Angiogenic response to bioactive glass promotes bone healing in an irradiated calvarial defect.
Localized radiation is an effective treatment modality for carcinomas, yet the associated reduction of the host vasculature significantly inhibits the tissue's regenerative capacity. Low concentrations of bioactive glass (BG) possess angiogenic potential, and we hypothesized that localized BG presentation would increase neovascularization and promote healing in an irradiated bone defect. An isolated calvarial region of Sprague-Dawley rats was irradiated 2 weeks before surgery. Bilateral critical-sized defects were created and immediately filled with a BG-loaded collagen sponge or an empty sponge as an internal control. Histological analysis of calvaria collected after 2 weeks demonstrated greater neovascularization within the defect in the presence of BG than with collagen alone. Noninvasive ultrasound imaging at 4 weeks detected less contrast agent in the brain below BG-treated defects than in the nearby untreated defects and images of treated defects acquired at 2 weeks. The reduced ability to detect contrast agent in BG-treated defects suggested greater attenuation of ultrasound signal due to early bone formation. Micro-computed tomography imaging at 12 weeks demonstrated significantly greater bone volume fraction within BG-treated defects than in controls. These results suggest that neovascularization induced by localized BG delivery promotes bone regeneration in this highly compromised model of bone healing and may offer an alternative approach to costly growth factors and their potential side-effects.
Leu
Ann
A
Department of Biomedical Engineering, University of California at Davis, Davis, California, USA.
Stieger
Susanne M
SM
Dayton
Paul
P
Ferrara
Katherine W
KW
Leach
J Kent
JK
D000818:Animals; D001672:Biocompatible Materials / Q000627:therapeutic use*; D001861:Bone Regeneration / Q000187:drug effects*; D018786:Bone Substitutes / Q000627:therapeutic use*; D002516:Ceramics / Q000627:therapeutic use*; D003094:Collagen / Q000627:therapeutic use; D048091:Guided Tissue Regeneration / Q000379:methods*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000098:blood supply / Q000601:surgery*; D014057:Tomography, X-Ray Computed; D014945:Wound Healing / Q000187:drug effects*
D001672:Biocompatible Materials; C022107:Bioglass; D018786:Bone Substitutes; D003094:Collagen
Tissue Eng. 2005 May-Jun;11(5-6):768-77
15998217
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9656-61
12118119
Expert Rev Mol Diagn. 2005 May;5(3):447-55
15934820
J Craniofac Surg. 1998 Mar;9(2):131-7
9586541
J Oral Maxillofac Surg. 2005 Sep;63(9):1310-6
16122595
Biomaterials. 2005 Jul;26(19):4171-9
15664644
Biochem Biophys Res Commun. 1994 Feb 28;199(1):380-6
8123039
J Cell Biochem. 2000 Sep 14;79(4):672-85
10996857
Nat Biotechnol. 2001 Nov;19(11):1029-34
11689847
Circulation. 2005 Jun 21;111(24):3248-54
15956135
Surgery. 2001 May;129(5):552-8
11331447
Endocrinology. 2000 May;141(5):1667-74
10803575
Med Biol Eng Comput. 2007 May;45(5):421-35
17340155
Biotechnol Bioeng. 2007 Sep 1;98(1):271-81
17657771
Hum Gene Ther. 2003 Jul 20;14(11):1107-15
12885349
Bone. 2002 Mar;30(3):472-7
11882460
Int J Radiat Oncol Biol Phys. 1998 Nov 1;42(4):885-9
9845115
Int J Cardiol. 2006 Oct 26;113(1):19-24
16338011
J Bone Miner Res. 2006 May;21(5):735-44
16734388
Cancer Res. 2007 Mar 1;67(5):2040-5
17332332
FASEB J. 2005 Apr;19(6):665-7
15677693
J Clin Oncol. 2005 Feb 10;23(5):1011-27
15585754
J Dent Res. 2006 Jul;85(7):633-7
16798864
J Histochem Cytochem. 2002 Mar;50(3):333-40
11850436
Expert Opin Biol Ther. 2004 Jul;4(7):1015-27
15268670
Plast Reconstr Surg. 2000 Oct;106(5):1049-61
11039376
Biomaterials. 2004 Dec;25(27):5857-66
15172498
J Orthop Res. 2008 Apr;26(4):522-30
17985393
J Biol Chem. 1995 Dec 29;270(52):31189-95
8537383
Bone. 2004 Aug;35(2):562-9
15268909
J Mater Sci Mater Med. 2007 Feb;18(2):255-63
17323156
Clin Orthop Relat Res. 1996 Aug;(329):300-9
8769465
Pharm Res. 2008 May;25(5):1222-9
18049878
Ultrasound Med Biol. 2006 May;32(5):673-81
16677927
J Dent Res. 2004 Mar;83(3):204-10
14981120
J Clin Invest. 2002 Sep;110(6):751-9
12235106
Pediatr Transplant. 2007 Jun;11(4):379-87
17493217
Biomaterials. 2006 Jun;27(17):3249-55
16490250
J Bone Joint Surg Am. 2002 Jun;84(6):1032-44
12063342
Eur Radiol. 2004 Oct;14 Suppl 8:P4-10
15700327
J Tissue Eng Regen Med. 2007 Jul-Aug;1(4):318-21
18038423
Drug Discov Today. 2003 Nov 1;8(21):980-9
14643161
Lancet Oncol. 2003 Sep;4(9):529-36
12965273
Cancer Res. 2003 Jul 1;63(13):3755-63
12839971
Laryngoscope. 2005 Jul;115(7):1170-7
15995502