Combination of Simvastatin, Calcium Silicate/gypsum, and Gelatin and Bone Regeneration in Rabbit Calvarial Defects

Overview

Journal Sci Rep

Specialty Science

Date 2016 Mar 22

PMID 26996657

Citations 6

Authors

Jing Zhang

Huiming Wang

Jue Shi

Ying Wang

Kaichen Lai

Xianyan Yang

Xiaoyi Chen

Guoli Yang

Affiliations

Soon will be listed here.

Abstract

The present study was performed to determine whether simvastatin improves bone regeneration when combined with calcium silicate/gypsum and gelatin (CS-GEL). The surface morphology was determined using field-emission scanning electron microscopy (FSEM). Degradation in vitro was evaluated by monitoring the weight change of the composites soaked in phosphate buffered saline (PBS). Drug release was evaluated using high-performance liquid chromatography (HPLC). Cytotoxicity testing was performed to assess the biocompatibility of composites. Four 5 mm-diameter bone defects were created in rabbit calvaria. Three sites were filled with CS-GEL, 0.5 mg simvastatin-loaded CS-GEL (SIM-0.5) and 1.0 mg simvastatin-loaded CS-GEL (SIM-1.0), respectively, and the fourth was left empty as the control group. Micro-computed tomography (micro-CT) and histological analysis were carried out at 4 and 12 weeks postoperatively. The composites all exhibited three-dimensional structures and showed the residue with nearly 80% after 4 weeks of immersion. Drug release was explosive on the first day and then the release rate remained stable. The composites did not induce any cytotoxicity. The results in vivo demonstrated that the new bone formation and the expressions of BMP-2, OC and type I collagen were improved in the simvastatin-loaded CS-GEL group. It was concluded that the simvastatin-loaded CS-GEL may improve bone regeneration.

Citing Articles

Antimicrobial Peptide-Loaded Pectolite Nanorods for Enhancing Wound-Healing and Biocidal Activity of Titanium.

Zhang L, Xue Y, Gopalakrishnan S, Li K, Han Y, Rotello V ACS Appl Mater Interfaces. 2021; 13(24):28764-28773.

PMID: 34110763 PMC: 8579494. DOI: 10.1021/acsami.1c04895.

The effect of topical administration of simvastatin on entochondrostosis and intramembranous ossification: An animal experiment.

Dang L, Zhu J, Song C J Orthop Translat. 2021; 28:1-9.

PMID: 33575165 PMC: 7844440. DOI: 10.1016/j.jot.2020.11.009.

Effects of statins on the biological features of mesenchymal stem cells and therapeutic implications.

Mahdavi Gorabi A, Kiaie N, Pirro M, Bianconi V, Jamialahmadi T, Sahebkar A Heart Fail Rev. 2020; 26(5):1259-1272.

PMID: 32008148 DOI: 10.1007/s10741-020-09929-9.

Micro-CT - a digital 3D microstructural voyage into scaffolds: a systematic review of the reported methods and results.

Cengiz I, Oliveira J, Reis R Biomater Res. 2018; 22:26.

PMID: 30275969 PMC: 6158835. DOI: 10.1186/s40824-018-0136-8.

Carbonate Apatite Containing Statin Enhances Bone Formation in Healing Incisal Extraction Sockets in Rats.

Rakhmatia Y, Ayukawa Y, Furuhashi A, Koyano K Materials (Basel). 2018; 11(7).

PMID: 30002343 PMC: 6073205. DOI: 10.3390/ma11071201.

References

Thylin M, McConnell J, Schmid M, Reckling R, Ojha J, Bhattacharyya I . Effects of simvastatin gels on murine calvarial bone. J Periodontol. 2002; 73(10):1141-8. DOI: 10.1902/jop.2002.73.10.1141. View

Anbinder A, Junqueira J, Mancini M, Balducci I, Rocha R, Carvalho Y . Influence of simvastatin on bone regeneration of tibial defects and blood cholesterol level in rats. Braz Dent J. 2007; 17(4):267-73. DOI: 10.1590/s0103-64402006000400001. View

Wang J, Xu S, Yang D, Lv R . Locally applied simvastatin promotes fracture healing in ovariectomized rat. Osteoporos Int. 2007; 18(12):1641-50. DOI: 10.1007/s00198-007-0412-2. View

Burg K, Porter S, Kellam J . Biomaterial developments for bone tissue engineering. Biomaterials. 2000; 21(23):2347-59. DOI: 10.1016/s0142-9612(00)00102-2. View

