Topical Simvastatin Improves the Pro-Angiogenic and Pro-Osteogenic Properties of Bioglass Putty in the Rat Calvaria Critical-Size Model
Objective was to describe the effect of bioactive glass putty with and without topical simvastatin on new bone formation in critical-sized defects of rat calvaria. A calvarial bone defect was created in 20 male Wistar rats and filled with bioactive glass alone (n = 10) or combined with simvastatin (n = 10). After 4 weeks, the defects were histomorphometrically evaluated for volume fraction (Vv) of woven bone, vessel density, bioglass quantity, and inflammation. Compared to the bioglass-only group, rats treated with simvastatin had greater Vv of blood vessels (3.3% ± 0.7 vs 1.6% ± 0.1, P = .0002) and new bone (2.3% ± 0.2 vs 1.8% ± 2.5, P = .003). The Vv of the bioglass remnants in the bioglass-only group was higher than in the group treated with simvastatin (2.4% ± 0.08 vs 1.7% ± 0.3, P < .0004). Chronic inflammation was noted in 1 rat from each group. Topical simvastatin seems to improve the pro-angiogenic and pro-osteogenic properties of bioglass putty in rat calvaria critical-size defects without significant inflammation.
Figure 1. Bioglass remnants, represented by hollowed structures (arrows) in the defect area, are present 4 weeks after surgery (hematoxylin and eosin ×100 magnification). Figure 2. Chronic inflammatory infiltrate composed mainly of lymphocytes and plasma cells was present in 2 cases, 1 from each group (hematoxylin and eosin [H&E] ×200 magnification). Figure 3. Newly formed bone in the defect area in which viable osteocytes (thick arrow) are present as well as osteoblastic rimming (H&E ×200 magnification). Figure 4. Bone neoformation in the BGS group: woven bone with abundant osteoblasts (thin arrows) and blood vessels (thick yellow arrow) in close proximity to bioglass hollows (thick black arrow) is noted (H&E magnification). Figure 5. Angiogenesis and osteogenesis. Woven bone with osteoblasts (thick black arrows) and osteoid (thin black arrows) seems to “emerge” in the center of the bioglass hollows (star), growing towards the periphery. Blood vessels are abundant (H&E ×100 magnification). Figure 6. Remaining bioglass hollows (thin arrows) are seen in proximity to new bone (star) (H&E ×100 magnification). Figure 7. Bone formation begins in the center of the hollowed structures (star) and progresses towards the periphery. Osteocytes (thick arrow) and osteoid (thin arrow) are noted (H&E ×400 magnification). Figure 8. Bone neoformation merely occupies the hollowed structures (star). Osteocytes (thick arrow) and osteoid (thin arrow) noted (H&E ×400 magnification). Figure 9. In the BGS group, the center of the hollowed structures contains either osteoid/woven bone, represented by blue staining (thin arrows), or bioglass remnants, in red (thick arrow). More mature bone (left) stains red as well (Masson trichrome ×100 magnification).
Mean volume fraction (%) of woven bone, blood vessels and bioglass remnants in the Bioglass + simvastatin group (red) compared to the Bioglass group (blue).
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