Resumen de Effect of Doxycycline in Gel Form on Bone Regeneration: Histomorphometric and Tomographic Study in Rat Calvaria
Amanda C. Silva, Marina R. Oliveira, Lysandro F. A. Amaral, Sabrina Manhães Ferreira, Idelmo R. Garcia Jr., Ronaldo C. Mariano
Background: This study aims to investigate the effects of the local application of doxycycline in the form of natrosol-based gel on bone regeneration by examining critical defects in rat calvaria.
Methods: Twenty-four rats were randomly divided into three groups with eight animals each, according to the treatment received: BC (untreated, filled with blood clot), NAT (natrosol gel alone), and DOX (10% doxycycline gel). Four animals from each group were euthanized at 4 and 8 weeks postoperatively. In tomographic analysis, mean density in the region of the defect was calculated as a percentage relative to the native bone density. In histomorphometric analysis, the newly formed bone area was calculated as a percentage of the total area. The values obtained underwent analysis of variance and Tukey testing (P <0.05).
Results: The mean percentage of tomographic density in the region of the defect at the end of 8 weeks was higher for DOX (44.37%), and statistical differences in this period were observed between DOX and NAT (33.10%) and DOX and BC (32.43%). Regarding new bone formation, at the end of 8 weeks, DOX (61.11%) also had the highest mean bone formation, and statistical differences were observed between DOX and NAT (34.61%) and DOX and BC (23.11%).
Conclusion: It was observed that 10% doxycycline gel had a good effect on bone regeneration regarding the filling of critical defects in rat calvaria.
The high ability of bone tissue to regenerate is one of the most fascinating mechanisms of the body. However, periodontal diseases, tumors, traumas, dental extractions, developmental anomalies, pathologies, oncologic resections, and physiologic bone mass loss may lead to permanent bone defects, which are not capable of regenerating spontaneously. Bone substitutes—which are made from biocompatible materials, have good biomechanical properties, and are able to restore bone functionality—have been applied to dentistry, with focus on reconstructive surgeries of maxillary bone before placement of dental implants, periodontal regeneration, and alveolar ridge reconstruction in congenital cleft lip and palate.1,2 Currently, as possible solutions, autogenous, allogeneic, alloplastic, and xenogeneic grafts and growth factors are used. Each material has advantages and limitations, because recruitment of cells, modulation of the inflammatory process, and promotion of repair by healing or regeneration are influenced by physical, chemical, and biologic characteristics.3 Thus, new biomaterials are sought that can modulate, change, or stimulate osteogenic activity in tissue defects and inhibit osteoclastogenesis.4,5 Doxycycline, a structural isomer of tetracycline, has been continuously studied, mainly because of its well-known antibacterial, anti-inflammatory, anticollagenase, and immunosuppressive features. Its effects in dentistry are proven, mainly by its local application in the treatment of periodontitis and recently peri-implantitis.6-10 Furthermore, recent studies have shown that doxycycline inhibits osteoclastogenesis, a characteristic that makes it favorable in bone regeneration.7,10,11 The inhibition of osteoclastogenesis is undoubtedly an advantageous feature of tetracyclines, since bone manipulation alone, through various surgical procedures, can trigger the activity of osteoclasts.7,10,12 However, no study has been reported in the literature using doxycycline in the form of a 10% gel as a biomaterial that promotes bone regeneration and is not associated with the treatment of periodontal or peri-implant disease. The authors hypothesized that the use of this gel alone can improve bone regeneration, preventing the onset of bone defects and restoring them.
