Exploring the TEMPO-Oxidized Nanofibrillar Cellulose and Short Ionic-Complementary Peptide Composite Hydrogel as Biofunctional Cellular Scaffolds.

Multicomponent self-assembly is an emerging approach in peptide nanotechnology to develop nanomaterials with superior physical and biological properties. Inspired by the multicomponent nature of the native extracellular matrix (ECM) and the well-established advantages of co-assembly in the field of nanotechnology, we have attempted to explore the noncovalent interactions among the sugar and peptide-based biomolecular building blocks as an approach to design and develop advanced tissue scaffolds. We utilized TEMPO-oxidized nanofibrillar cellulose (TO-NFC) and a short ionic complementary peptide, Nap-FEFK, to fabricate highly tunable supramolecular hydrogels. The differential doping of the peptide into the TO-NFC hydrogel was observed to tune the surface hydrophobicity, microporosity, and mechanical stiffness of the scaffold. Interestingly, a differential cellular response was observed toward composite scaffolds with a variable ratio of TO-NFC versus Nap-FEFK. Composite scaffolds having a 10:1 (w/w) ratio of TO-NFC and the Nap-FEFK peptide showed enhanced cellular survival and proliferation under two-dimensional cell culture conditions. More interestingly, the cellular proliferation on the 10:1 matrix was found to be similar to that of Matrigel in three-dimensional culture conditions, which clearly indicated the potential of these hydrogels in advanced tissue engineering applications. Additionally, these composite hydrogels did not elicit any significant inflammatory response in Raw cells and supported their survival and proliferation, which further emphasized their ability to form versatile scaffolds for tissue regeneration. This multicomponent assembly approach to construct biomolecular composite hydrogels to access superior physical and biological properties within the scaffold is expected to improve the scope for designing novel ECM-mimicking biomaterials for regenerative medicine.