Synthetic hydroxyapatite, silk fibroin and hyaluronic acid in bone regeneration in an experimental model

摘要

Synthetic hydroxyapatite (sHAp) is employed in bone regeneration, given its similarity to mineral phase of bone extracellular matrix and its osteoconductive and osseointregration features. Association of sHAp to polymers is used to obtain composites with improved therapeutic properties. Silk fibroin (SF) has attracted great interest in this field due to its biocompatibility and biodegradability, in addition to provide mechanical strength to the composite. Other components may also be added to the composite in order to improve its properties. In our work, we used hyaluronic acid (HA), a glycosaminoglycan present in extracellular matrix of many tissues, where it participates in tissue formation and repair as well as in the modulation of many cellular processes. This study aimed to evaluate a composite formed by sHAp and FS, combined with 1 % or 3% HA in the regeneration of bone defects in rabbits' olecranon. The project was previously approved by the Ethics Committee on Animal Use, #61/14. Forty animals were distributed into four groups. All animals underwent a surgical procedure to produce a circular 5-mm cortical bone defect on the lateral side of the right olecranon. One group received no treatment (control group) and the other groups had the defect filled with 1) sHAp+FS; 2) sHAp+FS+1 %HA; or 3) sHAp+FS+3%HA. Prior to application, 0.2 g of the material, which was produced as powder, was moistened with sterile saline. Radiographic, tomographic and histological analyses were performed at 7 and 30 days after application. Samples collected at 30th day were also analyzed by scanning electron microscopy. Radiographic evaluation compared gray levels of the defect in relation to the adjacent bone. Analysis of variance only demonstrated the presence of the biomaterial. There was no difference between the moments of observation in radiographic evaluation. Images obtained by tomography showed greater irregularity of the defect edges in the treated group with sHAp+FS+3%HA, suggesting bone formation in those areas. Microscopic analysis showed bone tissue in contact to the biomaterials. Histomorphometric quantification of bone tissue in the defect showed that, between 7 and 30 days, there was a decrease in sHAp+FS group (33.56% to 16.3%), an increased in sHAp+FS+3%HA (26.3% to 43.2%), and no change in the other groups. Although the use of FS and HA in the construction of scaffolds for bone regeneration has been previously demonstrated, in this work, the first may have impaired bone formation. Nevertheless, the formulation and presentation of the materials used in this work are quite different from other reports and so, physical and chemical properties of the combined biomaterials in a composite can significantly change treatment response. According to the result, silk fibroin, as used in this study, presented a negative effect; however, addition of HA improved the biomaterial performance in vivo, resulting in increased bone tissue formation.