Injectable Self‐Healing Glucose‐Responsive Hydrogels with pH‐Regulated Mechanical Properties

Hydrogels are an appealing class of materials for many biomedical applications, ranging from tissue engineering to drug delivery, and offer a number of functional benefits as a result of their high water content and solid-like mechanical properties. [1–3] Typically, hydrogels are prepared from either covalent or physical cross-linking of hydrophilic polymers to form an insoluble network. Covalently cross-linked hydrogels are typically mechanically stable and elastic, but lack shear-thinning and self-healing properties that are required for applications necessitating minimally invasive injection or catheter delivery. Hydrogels physically cross-linked through ionic interactions, in general, exhibit reduced mechanical properties and are less stable than those produced through covalent cross-linking. Imparting hydrogels with mechanical properties that can be responsive to biologically relevant environmental stimuli could also be of broad interest for biomedical applications. [4,5] The use of dynamic covalent chemistry offers an attractive route in order to prepare hydrogels that could exhibit shear-thinning and self-healing characteristics. These materials would leverage cross-linking mechanisms that arise from a number of recently reported dynamic covalent chemistries. [6–9] One example would be to form hydrogel materials by using the complexation of boronic acids and cis-1,2 or cis-1,3 diol compounds as cross-links in the material. [10–13] The formation of diol–boronic acid complex occurs at pH greater than or equal to the pKa of the boronic acid, and since most boronic acids used to prepare materials through this cross-linking mechanism have pKa values of ≥8 these materials have limited utility in physiologic conditions. [14,15] The pH sensitivity of this dynamic covalent bond does introduce the ability to form dynamically restructuring hydrogels with mechanical properties that are responsive to changes in pH.