Influence of Network Topology on the Viscoelastic Properties of Dynamically Crosslinked Hydrogels

Abstract

<jats:p>Biological materials combine stress relaxation and self-healing with non-linear stress-strain responses. These characteristic features are a direct result of hierarchical self-assembly, which often results in fiber-like architectures. Even though structural knowledge is rapidly increasing, it has remained a challenge to establish relationships between microscopic and macroscopic structure and function. Here, we focus on understanding how network topology determines the viscoelastic properties, i.e. stress relaxation, of biomimetic hydrogels. We have dynamically crosslinked two different synthetic polymers with one and the same crosslink. The first polymer, a polyisocyanopeptide (PIC), self-assembles into semi-flexible, fiber-like bundles and thus displays stress-stiffening, similar to many biopolymer networks. The second polymer, 4-arm poly(ethylene glycol) (starPEG), serves as a reference network with well-characterized structural and viscoelastic properties. Using one and the same coiled coil crosslink allows us to decouple the effects of crosslink kinetics and network topology on the stress relaxation behavior of the resulting hydrogel networks. We show that the fiber-containing PIC network displays a relaxation time approximately two orders of magnitude slower than the starPEG network. This reveals that crosslink kinetics is not the only determinant for stress relaxation. Instead, we propose that the different network topologies determine the ability of elastically active network chains to relax stress. In the starPEG network, each elastically active chain contains exactly one crosslink. In the absence of entanglements, crosslink dissociation thus relaxes the entire chain. In contrast, each polymer is crosslinked to the fiber bundle in multiple positions in the PIC hydrogel. The dissociation of a single crosslink is thus not sufficient for chain relaxation. This suggests that tuning the number of crosslinks per elastically active chain in combination with crosslink kinetics is a powerful design principle for tuning stress relaxation in polymeric materials. The presence of a higher number of crosslinks per elastically active chain thus yields materials with a slow macroscopic relaxation time but fast dynamics at the microscopic level. Using this principle for the design of synthetic cell culture matrices will yield materials with excellent long-term stability combined with the ability to locally reorganize, thus facilitating cell motility, spreading and growth.</jats:p>

Network Growth and Structural Characteristics of Globular Protein Hydrogels

“…Nevertheless, we see that the number of available cross-link sites is the determining factor in the overall average cross-link coordination throughout the network. This qualitatively corresponds to experiments performed by Grad et al in that our monomers can also be microscopically designed to alter the network topology to some extent.…”

“…Importantly for this work, Grad et al were recently able to design highly specific network building blocks to show that in addition to the cross-linking kinetics, the network topology of a hydrogel affects its stress relaxation capabilities . Although Grad et al used intermediate coiled coils as cross-links between polymer chains, other methods of cross-linking are available, such as direct covalent cross-links or physical interactions. , Nevertheless, their work implies that microscopic connectivity limits on cross-linking can also translate to the macroscale.…”

Semiflexible polymer scaffolds: an overview of conjugation strategies

“…275 The advantages of this approach has been demonstrated in DNA functionalized PNIPAM nanogels in the context of controlled Dox release. 276 Furthermore, Grad et al recently developed a wsPCIP hydrogel with tunable mechanical properties via a similar crosslinking method as described above, using coiled coils as crosslinks instead of DNA, 277 clearly demonstrating the potential of the use of functional crosslinks.…”

Pyrene-Based Macrocrosslinkers with Supramolecular Mechanochromism for Elastic Deformation Sensing in Hydrogel Networks

“…Unlike randomly crosslinked networks, sPEG hydrogels evenly distribute applied mechanical loads on all bonds and dissipate mechanical energy by controlled uncoiling 30 of the network segments. 31 – 35 This renders any detection of force-induced events using optical force probes 36 based on covalent bond scission difficult and hence serves as an ideal proof-of-concept application for our mechanochromic macrocrosslinkers. We show that PyMC endows the sPEG hydrogels with reversible mechanochromic behavior in the elastic deformation regime.…”