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

Abstract

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., β-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.

Designing Cardin-Motif Peptide and Heparin-Based Multicomponent Advanced Bioactive Hydrogel Scaffolds to Control Cellular Behavior

“…Alamar Blue, a specific fluorescence indicating dye, is used to assess cellular proliferation on the composite hydrogel in different time periods. , The detail study is reported in our earlier literatures. ,, Cellular proliferation was carried out at different intervals of 48, 72, and 120 h. In particular, triplicate studies of this experiment were done to get the averaged data which can be represented as mean ± SD.…”

“…47,48 The detail study is reported in our earlier literatures. 11,21,48 Cellular proliferation was carried out at different intervals of 48, 72, and 120 h. In particular, triplicate studies of this experiment were done to get the averaged data which can be represented as mean ± SD.…”

“…20 Recently, it has been demonstrated that after introducing carbohydrate moieties with peptides, the bioavailability and morphological properties of the peptide has been improved. 21 In this direction, several reports have shown that the attachment of the glucosamine to peptides can enhance wound healing capacity, antimicrobial activity, 22 and also inhibit scar formation. 23 Specifically, Xu et al have investigated the role of covalent modulation of glucosamine with the hydrophobic group of peptides to further induce hydrogel formation that promoted wound healing and prevented the scar formation in the mice model.…”

“…In this direction, sugar and peptide-based bioinspired composite scaffolds are particularly interesting candidates as they resonate well to match the cellular microenvironment and thus hold potential to communicate with the cells by providing essential biological signals to promote cellular behavior in the native ECM. , Most importantly, it is evident that the natural coexistence of sugars and peptides can initiate crucial molecular interactions between these two important counterparts of the native ECM which is well-known to form important functional as well as biologically relevant macromolecular machineries, such as proteins, glycoproteins, etc . Recently, it has been demonstrated that after introducing carbohydrate moieties with peptides, the bioavailability and morphological properties of the peptide has been improved . In this direction, several reports have shown that the attachment of the glucosamine to peptides can enhance wound healing capacity, antimicrobial activity, and also inhibit scar formation .…”

Stereogenic Harmony Fabricated Mechanoresponsive Homochiral Triphenylalanine Analogues with Synergistic Antibacterial Performances: A Potential Weapon for Dermal Wound Management

“…Hydrogelators comprising peptides constitute a key element in the central dogma of global health care avenues. − The impressive amalgamation of properties such as biodegradability, biocompatibility, low cytotoxicity, and ability to mimic natural proteins makes them remarkable candidates for the design of advanced synthons with diversified applicabilities like drug delivery, tissue engineering, effluent management, antimicrobial, wound dressing, and many more. − …”