Exploring Supramolecular Interactions between the Extracellular-Matrix-Derived Minimalist Bioactive Peptide and Nanofibrillar Cellulose for the Development of an Advanced Biomolecular Scaffold.

It has been increasingly evident over the last few years that bioactive peptide hydrogels in conjugation with polymer hydrogels are emerging as a new class of supramolecular materials suitable for various biomedical applications owing to their specificity, tunability, and nontoxicity toward the biological system. Despite their unique biocompatible features, both polymer- and peptide-based scaffolds suffer from certain limitations, which restrict their use toward developing efficient matrices for controlling cellular behavior. The peptide hydrogels usually form soft matrices with low mechanical strength, whereas most of the polymer hydrogels lack biofunctionality. In this direction, combining polymers with peptides to develop a conjugate hydrogel can be explored as an emergent approach to overcome the limitations of the individual components. The polymer will provide high mechanical strength, whereas the biofunctionality of the material can be induced by the bioactive peptide sequence. In this study, we utilized TEMPO-oxidized nanofibrillar cellulose as the polymer counterpart, which was co-assembled with a short N-cadherin mimetic bioactive peptide sequence, Nap-HAVDI, to fabricate an NFC-peptide conjugate hydrogel. Interestingly, the mechanical strength of the peptide hydrogel was found to be significantly improved by combining the peptide with the NFC in the conjugate hydrogel. The addition of the peptide into the NFC also reduced the pore size within NFC matrices, which further helped in improving cellular adhesion, survival, and proliferation. Furthermore, the cells grown on the NFC and NFC-peptide hybrid hydrogel demonstrated normal expression of cytoskeleton proteins, i.e., ß-tubulin in C6 cells and actin in L929 cells, respectively. The selective response of neuronal cells toward the specific bioactive peptide was further observed through a protein expression study. Thus, our study demonstrated the collective role of the cellulose-peptide composite material that revealed superior physical properties and biological response of this composite scaffold, which may open up a new platform for biomedical applications.

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.