Development of a chitosan-hydroxypropyl methylcellulose/nano-fluorapatite hydrogel as a novel biomaterial for enhanced post-tooth extraction bone healing in diabetic conditions

Abstract

A nanocomposite injectable hydrogel based on chitosan (CS), hydroxypropyl methylcellulose (HPMC), and fluorapatite nanoparticles (Nano-FA) was developed and evaluated for its bone regenerative potential following tooth extraction in diabetic rat models. Nano-FA was synthesized via a co-precipitation method and incorporated into a CS–HPMC hydrogel matrix to obtain a homogeneous CS–Nano-FA–HPMC composite. Forty adult male albino rats underwent bilateral extraction of the lower first molars and were randomly divided into four groups: untreated control, CS, Nano-FA, and CS–Nano-FA–HPMC. Bone healing was assessed after 2 and 6 weeks using histological, immunohistochemical, ultrastructural, histomorphometric, biochemical, and energy-dispersive X-ray analyses. The CS–Nano-FA–HPMC group exhibited significantly enhanced bone regeneration compared with the other groups, as evidenced by increased new bone formation, a higher number of entrapped osteocytes, and well-defined bone remodeling lines. Histomorphometric and statistical analyses confirmed that this group achieved the highest percentage of new bone area at both time points. In addition, inflammatory markers were markedly reduced, while osteogenic markers, including alkaline phosphatase and osteocalcin, were significantly elevated in the nanocomposite-treated group. These findings demonstrate that although CS and Nano-FA individually exhibit osteoconductive properties, their combination within a CS–Nano-FA–HPMC hydrogel provides superior regenerative performance, offering a promising strategy for enhancing bone healing under compromised diabetic conditions.