Treatment of critical-sized calvarial non-union defect via collagen-polyglycolic acid scaffold loading with simvastatin in rabbits

Document Type : Research Articles

Authors

• Hooman Mesgarani ¹
• Jebrail Movafagh ²
• Hossein Nourani ¹
• Javad Behravan ³
• Fatemeh Kalalinia ⁴
• Hossein Kazemi Mehrjerdi ¹

¹ Ferdowsi University of Mashhad

² Mashhad University Medical sciences

³ School of Pharmacy

⁴ Mashhad University of Medical Sciences

10.22067/veterinary.v8i2.58623

Abstract

The aim of the present study is to investigate the effects of a sustained-release simvastatin in collagen-polyglycolic acid scaffold on bone formation in the rabbit calvarial critical-sized defect. This study was carried out to examine if maximum bone regeneration with less inflammation would be attained by combining an optimal dose of simvastatin with Collagen-Polyglycolic acid scaffold, which is an osteoconductive biomaterial capable of releasing the drug slowly. To induce critical-sized calvarial defect in the 10 nominated adult New-Zealand rabbits we trephined four holes measured 5-mm-diameter into each head, and filled them with preparations of different doses of simvastatin (0.5 mg, and 1 mg) blended with Collagen-Polyglycolic acid, Scaffold alone or left empty. Five animals were sacrificed after 4 weeks and the rest of them after 8 weeks and examined histologically. Statistical analysis revealed that in the first time frame (the first four weeks), the difference between the control group and the simvastatin 0.5 mg group on one hand and the simvastatin 1 mg group
and the control group on the other hand, there were statistically significant difference between (p < 0.05). In the second time frame (the next four weeks), there were statistically significant differences between the simvastatin 0.5 mg group and the control group, and between the scaffold group and the control group (p

Keywords

• collagen
• polyglycolic acid
• bone formation
• simvastatin
• scaffold

20.1001.1.2008465.2016.8.2.2.2

Main Subjects

• Pharmacology

---

References

An, Y. H., & Martin, K. L. (Eds.). (2003). Handbook of histology methods for bone and cartilage (p. 587). Totowa, NJ: Humana Press.

Aybar, O. A., Territoriale, E., &Missana, L. (2004). An experimental model in calvaria to evaluate bone therapies. Actaodontologica latino americana: AOL, 18(2), 63-67.

Agrawal, C., & Ray, R. B. (2001). Biodegradable polymeric scaffolds for musculoskeletal tissue engineering. Journal of biomedical materials research, 55(2), 141-150.

Chevallay, B., & Herbage, D. (2000). Collagen-based biomaterials as 3D scaffold for cell cultures: applications for tissue engineering and gene therapy. Medical and Biological Engineering and Computing, 38(2), 211-218.

Huang, X., Huang, Z., & Li, W. (2014). Highly efficient release of simvastatin from simvastatin loaded calcium sulphate scaffolds enhances segmental bone regeneration in rabbits. Molecular medicine reports, 9(6), 2152-2158.

Hussain, A., Takahashi, K., Sonobe, J., Tabata, Y., &Bessho, K. (2014). Bone regeneration of rat calvarial defect by magnesium calcium phosphate gelatin scaffolds with or without bone morphogenetic protein-2. Journal of maxillofacial and oral surgery, 13(1), 29-35.

Hiraoka, Y., Kimura, Y., Ueda, H., &Tabata, Y. (2003). Fabrication and biocompatibility of collagen sponge reinforced with poly (glycolic acid) fiber.Tissue engineering, 9(6), 1101-1112.

Karimi, I., Bigham-Sadegh, A., & Oryan, A. (2013). Concurrent Use of Greater Omentum with Persian Gulf Coral on Bone Healing in Dog: a Radiological and Histopathological Study. Iranian Journal of Veterinary Surgery, 8(2), 35-42.

Khadra, M., Kasem, N., Haanæs, H. R., Ellingsen, J. E., & Lyngstadaas, S. P. (2004). Enhancement of bone formation

in rat calvarial bone defects using low-level laser therapy. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 97(6), 693-700.

Mariano, R., Messora, M., de Morais, A., Nagata, M., Furlaneto, F., Avelino, C., ...& de Sene, J. P. (2010). Bone healing in critical-size defects treated with platelet-rich plasma: a histologic and histometric study in the calvaria of diabetic rat. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 109(1), 72-78.

Mukozawa, A., Ueki, K., Marukawa, K., Okabe, K., Moroi, A., & Nakagawa, K. (2011). Bone healing of critical‐sized nasal defects in rabbits by statins in two different carriers. Clinical oral implants research, 22(11), 1327-1335.

Nyan, M., Sato, D., Kihara, H., Machida, T., Ohya, K., & Kasugai, S. (2009). Effects of the combination with αtricalcium phosphate and simvastatin on bone regeneration. Clinical oral implants research, 20(3), 280-287.

O’brien, F. J. (2011). Biomaterials & scaf

folds for tissue engineering. Materials today, 14(3), 88-95.

Özeç, I., Kiliç, E., Gümüs, C., &Göze, F. (2007). Effect of local simvastatin application on mandibular defects. Journal of Craniofacial Surgery, 18(3), 546-550.

Park, J. B. (2009). The use of simvastatin in bone regeneration. Medicina Oral Patologia Oral y Cirugia Bucal, 14(9), e485-e488.

Stein, D., Lee, Y., Schmid, M. J., Killpack, B., Genrich, M. A., Narayana, N., ...& Reinhardt, R. A. (2005). Local simvastatin effects on mandibular bone growth and inflammation. Journal of periodontology, 76(11), 1861-1870.

Thylin, M. R., McConnell, J. C., Schmid, M. J., Reckling, R. R., Ojha, J., Bhattacharyya, I., ... & Reinhardt, R. A. (2002). Effects of simvastatin gels on murine calvarial bone. Journal of periodontology, 73(10), 1141-1148.

Toosi, S., Naderi‐Meshkin, H., Kalalinia, F., Peivandi, M. T., HosseinKhani, H., Bahrami, A. R., & Behravan, J. (2016). PGA‐incorporated collagen: Toward a biodegradable composite

scaffold for bone‐tissue engineering. Journal of Biomedical Materials Research Part A. 104(8), 2020-2028.

Tseng, S. S., Lee, M. A., &Reddi, A. H. (2008). Nonunions and the potential of stem cells in fracture-healing. The Journal of Bone & Joint Surgery, 90 (Supplement 1), 92-98.

Weitz-Schmidt, G. (2002). Statins as anti-inflammatory agents. Trends in pharmacological sciences, 23(10), 482-487.

Yaszemski, M. J., Payne, R. G., Hayes, W. C., Langer, R., &Mikos, A. G. (1996). Evolution of bone transplantation: molecular, cellular and tissue strategies to engineer human bone. Biomaterials, 17(2), 175-185.

Yueyi, C., Xiaoguang, H., Jingying, W., Quansheng, S., Jie, T., Xin, F., ...&Chunli, S. (2013). Calvarial defect healing by recruitment of autogenous osteogenic stem cells using locally applied simvastatin. Biomaterials,34(37), 9373-9380.