Boronate Ester Hydrogels for Biomedical Applications: Challenges and Opportunities.

Boronate ester (BE) hydrogels are increasingly used for biomedical applications. The dynamic nature of these molecular networks enables bond rearrangement, which is associated with viscoelasticity, injectability, printability, and self-healing, among other properties. BEs are also sensitive to pH, redox reactions, and the presence of sugars, which is useful for the design of stimuli-responsive materials. Together, BE hydrogels are interesting scaffolds for use in drug delivery, 3D cell culture, and biofabrication. However, designing stable BE hydrogels at physiological pH (≈7.4) remains a challenge, which is hindering their development and biomedical application. In this context, advanced chemical insights into BE chemistry are being used to design new molecular solutions for material fabrication. This review article summarizes the state of the art in BE hydrogel design for biomedical applications with a focus on the materials chemistry of this class of materials. First, we discuss updated knowledge in BE chemistry including details on the molecular mechanisms associated with BE formation and breakage. Then, we discuss BE hydrogel formation at physiological pH, with an overview of the main systems reported to date along with new perspectives. A last section covers several prominent biomedical applications of BE hydrogels, including drug delivery, 3D cell culture, and bioprinting, with critical insights on the design relevance, limitations and potential.