gms | German Medical Science

Objectives: Impaired fracture healing with subsequent implant failure is a dramatic problem in osteoporotic fractures. Metal scaffolds with enhanced mechanical properties are of interest to stimulate fracture healing in osteoporotic defects and the objective of the current study is to investigate the effects of strontium (FeSr) and bisphosphonates (FeBiP) coated iron scaffolds in a critical-size metaphyseal fracture defect of osteoporotic rats compared to plain iron foam (control) and empty defect group.

Methods: 60 female Sprague-Dawley rats were randomized into 4 groups: FeSr, FeBiP, Fe and empty defect (n=15/group). A combinatorial approach of multi-deficiency diet for 3 months after bilateral ovariectomy was used for induction of osteoporosis. Left femur of all animals underwent a 4mm wedge-shaped metaphyseal osteotomy that was internally fixed with a T-shaped plate. The defect was then filled with the mentioned substitutes or left. After 6 weeks femora were harvested followed by histological, histomorphometrical, immunohistochemical , and molecular biology analysis. Time of flight secondary ion mass spectrometry (TOF-SIMS) technology was used to assess the distribution of released strontium and bisphosphonate ions and calcium appearance of newly formed bone. p<0.05 was considered significant.

Results and Conclusion: Histomorphometric analysis showed a statistically significant increase in the bone volume/tissue volume (BV/TV) in the FeSr (p=0.001) and FeBiP (p=0.001) when compared to empty defect. Also a statistically significant increase was seen in both when compared to the plain iron foam (FeSr:p=0.028; FeBiP:p=0.024). An increase in the unmineralized tissue was also seen in all the 3 groups when compared to empty defect (p=0.000). These data were confirmed by the immunohistochemistry results which revealed an increase in bone-morphogenic protein 2, osteocalcin and osteoprotegerin with simultaneous downregulation of RANKL levels. Although no significant differences in blood vessel number were observed in between the groups, an increase in size was seen in the empty defect group. Gene expression analysis also showed a significant decrease in Car2 levels in FeSr (p=0.025) and FeBiP (p=0.048) when compared to empty defect group. TOF-SIMs analysis also showed more mineralized areas in FeSr and FeBiP in the foam region.

Open cell iron foam scaffolds coated with strontium and bisphosphonates enhance bone formation and increase the biocompatibility. These coatings enhance prominent bone formation markers which in turn accentuate bone healing and the porous foams allow adequate blood vessel formation. Therefore, Sr and BiP seem to be a good candidate not only for systemic treatment in osteoporosis but also in Sr and BiP modified biomaterials for local stimulation of new bone formation in osteoporotic fracture defects. This in combination with the known mechanical properties of iron serves as a promising bone graft substitute.