A self-healing, magnetic and injectable biopolymer hydrogel generated by dual cross-linking for drug delivery and bone repair.

ABSTRACT

Injectable hydrogels based on various functional biocompatible materials have made rapid progress in the field of bone repair. In this study, a self-healing and injectable polysaccharide-based hydrogel was prepared for bone tissue engineering. The hydrogel was made of carboxymethyl chitosan (CMCS) and calcium pre-cross-linked oxidized gellan gum (OGG) cross-linked by the Schiff-base reaction. Meanwhile, magnetic hydroxyapatite/gelatin microspheres (MHGMs) were prepared by the emulsion cross-linking method. The antibacterial drugs, tetracycline hydrochloride (TH) and silver sulfadiazine (AgSD), were embedded into the MHGMs. To improve the mechanical and biological properties of the hydrogels, composite hydrogels were prepared by compounding hydroxyapatite (HAp) and drug-embedded MHGMs. The physical, chemical, mechanical and rheological properties of the composite hydrogels were characterized, as well as in vitro antibacterial tests and biocompatibility assays, respectively. Our results showed that the composite hydrogel with 6% (w/v) HAp and 10 mg/mL MHGMs exhibited good magnetic responsiveness, self-healing and injectability. Compared with the pure hydrogel, the composite hydrogel showed a 38.8% reduction in gelation time (196 to 120 s), a 65.6% decrease in swelling rate (39.4 to 13.6), a 51.9% increase in mass residual after degradation (79.5 to 120.8%), and a 143.7% increase in maximum compressive stress (53.6 to 130.6 KPa). In addition, this composite hydrogel showed good drug retardation properties and antibacterial effects against both S. aureus and E. coli. CCK-8 assay showed that composite hydrogel maintained high cell viability (> 87%) and rapid cell proliferation after 3 days, indicating that this smart hydrogel is expected to be an alternative scaffold for drug delivery and bone regeneration. STATEMENT OF SIGNIFICANCE: Biopolymer hydrogels have been considered as the promising materials for the treatment of tissue engineering and drug delivery. Injectable hydrogels with and self-healing properties and responsiveness to external stimuli have been extensively investigated as cell scaffolds and bone defects, due to their diversity and prolonged lifetime. Magnetism has also been involved in biomedical applications and played significant roles in targeted drug delivery and anti-cancer therapy. We speculate that development of dual cross-linked hydrogels basing biopolymers with multi-functionalities, such as injectable, self-healing, magnetic and anti-bacterial properties, would greatly broaden the application for bone tissue regeneration and drug delivery.