Environment Controls Biomolecule Release from Dynamic Covalent Hydrogels

Moldable hydrogels composed of dynamic covalent bonds are attractive biomaterials for controlled release, as the dynamic exchange of bonds in these networks enables minimally invasive application via injection. Despite the growing interest in the biomedical application of dynamic covalent hydrogels, there is a lack of fundamental understanding as to how the network design and local environment control the release of biomolecules from these materials. In this work, we fabricated boronic-ester-based dynamic covalent hydrogels for the encapsulation and in vitro release of a model biologic (beta-galactosidase). We systematically investigated the role of network properties and of the external environment (temperature and presence of competitive binders) on release from these dynamic covalent hydrogels. We observed that surface erosion (and associated mass loss) governed biomolecule release. In addition, we developed a statistical model of surface erosion based on the binding equilibria in a boundary layer that described the rates of release. In total, our results will guide the design of dynamic covalent hydrogels as biomaterials for drug delivery applications.

Automated summary

In this study, boronic-ester-based dynamic covalent hydrogels were developed for encapsulating and releasing a model biologic. The research systematically investigated the impact of network properties and external environment on the release process, with surface erosion identified as the governing mechanism for biomolecule release. Additionally, a statistical model based on binding equilibria in the boundary layer was developed to describe the release rates. Overall, these results provide valuable insights for designing dynamic covalent hydrogels for drug delivery applications.