Bioinspired Self-Healing of Kinetically Inert Hydrogels Mediated by Chemical Nutrient Supply

Abstract

Dynamic stability and self-healing ability are two inherently compatible properties for living organisms. By contrast, kinetic stability and intrinsic healability are two desired but mostly incompatible properties for synthetic materials. This is because the healing of these materials heavily relies on the kinetic lability of the chemical bonds or physical interactions in materials. Inspired by the hierarchically and temporally controlled wound healing in biological systems, here, we report the intrinsic healing of kinetically stable hydrogels, regulated by the consumption of chemical nutrients. The acylhydrazone-based polymer hydrogels with preinstalled urease and urea were formed at a low initial pH, followed by in situ enzymatic generation of a base to deactivate the dynamic bonds, allowing efficient fabrication of kinetically stable hydrogels. The healing of damaged hydrogels was effective when fed with proper chemical nutrients (i.e., acidic urea solutions), in which case a transient acidic pH state was temporally programmed by combining a fast acidic activator (for structural healing) with the slow, biocatalytic generation of a base (for property recovery). The ability to regulate both hydrogel fabrication and healing via a single enzymatic reaction could provide a new approach to create kinetically stable materials capable of healing damages on demand.

Programming properties of transient hydrogels by an enzymatic reaction

“…S4, † than compound 3. 51 Because of this, gelation occurs rapidly at low pH as compared to that at high pH. These observations are quite similar to the polymer system reported by Wang group, where the formation of acylhydrazone bonds was efficient at a low initial pH of 4 and further activation of the acylhydrazone bonds through protonation not only led to rapid hydrogelation but also allowed good healing capability under acidic condition.…”

“…These observations are quite similar to the polymer system reported by Wang group, where the formation of acylhydrazone bonds was efficient at a low initial pH of 4 and further activation of the acylhydrazone bonds through protonation not only led to rapid hydrogelation but also allowed good healing capability under acidic condition. 51 However, when the pH is sufficiently low, all the molecules of 3 become protonated and we assume destroy the hydrogen bonded network through electrostatic repulsion. The increased polarity of the compound then aids the dissolution of the gel.…”

“…S4 †), leading to an orange coloured transient hydrogel. 51 In presence of base, no such seeding-induced self-assembly occurs. Rather, the system spontaneously drives to a thermodynamically stable yet kinetically trapped yellow coloured hydrogel over time.…”

Enzyme-Regulated Healable Polymeric Hydrogels

“…Reprinted with permissions. 5 , 15 , 32 , 60 , 63 , 70 , 73 Copyright Wiley-VCH, American Chemical Society, and Royal Society of Chemistry.…”

“… 32 , 60 − 62 The initial use of enzymatic reactions in polymeric hydrogels is for material construction, 63 − 65 and then followed by enzymatic fabrication of healable polymeric hydrogels 60 , 66 − 70 and enzymatically regulated healing of polymeric hydrogels. 32 , 71 , 72 The latest progress of this field is to use the enzymatic reaction to mediate the transient healing ability of polymeric hydrogels, 73 , 74 which not only enables the fabrication of thermodynamically stable and kinetically inert hydrogels but also endows such hydrogels with an intrinsic healing ability on demand.…”