Coraca-Huber D, Wurm A, Fille M, Hausdorfer J, Nogler M, Vogt S . Antibiotic-loaded calcium carbonate/calcium sulfate granules as co-adjuvant for bone grafting. J Mater Sci Mater Med. 2015; 26(1):5344. DOI: 10.1007/s10856-014-5344-8. View

PELTIER L . The use of plaster of paris to fill large defects in bone. Am J Surg. 1959; 97(3):311-5. DOI: 10.1016/0002-9610(59)90305-8. View

Jacobson R, Wang P, Glueck C . Myositis and rhabdomyolysis associated with concurrent use of simvastatin and nefazodone. JAMA. 1997; 277(4):296-7. DOI: 10.1001/jama.277.4.296. View

Edwards M, Ousterhout D . Autogeneic skull bone grafts to reconstruct large or complex skull defects in children and adolescents. Neurosurgery. 1987; 20(2):273-80. DOI: 10.1227/00006123-198702000-00013. View

Huang X, Huang Z, Li W . Highly efficient release of simvastatin from simvastatin-loaded calcium sulphate scaffolds enhances segmental bone regeneration in rabbits. Mol Med Rep. 2014; 9(6):2152-8. PMC: 4055438. DOI: 10.3892/mmr.2014.2101. View

10.

Fu Y, Wang Y, Chen C, Wang C, Wang G, Ho M . Combination of calcium sulfate and simvastatin-controlled release microspheres enhances bone repair in critical-sized rat calvarial bone defects. Int J Nanomedicine. 2015; 10:7231-40. PMC: 4671780. DOI: 10.2147/IJN.S88134. View

11.

Montagnani A, Gonnelli S, Cepollaro C, Pacini S, Campagna M, Franci M . Effect of simvastatin treatment on bone mineral density and bone turnover in hypercholesterolemic postmenopausal women: a 1-year longitudinal study. Bone. 2003; 32(4):427-33. DOI: 10.1016/s8756-3282(03)00034-6. View

12.

Hu G, Xiao L, Fu H, Bi D, Ma H, Tong P . Study on injectable and degradable cement of calcium sulphate and calcium phosphate for bone repair. J Mater Sci Mater Med. 2009; 21(2):627-34. DOI: 10.1007/s10856-009-3885-z. View

13.

Fuentes I, Aguilera C . [Myopathy secondary to the treatment with inhibitors of HMG-CoA reductase]. Med Clin (Barc). 1999; 111(18):700. View

14.

Liu Q, de Wijn J, van Blitterswijk C . Nano-apatite/polymer composites: mechanical and physicochemical characteristics. Biomaterials. 1997; 18(19):1263-70. DOI: 10.1016/s0142-9612(97)00069-0. View

15.

Nyan M, Sato D, Oda M, Machida T, Kobayashi H, Nakamura T . Bone formation with the combination of simvastatin and calcium sulfate in critical-sized rat calvarial defect. J Pharmacol Sci. 2007; 104(4):384-6. DOI: 10.1254/jphs.sc0070184. View

16.

Zhang H, Xiao G, Wang X, Dong Z, Ma Z, Li L . Biocompatibility and osteogenesis of calcium phosphate composite scaffolds containing simvastatin-loaded PLGA microspheres for bone tissue engineering. J Biomed Mater Res A. 2015; 103(10):3250-8. DOI: 10.1002/jbm.a.35463. View

17.

Papadimitriou K, Karkavelas G, Vouros I, Kessopoulou E, Konstantinidis A . Effects of local application of simvastatin on bone regeneration in femoral bone defects in rabbit. J Craniomaxillofac Surg. 2014; 43(2):232-7. DOI: 10.1016/j.jcms.2014.11.011. View

18.

Du Z, Chen J, Yan F, Xiao Y . Effects of Simvastatin on bone healing around titanium implants in osteoporotic rats. Clin Oral Implants Res. 2008; 20(2):145-50. DOI: 10.1111/j.1600-0501.2008.01630.x. View

19.

Zhou S, Ma J, Shen Y, Haapasalo M, Ruse N, Yang Q . In vitro studies of calcium phosphate silicate bone cements. J Mater Sci Mater Med. 2012; 24(2):355-64. DOI: 10.1007/s10856-012-4794-0. View

20.

Orellana B, Hilt J, Puleo D . Drug release from calcium sulfate-based composites. J Biomed Mater Res B Appl Biomater. 2014; 103(1):135-42. PMC: 4302276. DOI: 10.1002/jbm.b.33181. View