Atividade de um hidrogel como sistema de liberação do triterpeno semissintético cl-p2a na regeneração óssea alveolar em ratos wistar

Abstract

Bone loss in the oral region resulting from trauma, infections, or surgical resections poses significant clinical challenges and negatively impacts quality of life. Despite the extensive research on bone tissue regeneration technologies, the clinical application of these approaches still faces important limitations. Combretum leprosum, a shrub endemic to the state of Ceará, Brazil, contains bioactive compounds of pharmacological interest, including the semisynthetic derivative 6β-hydroxy-3β,16β-dipropionyloxylup-20(29)-ene (CL-P2A), which has previously been reported to exhibit osteogenic activity. Therefore, this study investigated the effect of a CL-P2A-loaded hydrogel on alveolar bone regeneration in a tooth extraction model using Wistar rats. A total of 24 animals were allocated into four experimental groups: G1-0% (control), G2-0.5%, G3-1%, and G4-5% CL-P2A. Following bilateral extraction of the maxillary first molars, the hydrogel was applied intra-alveolarly, and the animals were monitored for 21 days. Clinical, histopathological, biochemical, histochemical, and immunohistochemical analyses were performed. Systemic evaluation demonstrated the absence of treatment-related toxicity, with no behavioral changes, impairment of body weight gain, or significant alterations in hepatic and renal histological parameters or serum alanine aminotransferase (ALT) levels. Histopathological analysis of alveolar healing revealed reduced inflammatory infiltrate and increased bone neoformation in the treated groups, with the best performance observed in the G4-5% group, which exhibited thick, mature, and well-organized bone trabeculae. Immunohistochemical analysis of tumor necrosis factor-alpha (TNF-α) demonstrated a dose-dependent reduction in inflammatory expression, with significant suppression of immunostaining in the 5% group. Picrosirius Red staining revealed a progressive increase in collagen fiber deposition and organization, particularly type I collagen, as well as enhanced expression of type II and type III collagens in the G4-5% group, indicating greater extracellular matrix maturation. Serum bone-specific alkaline phosphatase levels also increased proportionally with hydrogel concentration, with the highest values observed in the 5% group. These findings demonstrate that the CL-P2A-loaded hydrogel exhibits a favorable biocompatibility profile, promotes bone regeneration, and exerts dose-dependent anti-inflammatory effects, with the 5% formulation emerging as a promising strategy for alveolar bone regeneration.