Local injection of lovastatin in biodegradable polyurethane scaffolds enhances bone regeneration in a critical-sized segmental defect in rat femora

Journal of Tissue Engineering and Regenerative Medicine

Volumn 8, Issue 8, 2014, Pages 589-595

  Yoshii, Toshitaka ^a,b   Hafeman, Andrea E ^b,c   Esparza, Javier M ^b,d   Okawa, Atsushi ^a   Gutierrez, Gloria ^b,d   Guelcher, Scott A ^b,c  

^a TOKYO MEDICAL AND DENTAL UNIVERSITY   (Japan)

^b VANDERBILT UNIVERSITY   (United States)

^c VANDERBILT UNIVERSITY   (United States)

^d VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Bone regeneration; Injection; Lovastatin; Microparticles; Polyurethane; Scaffold; Segmental defect

Indexed keywords

BONE; COMPUTERIZED TOMOGRAPHY; CONTROL SYSTEM SYNTHESIS; GENE EXPRESSION; POLYURETHANES; RATS; SCAFFOLDS (BIOLOGY);

BIODEGRADABLE POLYURETHANES; BONE MORPHOGENETIC PROTEIN-2; BONE REGENERATION; INJECTION; LOVASTATIN; MICRO PARTICLES; POLYURETHANE SCAFFOLDS; RAT FEMUR; SEGMENTAL DEFECTS; STATINS;

DEFECTS;

BONE MORPHOGENETIC PROTEIN 2; MEVINOLIN; POLYURETHAN; BIOMATERIAL; MICROSPHERE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOLOGICAL ACTIVITY; BMP 2 GENE; BONE DENSITY; BONE MASS; BONE REGENERATION; CONTROLLED STUDY; DIAPHYSIS; FEMUR FRACTURE; GENE; GENE EXPRESSION; HISTOPATHOLOGY; METAPHYSIS; MICRO-COMPUTED TOMOGRAPHY; NONHUMAN; OSSIFICATION; OSTEOBLAST; PRIORITY JOURNAL; RAT; SUSTAINED DRUG RELEASE; ANIMAL; CELL LINE; CHEMISTRY; DISEASE MODEL; DRUG EFFECTS; FEMUR; INJECTION; KINETICS; MOUSE; PATHOLOGY; RADIOGRAPHY; TISSUE SCAFFOLD;

ANIMALS; BIOCOMPATIBLE MATERIALS; BONE REGENERATION; CELL LINE; DISEASE MODELS, ANIMAL; FEMUR; INJECTIONS; KINETICS; LOVASTATIN; MICE; MICROSPHERES; POLYURETHANES; RATS; TISSUE SCAFFOLDS; X-RAY MICROTOMOGRAPHY;

EID: 84904959567     PISSN: 19326254     EISSN: 19327005     Source Type: Journal    
DOI: 10.1002/term.1547     Document Type: Article

References (44)

