Biodegradable, biocompatible, and self-healing, injectable hydrogel based on oxidized Azadirachta indica gum and carboxymethyl chitosan through dynamic imine-linkage for biomedical application

Abstract

At physiological temperature (37 °C), neem gum (NG) containing multialdehyde groups (NG-CHO) and carboxymethyl chitosan (CMCh) were combined to formulate an injectable hydrogel through the utilization of dynamic imine linkages. The investigation comprises determining the ideal oxidizing agent concentration to maximize the amount of aldehydes in neem gum. The best-oxidized neem gum determined the minimum gelation time (3 min). The injectable hydrogel's syringeability (~ 99%), porosity (47–71%), self-healing ability, and gel content (58–76%) were evaluated. Characterization techniques, including FTIR and ¹H NMR, confirmed the synthesis, and FESEM showed the morphology of the injectable hydrogel (pore size ~ 80 to 120 µm). Rheometry technique was used for quantitative analysis of shear-thinning behavior and self-healing ability. The swelling ratio was assessed for dry and gel forms of injectable hydrogels in phosphate buffer saline (PBS) at pH 5.5, 7.4, and 8.5. The swelling ratio decreased as the pH increased (5.5–7.4) and then increased at pH 8.5 for all synthesized injectable hydrogels (IHs) in dry and gel forms. For the release assay, an antibiotic model drug, ciprofloxacin HCl (Cipro), was loaded in situ, and the drug release behavior of dry and gel forms of injectable hydrogel was compared within all pH ranges. The drug release kinetics were estimated using the Korsmeyer–Peppas model. Cytotoxicity evaluation using L-929 fibroblast cell lines, antibacterial assay, and hydrolytic degradability (20–65%) in phosphate buffer saline at pH 7.4 was also conducted.

Graphical Abstract