Dynamically Crosslinked Hydrogels Composed of Carboxymethyl Chitosan and Tannic Acid for Sustained Release of Encapsulated Protein

Abstract

Polysaccharide-based hydrogels are promising for biomedical applications such as drug delivery owing to their biocompatibility, biodegradability, and bioactivities. In particular, there is a need for hydrogels with injectability for minimally invasive therapies and controlled sustained release for sustained drug effect. Hydrogels made from carboxymethyl chitosan (CMC) and tannic acid (TA) (CMC-TA) contain dynamic covalent bonds owing to autoxidation between CMC and TA, and interact with proteins via TA, elucidation of the detailed mechanism of dynamic covalent bonding in CMC-TA hydrogels will facilitate stable loading and zero-order release of proteins. Herein, the physical properties of oxidized CMC-TA (Oxi-CMC-TA) prepared for the encapsulation and sustained release of proteins are explored. Following incubation at 37 °C for 24 h, CMC-TA undergoes secondary crosslinking by autoxidation to produce Oxi-CMC-TA. Notably, CMC-TA is viscoelastic and shear-thinning, allowing for injection and 3D bioprinting. Indeed, CMC-TA can be 3D-printed with green fluorescent protein (GFP) encapsulated in its matrix. Oxi-CMC-TA also exhibits an affinity for protein owing to its gallol groups, enabling Oxi-CMC-TA to collect GFP in aqueous solutions against a concentration gradient. Moreover, Oxi-CMC-TA releases GFP over 15 days. Injectable, 3D-printable, protein-collecting, and zero-order sustained-releasing Oxi-CMC-TA has the potential to make a significant contribution to drug delivery.