Biomimetic strain-stiffening in fully synthetic dynamic-covalent hydrogel networks

Abstract

Strain-stiffening is observed and characterized in flexible PEG hydrogel networks crosslinked via dynamic-covalent boronate ester bonds, revealing an uncommon synthetic mimic of a mechanoresponse found in natural biopolymer networks.

Well-defined synthetic copolymers with pendent aldehydes form biocompatible strain-stiffening hydrogels and enable competitive ligand displacement

“…61 Recently, strain-stiffening hydrogels from synthetic, flexible polymers using DCvC for network junctions were reported using dynamic covalent imine formation, 71 and boronate ester crosslinking . 49 However, the strain-stiffening behavior reported in these systems did not follow the expected trend; instead of exhibiting an increase in stiffening index at higher polymer concentrations, a decrease was observed. We found the same trend in our imine-based copolymer hydrogels (Figure 4D, S24 & S25).…”

“…72,73 Webber et al recently studied this unexpected strain-stiffening behavior in boronate ester hydrogels, and they propose a hybrid strain-stiffening mechanism arising from a combination of both entropic and enthalpic (bond deformation) contributions. 49 To understand more about the relationship between flexible dynamic covalent networks and strain-stiffening behavior, hydrogel systems including those reported herein will be a necessary tool, while also holding promise for mimicking the strain-stiffening behavior present in native ECM for biomedical applications.…”

“…These copolymers crosslink rapidly, and exhibit strain-stiffening behavior, which has only been observed in few synthetic systems. [49][50][51] Using the reversible nature of the dynamic covalent bonds, we demonstrated competitive ligand displacement via fluorescence resonance energy transfer (FRET) (Figure 1, right). These synthetic hydrogels also display excellent https://doi.org/10.26434/chemrxiv-2024-n9p8h ORCID: https://orcid.org/0000-0002-5289-3491 Content not peer-reviewed by ChemRxiv.…”

Nonlinear Elastic Bottlebrush Polymer Hydrogels Modulate Actomyosin Mediated Protrusion Formation in Mesenchymal Stromal Cells

“…The strain-stiffening mechanics of the hydrogels were measured directly after network formation ( equilibrium / in situ scaling, Table S3) and plotted as oscillation stress versus strain ( Figure 2a ). The strain-stiffening properties of the bottlebrush scaffolds can be attributed to the high M e of the SH-PPEGA9- N bb -SH, which only need to be stretched a small amount to reach complete network extension and the onset of stiffening compared to linear PEG dithiols as illustrated in Figure 2b [30] . When the differential modulus, K’equil , is plotted as a function of σ equil to visualize the onset of strain-stiffening (σ c , equil ), we observe that σ c , equil of the bottlebrush hydrogels is always lower than the moduli-matched PEG-2k, 2.5 and 3.5 wt% controls.…”

Managing Diabetes with Hydrogel Drug Delivery

“…Subsequent work on this platform explored the significance of experimental parameters such as pH, pK a , K eq , and association/dissociation kinetics on the formation and function of these PEG-based hydrogels. [172][173][174][175] In the vast majority of systems, glucose-responsive release of insulin was largely suboptimal due to limited acceleration in release upon elevated glucose conditions as well as insulin leakage when not needed; indeed, in spite of many studies on this general class of materials, in vivo functional studies have been rarely included in assessing any of these platforms.…”