Facile Access to Multisensitive and Self-Healing Hydrogels with Reversible and Dynamic Boronic Ester and Disulfide Linkages

Abstract

Multifunctional and multiresponsive hydrogels have presented a promising platform to design and fabricate smart devices for application in a wide variety of fields. However, their preparations often involve multistep preparation of multiresponsive polymer precursors, tedious reactions to introduce functional groups or sophisticated molecular designs. In this work, a multifunctional boronic acid-based cross-linker bis(phenylboronic acid carbamoyl) cystamine (BPBAC) was readily prepared from inexpensive commercially available 3-carboxylphenylboronic acid (CPBA) and cystamine dihydrochloride, which has the ability to cross-link the cis-diols and catechol-containing hydrophilic polymers to form hydrogels. Due to the presence of the reversible and dynamic boronate ester and disulfide bonds, the obtained hydrogels were demonstrated to not only possess pH, glucose, and redox triresponsive features, but also have autonomic self-healing properties under ambient conditions. Moreover, we can modulate the rheological and mechanical properties by simply adjusting the BPBAC amount. The features, such as commercially available starting materials, easy-to-implement approach, and versatility in controlling cross-linking network and mechanical properties, make the strategy described here a promising platform for fabricating multifunctional and smart hydrogels.

Cross‐linking induced thermoresponsive hydrogel with light emitting and self‐healing property

“…Self‐healing hydrogels drew great attentions in past decade because of their self‐healing property similar to the living creatures and wide application in bioscience and biotechnologies . As a result, large amount of self‐healing hydrogels were reported based on both intermolecular force and reversible dynamic bond . The self‐healing hydrogel can be based on a series of dynamic covalent bonds and each has its own advantages.…”

pH and reduction dual‐stimuli‐responsive PEGDA/PAMAM injectable network hydrogels via aza‐michael addition for anticancer drug delivery

“…These stimuli‐responsive polymers and hydrogels have wide applications in drug delivery, emulsification, identification, detection, sensing, coatings, and so forth . The response of such smart polymers (block, graft, star, cyclic, and cross‐linked/hyperbranched polymers) and hydrogels to stimuli such as pH, temperature, redox, light (ultraviolet or visible), and magnetic field has been widely and extensively studied in last decades . Stimuli‐responsive amphiphilic polymers tend to self‐assemble in different morphologies in the aqueous solution and can noncovalently encapsulate hydrophobic dyes and drugs in their self‐assembled structures .…”

“…Stimuli‐responsive functional groups on these polymers can be introduced by modification reactions such as EDC, DCC, and other click/coupling reactions . On the other hand, aliphatic synthetic polymers with stimuli‐responsive groups and the hydrogels therefrom have been widely explored …”

“…Injectable hydrogels with single stimuli‐sensitive group such as acetal, hydrazone, oxime, disulfide, and so forth either in the hydrogel backbone or in the cross‐linker have been synthesized in past decades for targeted anticancer drug delivery and other biological applications . Hydrogel systems which respond to the combination of two or multiple stimuli would be more attractive for targeted or selective and fast/burst release of the encapsulated payloads than the single stimulus‐responsive hydrogels . Therefore, a pH and temperature dual‐responsive injectable hydrogel with a self‐healing ability was prepared by Yu et al by simply mixing the aldehyde modified F127 (PEO‐PPO‐PEO) and acylhydrazine in water to be used only under mildly acidic conditions .…”

Liposomes‐Camouflaged Redox‐Responsive Nanogels to Resolve the Dilemma between Extracellular Stability and Intracellular Drug Release

“…The cross‐linking of nanoparticulate systems by tumor cell microenvironment responsive bonds, such as disulfide, acetal, or hydrazone bonds, has been proven to be an effective route to improve the stability and enable intracellular‐triggered drug release . Especially, the redox‐responsive disulfide bonds had demonstrated great potential for drug delivery in cancer treatment, as the disulfide bonds can remain stable in a predominantly oxidizing extracellular space, while being cleaved by the tumoral intracellular glutathione (GSH, 2–10 × 10 −3 m ) . However, the function of intracellular‐triggered drug release has barely been integrated into the liposomal systems.…”