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. 2015;2015:253858.
doi: 10.1155/2015/253858. Epub 2015 Oct 5.

Effects of P-15 Peptide Coated Hydroxyapatite on Tibial Defect Repair In Vivo in Normal and Osteoporotic Rats

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Free PMC article

Effects of P-15 Peptide Coated Hydroxyapatite on Tibial Defect Repair In Vivo in Normal and Osteoporotic Rats

Rasmus Hestehave Pedersen et al. Biomed Res Int. .
Free PMC article

Abstract

This study assessed the efficacy of anorganic bone mineral coated with P-15 peptide (ABM/P-15) on tibia defect repair longitudinally in both normal and osteoporotic rats in vivo. A paired design was used. 24 Norwegian brown rats were divided into normal and osteoporotic groups. 48 cylindrical defects were created in proximal tibias bilaterally. Defects were filled with ABM/P-15 or left empty. Osteoporotic status was assessed by microarchitectural analysis. Microarchitectural properties of proximal tibial defects were evaluated at 4 time points. 21 days after surgery, tibias were harvested for histology and histomorphometry. Significantly increased bone volume fraction, surface density, and connectivity were seen in all groups at days 14 and 21 compared with day 0. Moreover, the structure type of ABM/P-15 group was changed toward typical plate-like structure. Microarchitectural properties of ABM/P-15 treated newly formed bones at 21 days were similar in normal and osteoporotic rats. Histologically, significant bone formation was seen in all groups. Interestingly, significantly increased bone formation was seen in osteoporotic rats treated with ABM/P-15 indicating optimized healing potential. Empty defects showed lower healing potential in osteoporotic bone. In conclusion, ABM/P-15 accelerated bone regeneration in osteoporotic rats but did not enhance bone regeneration in normal rats.

Figures

Figure 1
Figure 1
Study design. Schematic flowchart drawing illustrates the study design and the preparation of the bone samples. After in vivo μCT scanning at four time points, 42 tibias were harvested from 21 rats. The proximal ends of each tibia containing the defect site were decalcified and embedded in paraffin for histomorphometric analyses.
Figure 2
Figure 2
Microarchitectural changes during the induction of osteoporosis. Graphic presentation of the development of osteoporosis in ovariectomized rats. 12 rats were ovariectomized three months prior to the surgery for creating defect. Bone loss was expressed as mean for each parameter. Significantly deteriorated microarchitecture could be observed after 11 weeks, with reduction in bone volume fraction (BV/TV) 65.5% and connectivity density (CD) 77.5%, and more importantly these changes remained constant. Cortical thickness (CoTh), trabecular thickness (TrTh), and degree of anisotropy (DA).
Figure 3
Figure 3
Microarchitectural changes after surgery for creating defect in the normal and the osteoporotic rats. Microarchitectural parameters of the tibial defect areas in normal and osteoporotic rats are presented. Square points represent values from empty groups. Round points represent ABM/P-15 groups. Values are expressed as mean ± SD for groups and are depicted in normal group (a, c, e, g) and in osteoporotic group (b, d, f, h).
Figure 4
Figure 4
Histological images of defect repairs for both normal and osteoporotic rats. Histology images of defects in normal bone (a, c, e) and osteoporotic bone (b, d, f) are shown. Black arrows indicate residual ABM/P-15 particles inside the defect areas. Size lines in bottom right corner represent 1 mm (a–d) and 250 μm (e and f).
Figure 5
Figure 5
Results from histomorphometrical analysis of defect repairs for both normal and osteoporotic rats. Results of histomorphometric analysis for normal and osteoporotic rats 21 days after surgery are presented. Each dot represents mean value of three measurements 500 μm apart in one defect. Horizontal lines express mean for group.

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