Dynamically Restructuring Hydrogel Networks Formed with Reversible Covalent Crosslinks

Abstract

Nature provides many examples of soft gel-like materials where performance is determined by tuning time-dependent mechanical properties with dynamic bonding interactions between biomacromolecules.[1] Accordingly, synthetic gels that contain dynamic bonding interactions have undergone intense investigation in fundamental and applied material science. The balance of solid-like and fluid-like behavior in these gel networks results from the binding equilibrium of reversible crosslinks between polymer chains. [2][3][4][5] Contemporary research on gels has focused on self-assembled systems [6][7][8][9][10][11][12][13][14][15] usually exploiting hydrogen bonding interactions. However, gels crosslinked with reversible covalent bonding chemistries [16][17][18] would provide an energetically favorable, [19] specific and controlled mechanism for engineering functional dynamic networks. [20][21][22][23][24] We have synthesized hydrogel networks that form in the physiological pH range by the reversible covalent interaction of polymer-bound phenylboronic acid and salicylhydroxamic acid (Fig. 1). These gels demonstrate a spectrum of pH-dependent viscoelastic behavior that can be controlled by the chemical composition of the polymer backbone. Moreover, the reversible crosslinks allow these networks to restructure dynamically and self-heal after mechanical disruption. Phenylboronate-salicylhydroxamate gels provide a new class of self-assembled materials enabling precise control over network viscoelasticity and pH responsiveness. Water-soluble polymers containing 10 mol % phenylboronic acid (PBA) or 10 mol % salicylhydroxamic acid (SHA) were synthesized by free-radical polymerization of functionalized monomers with 2-hydroxypropylmethacrylamide (HPMA) or acrylic acid (AA; Fig. 1b). When aqueous solutions of PBA and SHA containing polymers are mixed at physiological pH, the PBA and SHA moieties associate to form coordinate covalent bonds [25][26][27] (PBA-SHA; Fig. 1a). c Figure 1. Self-healing, viscoelastic hydrogel networks are formed using reversible covalent crosslinking chemistry. a) Covalent bonds that form between polymer-bound phenylboronic acid (PBA) and salicylhydroxamic acid (SHA) have pH-dependent binding equilibria that are shifted to the uncrosslinked state under acidic conditions. b) Linear water-soluble polymers containing either PBA or SHA moieties can be easily synthesized with different polymer backbones (e.g., 2-hydroxypropylmethacrylamide (HPMA) or acrylic acid (AA)) of controlled molar feed ratios. Two degrees of substitution for each polymer were made with x = 90 mol % or 95 mol % (see Supporting Information Table S1 for details). c) When PBA-and SHA-containing polymer solutions are mixed under physiological conditions, a reversible semisolid gel forms due to the dynamic restructuring of the crosslinked gel network. The specific pH range at which gels behave reversibly can be controlled with choice of polymer backbone (in b); HPMA-based PBA-SHA crosslinked gels are reversible at mildly acidic pH (pH 4-5) whi...

pH-induced metal-ligand cross-links inspired by mussel yield self-healing polymer networks with near-covalent elastic moduli

“…By following this strategy the mechanical properties of catechol-Fe 3þ polymer networks can be easily controlled because the networks behave according to the average lifetime of their catechol-Fe 3þ cross-links set by final pH (20). The pH-induced shifts of the frequency of maximum viscous dissipation (f max ) observed in shear rheometry demonstrates this effect (21).…”

Dual Stimuli-Responsive Supramolecular Hydrogel Based on Hybrid Inclusion Complex (HIC)

“…3 Such hydrogels as "smart" soft materials have been found promising in bioapplications 4,5 because they could sense environmental changes and self-induce structural transformations. [6][7][8][9][10][11][12] In the past couple of years, introducing reversible noncovalent bonds as crosslinkers made significant contributions to the research of environmental responsive behavior of hydrogels, especially for redox 13 and pH changes. 14 Obviously, more stimuli responses would generate more flexibility to further applications of the hydrogels.…”

Development of DNA Based Active Macro–Materials for Biology and Medicine: A Review

“…DNA motifs sensitive to changes in H+ concentration has been incorporated in the DNA based hydrogel to realize pH responsiveness. A DNA hydrogel in which gel-'drug' interactions are pH dependent was also proposed (Figure 6B) along with others gels (Roberts et al 2007) ( Table 2). In this design, the electrostatic interactions that retain drugs in the gel network can be reduced resulting in subsequent drug release ).…”

“…The ease with which the mechanical properties of DNA crosslinked gels can be changed suggests that they would be useful in tissue engineering applications. This has generated interests in using DNA as crosslinking agent for various applications , Liedl et al 2007, Murakami & Maeda 2005, Roberts et al 2007, Wei et al 2008, Yang et al 2008). In addition, DNA has also been reported to crosslink organic network such as cellulose (Mangalam et al 2009).…”