Modified and Alternative Bone Cements Can Improve the Induced Membrane: Critical Size Bone Defect Model in Rat Femur

Background As a two-stage surgical procedure, Masquelet's technique has been used in the care of critical-size bone defects (CSD). We aimed to determine the effects of modified and altered bone cement with biological or chemical enriching agents on the progression of Masquelet's induced membrane (IM) applied to a rat femur CSD model, and to compare the histopathological, biochemical, and immunohistochemical findings of these cements to enhance IM capacity. Methods Thirty-five male rats were recruited into five groups PMMA, E+PMMA, BC+PMMA, HA, and CPC. The levels of bone alkaline phosphatase (BALP), osteocalcin (OC), and tumor necrosis factor-alpha (TNF-α) were analyzed in intracardiac blood samples collected at the end of 4 weeks of the right femur CSD intervention. All IMs collected were fixed and prepared for histopathological scoring. The tissue levels of rat-specific Transforming Growth Factor-Beta (TGF-β), Runt-related Transcription Factor 2 (Runx2), and Vascular Endothelial Growth Factor (VEGF) were analyzed immunohistochemically. Results Serum levels of BALP and OC were significantly higher in E+PMMA and BC+PMMA groups than those of other groups (P=0.0061 and 0.0019, respectively). In contrast, TNF-α levels of all groups with alternative bone cement significantly decreased compared to bare PMMA (P=0.0116). Histopathological scores of E+PMMA, BC+PMMA, and CPC groups were 6.86±1.57, 4.71±0.76, and 6.57±1.51, respectively, which were considerably higher than those of PMMA and HA groups (3.14±0.70 and 1.86±0.69, respectively) (P<0.0001). Significant increases in TGF-β and VEGF expressions were observed in E+PMMA and CPC groups (P=0.0001 and <0.0001, respectively) whereas Runx2 expression significantly increased only in the HA group compared to other groups (P<0.0001). Conclusions The modified PMMA with E and BC, and CPC as an alternative spacer resulted in a well-differentiated IM and increased IM progression by elevating BALP and OC levels in serum and by mediating expressions of TGF-β and VEGF at the tissue level. The estrogen resulted in relatively promising findings among altered and alternative bone cement.