Dynamic crosslinked and injectable biohydrogels as extracellular matrix mimics for the delivery of antibiotics and 3D cell culture

Abstract

Antibiotics are widely used in clinical medicine. As an important member, vancomycin often plays an irreplaceable role in some serious infections but for its use, there is still a lack of suitable carriers and effective formulations. To find a vancomycin carrier with potential for clinical applications, a new class of poly(γ-glutamic acid)/dextran-based injectable hydrogels have been constructed through dynamic covalent hydrazone linkages. Adipic dihydrazide (ADH)-grafted poly(γ-glutamic acid) (PGAADH) and sodium periodate-oxidized dextran (OD) precursors were synthesized; then, the hydrogels were formed by blending PGAADH and OD buffer solutions without any additives under physiological conditions. The newly formed precursor structures, mechanical properties, morphologies, hydrogel degradation profiles, and the interaction between the drug and precursors were investigated with FTIR spectroscopy, ¹H NMR spectroscopy, rheological experiments, compression tests, SEM, and isothermal titration calorimetric (ITC) measurements. The resulting hydrogels exhibited excellent antibacterial ability and ideal variable performances. Moreover, the hydrogels exhibited different drug release kinetics and mechanisms and were applied effectively towards the controlled release of vancomycin. Significantly, benefitting from the reversibly cross-linked systems and the excellent biocompatibility, the hydrogels can work as the ideal material for HeLa cell culture, leading to encapsulated cells with higher viability and capacity that is proliferative. Therefore, the injectable PGAADH/OD hydrogels demonstrated attractive properties for future applications in pharmaceutics and tissue engineering.