Highly self-healable and injectable cellulose hydrogels via rapid hydrazone linkage for drug delivery and 3D cell culture

Abstract

To meet the rising demand of injectable hydrogels with self-healing, robustness and biocompatibility for biomedical engineering, the reversible ketoester-type acylhydrazone linkages was used for the fabrication of novel cellulose-based hydrogel. The ketoester-type acylhydrazone bond exchanged rapidly, endowing the hydrogels with highly efficient self-healing performance without any external stimuli under physiological environment, which was hardly achieved with the widely used arylhydrozone bond. The dynamic hydrogels exhibited tunable mechanical property, pH responsiveness, injectability and biocompatibility, demonstrating immense applications prospect for various biomedicines, such as drug and cell delivery. The pH-responsive controlled release of model drug doxorubicin (DOX) loaded in the hydrogel was demonstrated. In addition, benefitting from the excellent biocompatibility and the reversible ketoester-type acylhydrazone bonds, cells were encapsulated in the hydrogels as 3D carrier. The covalent adaptable network intensified injectability of cell-laden hydrogels and improved the long-lasting viability for cell culture, showing great potential in the biomedical field.

Keywords: 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl, PubChem CID: 2723939); 2-Morpholinoethanesulfonic acid (MES, PubChem CID: 16218417); 3D cell encapsulation; 4-Dimethylaminopydine (DMAP, PubChem CID: 14284); 4-Hydroxybenzaldehyde (HBA, PubChem CID: 126); Adipic acid dihydrazide (ADH, PubChem CID: 66117); Doxorubicin (DOX, PubChem CID: 443939); Drug delivery; Injectable hydrogel; Ketoester-type acylhydrazone bonds; N-hydroxysuccinimide (NHS, PubChem CID: 80170); Poly(vinyl alcohol) (PVA, PubChem CID: 11199); Self-healing; tert-Butyl acetoacetate (t-BAA, PubChem CID: 15538).