Characterization and therapeutic effects of an atorvastatin graphene oxide hydrogel on medication induced osteonecrosis of the jaws in female rats

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating oral condition. Atorvastatin (ATV) has angiogenic, anti-inflammatory, and bone anabolic properties, but long-term use may lead to systemic side effects. This study aims to develop, characterize, and evaluate a hydrogel based on hydroxypropylmethylcellulose (HPMC) and graphene oxide (GO), loaded with ATV, to mitigate alveolar bone necrosis. The composites obtained were analyzed using FTIR, XRD, TGA, and SEM. ATV adsorption onto GO and rheological tests assessed its suitability for in vivo applications. A preclinical study was conducted in female Wistar rats using a model of MRONJ induced by Zoledronic Acid (ZA). Following tooth extraction, the animals received either 1.2% ATV hydrogel or placebo hydrogel. Euthanasia was performed three weeks post-extraction, and the maxillae, blood samples, liver, and kidney were collected for analyses. Physical-chemical analyses revealed that lyophilized GO adsorbed 85.0% of ATV in solution. SEM images showed a porous hydrogel structure and amorphous ATV within the polymeric matrix, while rheological studies confirmed pseudoplastic behavior. In vivo, the ATV hydrogel mitigated MRONJ lesions, promoted mucosal healing, increased the osteocyte count by 53.0%, and improved bone quality and strength. It also reduced inflammation and enhanced blood vessel formation (+ 65.0%). No systemic alterations were observed.