Modular Design and Bonding Mechanism of Internal Boron–Nitrogen Coordinated Boronic Ester Hydrogels with Alkaline pH Responsiveness and Tunable Gelation pH

Abstract

Boronic ester hydrogels have been widely used in biomedical fields for their stimuli responsiveness to multiple disease-related triggers. However, the restricted pH for gelation and the poor hydrolysis stability limit their application in variable physiological microenvironments. Here, we report a modular conjugation method for designing internal boron−nitrogen coordinated boronic ester (IBNCB) hydrogels by constructing polymers with phenylboronic acid or N,N-bis(2-hydroxyethyl) moieties based on amides. Eight distinct IBNCB hydrogel models composed of polymer/polymer or polymer/micromolecule were prepared, exhibiting a unique pH responsiveness in the alkaline environment, an enhanced hydrolysis stability, bidirectional pHtunable mechanical properties, and a lowered and tunable pH for gelation. In addition, the IBNCB hydrogels maintained a sol−gel transitional responsiveness to reactive oxygen species (ROS), glucose, and temperature. Especially, we found that the pH required to form an ideal IBNCB hydrogel should be greater than the pK a of phenylboronic acid but lower than the pK a of N,N-bis(2hydroxyethyl), and reducing the pK a of phenylboronic acid could lower the gelation pH. The pK a of the tertiary amine in N,N-bis(2hydroxyethyl) was shown to be important in the creation of the B−N coordination bond, which influenced the formation of the IBNCB bond. Finally, we explored the effect of the main chain's charge on gelability and proposed the dynamic equilibrium mechanism of IBNCB bonds in the hydrogel. We expect that the multi-stimuli-responsive IBNCB hydrogels will provide a new strategy for designing smart materials sensitive to physicochemical signals. Furthermore, the amide-based modular conjugation could be exploited to generate a theoretically limitless number of novel IBNCB materials including microgels, polymer vesicles, and micro−nano particles.

Nonconjugated Organic Room-Temperature Phosphorescent Vitrimers with Multicolor Afterglow via Multicomponent Hybrid Copolymerization

“…Additionally, the modulus was as high as 726.63 MPa. Because of the many dynamic covalent bonds, PBEHA could be reprocessed at 120 °C and 10 MPa for 2 min. , The tensile strength and elongation-at-break of the restored splines were 85.2 MPa and 18.3%, respectively, which were similar to those before remolding. Reducing the amount of AM will lead to a significant decrease in the tensile strength (Table S1).…”

Cross‐Linking Strategies for Silk‐Protein‐Based Inks for 3D Printing

“…This suggests that SF is able to accelerate the regeneration of β‐sheets and increase intermolecular interactions by mechanical stirring, ultrasonic oscillation or shear stress, thereby accelerating ink sol‐gel changes [108–110] . In addition, the ways that induce physical cross‐linking include factors such as temperature, pH, thickening agents, surfactants and metal ion reagents [111–118] …”

“…[108][109][110] In addition, the ways that induce physical cross-linking include factors such as temperature, pH, thickening agents, surfactants and metal ion reagents. [111][112][113][114][115][116][117][118] A simple method of physical cross-linking is the addition of thickening agents. Common thickening agents are mainly hydrophilic, intrinsically viscous materials.…”

Regulating Boronic Ester Bonds in Bilayer Hydrogels toward Fabricating Multistimuli-Triggered Actuators

“…This structure is reversible, which depends on the environmental pH and temperature. , Increasing pH or decreasing temperature is conducive to cyclization, and accordingly, this dynamic bonding can be used as a structural design strategy for fabricating the pH- or temperature-triggered substrates to detect biomolecules or to deliver drug components. − The most attractive feature of B–O bonding is that the reactants such as borax are water-soluble, and boronic acid formed via the hydrolysis of borax acts as a Lewis acid to accept electron pairs, forming the complexes with Lewis bases. , In other words, B–O bonding easily occurs in aqueous solutions with water-soluble polyols or other substrates with electron-donating groups. Thus, B–O bonding has been widely used as a networking strategy to fabricate hydrogel materials. − The reported studies around the hydrogels with B–O bonds are mainly involved (a) as a structural unit to construct the secondary (weak) networks or cross-links for improving mechanical performance of hydrogels; , (b) as a responsive unit to endow the networks with reconstruction capability for realizing multistimulus responsiveness; − and (c) as a functional unit to fabricate ionic hydrogels for developing flexible devices. , The as-prepared dynamic hydrogels with B–O bonds show promising applications in the fields of sensors, biomedicine, and tissue engineering. , …”

“…21,22 The as-prepared dynamic hydrogels with B−O bonds show promising applications in the fields of sensors, biomedicine, and tissue engineering. 23,24 It is well known that a soft actuator is also one of the important applications for hydrogels with multiple networks or cross-links. The driving force of achieving the reversible or programmable shape transformation of the hydrogels commonly arises from the mechanical instability caused by asymmetric swelling/deswelling capacities of different parts of the hydrogel bulk.…”