Mandibular bone defect healing using polylactic acid–nano-hydroxyapatite–gelatin scaffold loaded with hesperidin and dental pulp stem cells in rat

Abstract

Addressing mandibular defects poses a significant challenge in maxillofacial surgery. Recent advancements have led to the development of various biomimetic composite scaffolds aimed at facilitating mandibular defect reconstruction. This study aimed to assess the regenerative potential of a novel composite scaffold consisting of polylactic acid (PLA), hydroxyapatite nanoparticles (n-HA), gelatin, hesperidin, and human dental pulp stem cells (DPSCs) in a rat model of mandibular bone defect. The PLA-HA-GLA composite was synthesized using solvent casting-leaching and freeze-drying methods and subsequently treated with 11 mg of hesperidin. The physicochemical properties of the PLA-HA-GLA and PLA-HA-GLA-HIS composites were analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and thermal gravimetric analysis (TGA). Additionally, the mechanical properties and cytotoxicity of DPSCs were assessed. Subsequently, PLA-HA-GLA and PLA-HA-GLA-HIS scaffolds with or without DPSCs were implanted into mandibular bone defects in rats, followed by histopathological, histomorphometric, and cone-beam computed tomography (CBCT) evaluations after eight weeks. SEM analysis revealed the porous structure of the fabricated PLA-HA-GLA and PLA-HA-GLA-HIS composites without aggregation. FTIR and XRD analyses confirmed the presence of functional groups and elements associated with PLA, HA, GLA, and hesperidin in the composites. Although the PLA-HA-GLA-HIS composite exhibited good thermal stability, its mechanical properties decreased after the addition of hesperidin. The cell viability of DPSCs on the surface of the PLA-HA-GLA-HIS scaffolds was statistically significant compared to that of the control group. Furthermore, histopathological, histomorphometric, and radiological evaluations demonstrated that the implantation of the DPSC-loaded PLA-HA-GLA-HIS scaffold had a beneficial effect on bone tissue reconstruction in rats with mandibular defects. These findings highlight the potential of DPSC-loaded PLA-HA-GLA-HIS composite scaffolds for spongy bone tissue engineering and mandibular defect repair.