Hierarchical non-covalent interactions in bioinspired peptide-polymer hydrogels and composite networks
Date
2025
Authors
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Publisher
University of Delaware
Abstract
Nature uses physically assembled, hierarchical structures to achieve materials with impressive mechanical properties and responsive functions. Inspired by natural materials that harness interactions of polypeptides to dictate properties such as modulus, toughness, and morphology, this dissertation has implemented multiple strategies to control hierarchical assembly in polymeric hydrogels. Specifically, polypeptide motifs were incorporated into polymer architectures to drive assembly and performance in polymer hydrogels, targeting potential applications in injectable biomaterials and responsive networks. Non-covalent interactions between building blocks of peptide-polymer hydrogels were modulated via multiple pathways, resulting in hydrogels with tunable properties. ☐ First, we examine the impact of peptide motifs poly(e-carbobenzyloxy-L-lysine) and poly(b-benzyl-L-aspartate) in poly(ethylene glycol) (PEG)-based polyureas on polymer hydrogelation and performance. These peptide-polyurea hybrids demonstrated rapid gelation upon addition of water driven by hierarchical assembly of peptide segments in species containing α-helical secondary structures. The mechanical strength of these peptide-polyurea hydrogels could be controlled by altering peptide segment length, and was largely maintained over a wide temperature range from 10- 80 °C. Furthermore, these physically assembled hydrogels demonstrated impressive shear recovery properties, in which the peptide-polyurea network could be recovered within 10 s after shear disruption. This research demonstrated the utility of peptide-polyureas as a robust, dynamic hydrogel platform. ☐ Next, these initial findings were extended through the addition of hydrogen-bonding nanofillers to further modulate the non-covalent interactions of peptide-polyurea hydrogels. Cellulose nanocrystals (CNCs) were incorporated into peptide polyurea hydrogels at various loadings to tailor key hydrogel properties via matrix-filler interactions. The mechanical reinforcement of peptide-polyurea hydrogels was shown to be dependent on both CNC loading and peptide segment length, with storage modulus increasing up to 1825%. Inclusion of CNCs also resulted in temperature-driven stiffening transitions, as well as shifts in the conformations of peptidic domains (α-helices or β-sheets). Nanofiller-matrix interactions also were shown to facilitate network reformation under shear, highlighting the potential for these nanocomposite hydrogels to serve as high-performance injectable materials. This work demonstrates that peptide-CNC interactions can be harnessed to improve the performance of non-covalently assembled, peptide-polymer hydrogels. ☐ Finally, multi-chain, peptide coiled-coil assemblies (bundlemers) were covalently incorporated into a hydrogel network. Alkene reactive sites were placed at controlled positions of the bundlemer sequence, allowing for photopolymerization with PEG diacrylate, resulting in crosslinked bundlemer-PEG hydrogel networks. The sequence position of reactive handles, as well as solution conditions, impacted polymerization kinetics and hydrogel mechanics. Liquid crystalline (LC) assembly formed by association of bundler peptides was achieved. Additionally, the application of shear force during polymerization was shown to drive increased LC formation and alignment in the hybrid hydrogels. Furthermore, it was demonstrated that changes in pH drove disruption of bundlemer LCs, thus revealing the potential for bundlemer-polymer hybrids to display stimuli-responsive behavior. ☐ Overall, this dissertation demonstrates multiple strategies to control non-covalent interactions in peptide-polymer hybrid hydrogels. Through synthetic control over peptide-polymer architectures, tailored matrix-filler interactions, and processing of hydrogel materials, hierarchical self-assembly in these platforms can be harnessed to achieve improved performance of polymeric hydrogels.
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Keywords
Bioinspired, Hydrogels, Polymers, Polypeptides, Cellulose nanocrystals