1. Adhikari R, Gunatillake PA, Griffiths I, et al. 2008; Biodegradable injectable polyurethanes: synthesis and evaluation for orthopaedic applications. Biomaterials 29: 3762-3770.
2. Baek KH, Lee WY, Oh KW, et al. 2005; The effect of simvastatin on the proliferation and differentiation of human bone marrow stromal cells. J Korean Med Sci 20: 438-444.
3. Benoit DS, Nuttelman CR, Collins SD, et al. 2006; Synthesis and characterization of a fluvastatin-releasing hydrogel delivery system to modulate hMSC differentiation and function for bone regeneration. Biomaterials 27: 6102-6110.
4. Betz OB, Betz VM, Nazarian A, et al. 2006; Direct percutaneous gene delivery to enhance healing of segmental bone defects. J Bone Joint Surg Am 88: 355-365.
5. Brown KV, Li B, Guda T, et al. 2011; Improving bone formation in a rat femur segmental defect by controlling bone morphogenetic protein-2 release. Tissue Eng Part A 17: 1735-1746.
6. Dumas JE, Zienkiewicz K, Tanner SA, et al. 2010; Synthesis and characterization of an injectable allograft bone/polymer composite bone void filler with tunable mechanical properties. Tissue Eng Part A 16: 2505-2518.
7. Enneking WF, Eady JL, Burchardt H. 1980; Autogenous cortical bone grafts in the reconstruction of segmental skeletal defects. J Bone Joint Surg Am 62: 1039-1058.
8. Finkemeier CG. 2002; Bone-grafting and bone-graft substitutes. J Bone Joint Surg Am 84A: 454-464.
9. Fujimoto KL, Guan J, Oshima H, et al. 2007; In vivo evaluation of a porous, elastic, biodegradable patch for reconstructive cardiac procedures. Ann Thorac Surg 83: 648-654.
10. Fukuyama R, Fujita T, Azuma Y, et al. 2004; Statins inhibit osteoblast migration by inhibiting Rac-Akt signaling. Biochem Biophys Res Commun 315: 636-642.
11. Garrett IR, Gutierrez G, Mundy GR. 2001; Statins and bone formation. Curr Pharm Des 7: 715-736.
12. Garrett IR, Gutierrez GE, Rossini G, et al. 2007; Locally delivered lovastatin nanoparticles enhance fracture healing in rats. J Orthop Res 25: 1351-1357.
13. Giannoudis PV, Dinopoulos H, Tsiridis E. 2005; Bone substitutes: an update. Injury 36(suppl 3): S20-S27.
14. Gorna K, Gogolewski S. 2003; Preparation, degradation, and calcification of biodegradable polyurethane foams for bone graft substitutes. J Biomed Mater Res A 67: 813-827.
15. Guan J, Sacks MS, Beckman EJ, et al. 2002; Synthesis, characterization, and cytocompatibility of elastomeric, biodegradable poly(ester-urethane) ureas based on poly(caprolactone) and putrescine. J Biomed Mater Res 61: 493-503.
16. Guelcher S, Srinivasan A, Hafeman A, et al. 2007; Synthesis, in vitro degradation, and mechanical properties of two-component poly(ester urethane) urea scaffolds: effects of water and polyol composition. Tissue Eng 13: 2321-2333.
17. Guelcher SA, Patel V, Gallagher KM, et al. 2006; Synthesis and in vitro biocompatibility of injectable polyurethane foam scaffolds. Tissue Eng 12: 1247-1259.
18. Guelcher SA. 2008; Biodegradable polyurethanes: synthesis and applications in regenerative medicine. Tissue Eng Part B Rev 14: 3-17.
19. Hafeman AE, Li B, Yoshii T, et al. 2008; Injectable biodegradable polyurethane scaffolds with release of platelet-derived growth factor for tissue repair and regeneration. Pharm Res 25: 2387-2399.
20. Hafeman AE, Zienkiewicz KJ, Zachman AL, et al. 2011; Characterization of the degradation mechanisms of lysine-derived aliphatic poly(ester urethane) scaffolds. Biomaterials 32: 419-429.
21. Ho MH, Chiang CP, Liu YF, et al. 2011; Highly efficient release of lovastatin from poly(lactic-co-glycolic acid) nanoparticles enhances bone repair in rats. J Orthop Res 29: 1504-1510.
22. Karp JM, Rzeszutek K, Shoichet MS, et al. 2003; Fabrication of precise cylindrical three-dimensional tissue engineering scaffolds for in vitro and in vivo bone engineering applications. J Craniofac Surg 14: 317-323.
23. Kempen DH, Lu L, Heijink A, et al. 2009; Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration. Biomaterials 30: 2816-2825.
24. Li B, Davidson JM, Guelcher SA. 2009a; The effect of the local delivery of platelet-derived growth factor from reactive two-component polyurethane scaffolds on the healing in rat skin excisional wounds. Biomaterials 30: 3486-3494.
25. Li B, Yoshii T, Hafeman AE, et al. 2009b; The effects of rhBMP-2 released from biodegradable polyurethane/microsphere composite scaffolds on new bone formation in rat femora. Biomaterials 30: 6768-6779.
26. Liao JK, Laufs U. 2005; Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol 45: 89-118.
27. Maeda T, Matsunuma A, Kawane T, et al. 2001; Simvastatin promotes osteoblast differentiation and mineralization in MC3T3-E1 cells. Biochem Biophys Res Commun 280: 874-877.
28. Maeda T, Matsunuma A, Kurahashi I, et al. 2004; Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells. J Cell Biochem 92: 458-471.
29. Mundy G, Garrett R, Harris S, et al. 1999; Stimulation of bone formation in vitro and in rodents by statins. Science 286: 1946-1949.
30. Nyan M, Sato D, Oda M, et al. 2007; Bone formation with the combination of simvastatin and calcium sulfate in critical-sized rat calvarial defect. J Pharmacol Sci 104: 384-386.
31. Nyan M, Miyahara T, Noritake K, et al. 2010; Molecular and tissue responses in the healing of rat calvarial defects after local application of simvastatin combined with α-tricalcium phosphate. J Biomed Mater Res B Appl Biomater 93: 65-73.
32. Omar MA, Wilson JP. 2002; FDA adverse event reports on statin-associated rhabdomyolysis. Ann Pharmacother 36: 288-295.
33. Pauly S, Luttosch F, Morawski M, et al. 2009; Simvastatin locally applied from a biodegradable coating of osteosynthetic implants improves fracture healing comparable to BMP-2 application. Bone 45: 505-511.
34. Perry CR. 1999; Bone repair techniques, bone graft, and bone graft substitutes. Clin Orthop Relat Res 360: 71-86.
35. Schachter M. 2005; Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol 19: 117-125.
36. Seeherman H, Li R, Bouxsein M, et al. 2006; rhBMP-2/calcium phosphate matrix accelerates osteotomy-site healing in a nonhuman primate model at multiple treatment times and concentrations. J Bone Joint Surg Am 88: 144-160.
37. Stein D, Lee Y, Schmid MJ, et al. 2005; Local simvastatin effects on mandibular bone growth and inflammation. J Periodontol 76: 1861-1870.
38. Wong RW, Rabie AB. 2003; Statin collagen grafts used to repair defects in the parietal bone of rabbits. Br J Oral Maxillofac Surg 41: 244-248.
39. Wong RW, Rabie AB. 2005; Histologic and ultrastructural study on statin graft in rabbit skulls. J Oral Maxillofac Surg 63: 1515-1521.
40. Yoshii T, Sotome S, Torigoe I, et al. 2009; Fresh bone marrow introduction into porous scaffolds using a simple low-pressure loading method for effective osteogenesis in a rabbit model. J Orthop Res 27: 1-7.
41. Yoshii T, Hafeman AE, Nyman JS, et al. 2010; A sustained release of lovastatin from biodegradable, elastomeric polyurethane scaffolds for enhanced bone regeneration. Tissue Eng Part A 16: 2369-2379.
42. Younger EM, Chapman MW. 1989; Morbidity at bone graft donor sites. J Orthop Trauma 3: 192-195.
43. Zhang JY, Beckman EJ, Hu J, et al. 2002; Synthesis, biodegradability, and biocompatibility of lysine diisocyanate-glucose polymers. Tissue Eng 8: 771-785.
44. Zhao M, Ko SY, Liu JH, et al. 2009; Inhibition of microtubule assembly in osteoblasts stimulates bone morphogenetic protein 2 expression and bone formation through transcription factor Gli2. Mol Cell Biol 29: 1291-1305.