Desenvolvimento de um Scaffold Biompresso com Pentoxifilina e Tocoferol e avaliação do seu efeito no reparo ósseo alveolar em ratos

Abstract

Bioprinted scaffolds are biomaterials with an adjustable three-dimensional structure that support tissue regeneration and can also function as controlled drug delivery systems. Pentoxifylline (PTX) and tocopherol (TCF) are drugs whose combination has shown promising results in bone regeneration when administered systemically. However, to date, there are no reports in the literature regarding their local action or their formulation associated with biomaterials. The aim of the present study was to develop a bioprinted scaffold containing PTX and TCF and to evaluate its effect in a rat model of alveolar bone repair. The scaffolds were produced by robocasting using a 3D printer (bioplotter®) and characterized by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). FTIR analysis revealed good compatibility among the scaffold components, with characteristic bands and slight shifts. In DSC, the addition of the drugs increased the enthalpy and biodegradability of the polymers. SEM showed surface heterogeneity and alterations in fiber structure associated with drug adsorption. In the experimental protocol, 40 Wistar rats (males and females) were divided into five groups (n=8): BO (positive control; Bio-Oss), PEG/PCL (negative control; polyethylene glycol and polycaprolactone), FC (calcium phosphate), PT (PTX + TCF), and FCPT (FC + PTX + TCF). After extraction of the upper left first molar, the socket was filled with the biomaterial corresponding to each group. Euthanasia was performed at 3 and 6 weeks, and the left hemimaxilla were collected for histopathological and histomorphometric analyses. A micro-computed tomography (micro-CT) analysis was performed on the animals from the 3 week time point. In the histopathological analysis after 3 weeks, the BO group showed better qualitative indicators of bone repair, while the other groups were similar to each other. At 6 weeks, the PT and FCPT groups demonstrated greater tissue organization, reduced inflammatory response, and improved bone maturation parameters compared to the other groups. Histomorphometric analysis revealed that, at 3 weeks, there was an increase in viable osteocytes in the BO, FC, PT, and FCPT groups compared to PEG/PCL; after 6 weeks, only the FCPT group maintained this increase. Osteoblast counts were higher in the BO, FC, PT, and FCPT groups at 3 weeks, and in the BO and FCPT groups at 6 weeks. The presence of osteoclasts was higher in the PEG/PCL group at 3 weeks, with no differences among groups at 6 weeks. Regarding blood vessel counts, the BO, FC, PT, and FCPT groups outperformed PEG/PCL at 3 weeks, and this difference was maintained at 6 weeks only in the BO, PT, and FCPT groups. Finally, micro-CT analysis showed higher bone density and trabecular organization in the groups treated with calcium phosphate and/or the drugs. In conclusion, the bioprinted scaffold modified by the adsorption of FC and/or PTX and TCF showed promising outcomes in bone morphology parameters after 3 and 6 weeks, although further studies are needed to elucidate its mechanisms of action.