Modelo experimental de tratamento de osteomielite aguda com polímero reabsorvível contendo vancomicina e sinvastatina implantadas em tíbias de ratos Wistar

Abstract

Osteomyelitis, an infection leading to inflammation, necrosis, and new bone formation, represents a public health challenge in Brazil with 183,975 hospitalizations recorded between 2009 and 2019. Therapeutic options for its treatment include antibiotic therapy and surgical procedures with the implantation of non-absorbable materials such as polymethylmethacrylate (PMMA). However, research focused on the development of new biomaterials associated with tissue engineering has become promising for the treatment of osteomyelitis. In this project, a membrane of Poly(L-coD,L lactic acid-co-trimethylene carbonate) (PLDLA-co-TMC) with vancomycin (VAN) and simvastatin (SIN) was developed and evaluated to treat osteomyelitis in Wistar rat tibias, aiming to combat infection and promote bone regeneration. For this, the PLDLA-co-TMC polymer was synthesized and electrospun with the drugs VAN and SIN and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetry (TG), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM). For the in vivo assay, PLDLA-co-TMC membranes containing VAN and SIN were implanted in the tibias of Wistar rats after the induction of osteomyelitis. Seven days after induction, the rats underwent another surgery for biomaterial implantation, and after fifteen days, they were sacrificed, and their tibias were collected for subsequent analyses. The Wistar rats were divided into 5 groups: negative control (lesion with osteomyelitis), positive control (lesion with osteomyelitis and PLDLA-co-TMC membrane), PLDLA-co-TMC with VAN, with SIN, and with both drugs. Additionally, microbiological assay, drug release assay, interleukin-6 (IL-6) dosage, and evaluation of the macroscopic and microscopic aspects of the lesion were performed. The synthesis of PLDLA-co-TMC membranes with the drugs followed the protocol established in this project. In the characterization study, FTIR, TG, and DSC analysis evidenced the presence of the drugs in the electrospun PLDLA-co-TMC membrane. In the microbiological assay, membranes without drugs and those with only SIN showed no antibiotic activity, whereas those with VAN or both drugs inhibited bacterial growth. In the drug release assay, rapid release was observed for five days, followed by sustained release for thirty days of both drugs. In vivo evaluations, including IL-6 dosage and macroscopic and microscopic analyses of the lesion, showed that the control groups had higher IL-6 production compared to the other groups. Moreover, infection with extravasation into tissues adjacent to the bone was identified in the control groups, in contrast to the other groups that tried to isolate the infectious process by forming abscesses. These results confirm the viability and efficacy of biomaterials in the treatment of osteomyelitis