteristics required for tissue engineering purposes. Researchers were able to resolve brain tissue engineering-related difficulties by designing and synthesizing IPNs using different polymers with tunable physical, biochemical and mechanical properties based on the requirements of the regeneration progress [9]
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