Designing a Tenascin-C-Inspired Short Bioactive Peptide Scaffold to Direct and Control Cellular Behavior

Over the last decade, synthetically designed scaffolds are emerging as promising biomaterials for tissue engineering applications. In this context, peptide hydrogels are gaining wide attention, owing to their ability to mimic structural and functional complexity of the natural extracellular matrix (ECM). To this end, exploration of minimalistic bioactive peptide sequences for the fabrication of tissue engineering scaffolds provides a competitive edge over the conventional design principles where complex sequences were mainly explored for scaffold formation. In the present study, we explored the self-assembling potential of minimalistic bioactive peptide sequence from tenascin-C protein and its application in supporting cellular viability and proliferation. Tenascin-C is a multimeric protein known to express in adult tissues mainly during tissue injury or remodeling. To the best of our knowledge, the designed octapeptide is the shortest bioactive sequence derived solely from tenascin-C, which is known in the literature to impart specific bioactivity. The short peptide sequence showed high propensity to form a nanofibrous network at physiological pH, which was further entangled to form a macroscopic hydrogel network. Interestingly, the gels were found to be mechanoresponsive and thixotropic which opens up the scope for utilizing them as designer injectable matrices. These novel hydrogels supported the growth and proliferation of cells of both neural and non-neural ECM origin. However, neural cells cultured on these bioactive hydrogels showed normal β-III tubulin expression, highlighting their specific potential to be further explored for tissue engineering applications.