Collagen, the most abundant component of natural ECM, has attracted interest of scientific communities to replicate its multihierarchical self-assembling structure. Recent developments in collagen mimetic peptides were inclined toward the production of self-assembling short peptides capable of mimicking complex higher order structures with tunable mechanical properties. Here, we report for the first time, the crucial molecular design of oppositely charged collagen mimetic shortest bioactive pentapeptide sequences, as a minimalistic building block for development of next-generation biomaterials. Our rational design involves synthesis of two pentapeptides, where the fundamental molecular motif of collagen, that is, Gly-X-Y has been mutated at the central position with positively charged, lysine, and negatively charged, aspartate, residues. Depending on their overall surface charge, these peptides showed high propensity to form self-supporting hydrogel either at acidic or basic pH, which limits their biomedical applications. Interestingly, simple mixing of the two peptides was found to induce the coassembly of these designed peptides, which drives the formation of self-supporting hydrogel at physiological pH and thus enhanced the potential of exploring these peptides for biomedical purposes. This coassembly of ionic peptides was accompanied by the enhancement in the mechanical stiffness of the gels and reduction in overall zeta potential of the combined hydrogel, which provides the evidence for additional electrostatic interactions. Furthermore, the thixotropic nature of these gels offers an additional advantage of exploration of designer biomaterials as injectable gels. The nanofibers of coassembled hydrogel were found to be highly biocompatible to the fibroblast cells compared to the individual peptides, which was evident from their cytotoxicity studies. We anticipate that our rational design of ECM protein mimics in the form of short bioactive peptides will contribute significantly to the development of novel biomaterials and play a crucial role in the field of tissue engineering and regenerative medicines.

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Creating diverse nanostructures from a single gelator through modulating the self-assembly pathway has been gaining much attention in recent years. To this direction, we are exploring the effect of modulation of pH as a potential self-assembly pathway in governing the physicochemical properties of the final gel phase material. In this context, we used a classical nongelator with the ionic complementary sequence FEFK, which was rationally conjugated to an aromatic group naphthoxyacetic acid (Nap) at the N-terminal end to tune its gelation behavior. Interestingly, the presence of oppositely charged amino acids in the peptide amphiphile resulted in pH-responsive behavior, leading to the formation of hydrogels over a wide pH range (2.0–12.0); however, their structures differ significantly at the nanoscale. Thus, by simply manipulating the overall charge over the exposed surface of the peptide amphiphiles as a function of pH, we were able to access diverse self-assembled nanostructures within a single gelator domain. The charged state of the gelator at the extreme pH (2.0, 12.0) led to a thinner fiber formation, in contrast to the thicker fibers observed near the physiological pH owing to charge neutralization, thus promoting the lateral association. Such variation in molecular packing was found to be further reflected in the variable mechanical strengths of the peptide hydrogels obtained at different pH values. Moreover, the gelation of the peptide at physiological pH offers an additional advantage to explore this hydrogel as a cell culture scaffold. We anticipate that our study on controlling the self-assembly pathway of the ionic complementary peptide amphiphile can be an elegant approach to access diverse self-assembled materials, which can expand the zone of its applicability as a stimuli-responsive biomaterial.

We herein report the preparation and properties of the first polymer blend using pyrene functionalized polyaniline (pf-PANI). The pf-PANI has been synthesized and its blend has been prepared with the copolymer of vinylidene fluoride and hexafluoropropylene P(VDF-HFP). The FTIR results reveal intermolecular interaction between the polar amide group of pf-PANI and the polarized CH 2 group of P(VDF-HFP). The crystalline phase of PVDF of the copolymer revealed a transformation from a to b crystalline form after blending with pf-PANI, as found from FTIR and XRD measurements. The calorimetric measurements together with DMA results revealed the blend is partially miscible. The SEM measurements showed that the pf-PANI has been dispersed uniformly in the P(VDF-HFP) matrix. The solution photoluminescence spectrum of the pf-PANI exhibited emission in the purple-blue region and is slightly red shifted for the blend. The possible applications of this flexible fluorescent pf-PANI/P(VDF-HFP) has been suggested.

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.