title: Angiogenesis and bone regeneration of porous nano-hydroxyapatite/coralline blocks coated with rhVEGF165 in critical-size alveolar bone defects in vivo.
abstract: To improve the regenerative performance of nano-hydroxyapatite/coralline (nHA/coral) block grafting in a canine mandibular critical-size defect model, nHA/coral blocks were coated with recombinant human vascular endothelial growth factor(165) (rhVEGF) via physical adsorption (3 μg rhVEGF165 per nHA/coral block). After the nHA/coral blocks and VEGF/nHA/coral blocks were randomly implanted into the mandibular box-shaped defects in a split-mouth design, the healing process was evaluated by histological observation and histomorphometric and immunohistological analyses. The histological evaluations revealed the ingrowth of newly formed blood vessels and bone at the periphery and cores of the blocks in both groups at both 3 and 8 weeks postsurgery, respectively. In the histomorphometric analysis, the VEGF/nHA/coral group exhibited a larger quantity of new bone formation at 3 and 8 weeks postsurgery. The percentages of newly formed bone within the entire blocks in the VEGF/nHA/coral group were 27.3% ± 8.1% and 39.3% ± 12.8% at 3 weeks and 8 weeks, respectively, and these values were slightly greater than those of the nHA/coral group (21.7% ± 3.0% and 32.6% ± 10.3%, respectively), but the differences were not significant (P>0.05). The immunohistological evaluations revealed that the neovascular density in the VEGF/nHA/coral group (146 ± 32.9 vessel/mm(2)) was much greater than that in the nHA/coral group (105 ± 51.8 vessel/mm(2)) at the 3-week time point (P<0.05), but no significant difference was observed at the 8-week time point (341 ± 86.1 and 269 ± 50.7 vessel/mm(2), respectively, P>0.05). The present study indicated that nHA/coral blocks might be optimal scaffolds for block grafting in critical-size mandibular defects and that additional VEGF coating via physical adsorption can promote angiogenesis in the early stage of bone healing, which suggests that prevascularized nHA/coral blocks have significant potential as a bioactive material for bone regeneration in large-scale alveolar defects.
authors.affiliation: Department of Oral Implantology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China ; Center of Stomatology, The First People's Hospital of Foshan, Foshan, Guangdong, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Du
authors.affiliation: Department of Oral Implantology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Oral Implantology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China ; Department of Oral and Maxillofacial Surgery, Qingdao Stomatological Hospital, Qingdao, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Oral Implantology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Shaobing
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, People's Republic of China.
authors.forename: Xiangning
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Oral Implantology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Oral Implantology, Guangdong Provincial Stomatological Hospital, Southern Medical University, Guangzhou, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002516:Ceramics / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry / Q000627:therapeutic use; D006882:Hydroxyapatites / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008334:Mandible / Q000187:drug effects; D008338:Mandibular Injuries / Q000188:drug therapy; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D016062:Porosity; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D043925:Angiogenesis Inducing Agents; D004337:Drug Carriers; D006882:Hydroxyapatites; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C119955:coralline hydroxyapatite
keywords: angiogenesis; block grafting; bone defect; bone regeneration; critical size; nano- hydroxyapatite/coralline; tissue engineering
references.citation: Biomaterials. 2005 Mar;26(7):697-702
references.pmid: 15350773
references.citation: Eur J Orthop Surg Traumatol. 2013 Oct;23(7):767-74
references.pmid: 23412202
references.citation: Clin Oral Implants Res. 2008 Jul;19(7):642-52
references.pmid: 18492078
references.citation: Biomed Mater. 2011 Feb;6(1):015013
references.pmid: 21252414
references.citation: J Control Release. 2006 Jan 10;110(2):260-265
references.pmid: 16313993
references.citation: J Biomed Mater Res A. 2003 Aug 1;66(2):283-91
references.pmid: 12888998
references.citation: J Biomed Mater Res A. 2003 Jun 15;65(4):447-53
references.pmid: 12761834
references.citation: Biomaterials. 2013 Jul;34(21):4971-81
references.pmid: 23566802
references.citation: Int J Oral Maxillofac Implants. 2013 Sep-Oct;28(5):1370-6
references.pmid: 24066330
references.citation: J Biomed Mater Res A. 2010 Dec 1;95(3):964-72
references.pmid: 20824650
references.citation: Biomaterials. 2009 May;30(14):2675-82
references.pmid: 19187958
references.citation: J Biomech. 2011 Jun 3;44(9):1793-6
references.pmid: 21549380
references.citation: Tissue Eng. 2005 Mar-Apr;11(3-4):609-17
references.pmid: 15869437
references.citation: J Biomed Mater Res B Appl Biomater. 2009 Jul;90(1):116-22
references.pmid: 19016454
references.citation: J Biomed Mater Res A. 2010 Mar 15;92(4):1256-64
references.pmid: 19322875
references.citation: Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9656-61
references.pmid: 12118119
references.citation: Biomaterials. 2005 Sep;26(27):5474-91
references.pmid: 15860204
references.citation: Biomaterials. 2003 Dec;24(27):4987-97
references.pmid: 14559012
references.citation: Braz Dent J. 2003;14(2):119-24
references.pmid: 12964656
references.citation: Tissue Eng Part A. 2009 Sep;15(9):2347-62
references.pmid: 19249918
references.citation: J Mater Sci Mater Med. 2012 Apr;23(4):1073-84
references.pmid: 22311076
references.citation: J Biomater Appl. 2004 Oct;19(2):107-20
references.pmid: 15381784
references.citation: J Biomed Mater Res A. 2007 May;81(2):474-83
references.pmid: 17133509
references.citation: J Biomed Mater Res A. 2003 Sep 15;66(4):747-54
references.pmid: 12926025
references.citation: Tissue Eng. 2003 Apr;9(2):327-36
references.pmid: 12740095
references.citation: Int J Oral Maxillofac Surg. 2007 Jan;36(1):39-44
references.pmid: 17005372
references.citation: Biophys J. 2007 Aug 1;93(3):750-9
references.pmid: 17617550
references.citation: Periodontal Clin Investig. 1996 Fall;18(2):13-6
references.pmid: 9116465
references.citation: J Clin Periodontol. 2009 Mar;36(3):258-64
references.pmid: 19236538
references.citation: J Biomed Mater Res A. 2008 Jun 1;85(3):777-86
references.pmid: 17896777
references.citation: Tissue Eng Part A. 2008 Aug;14(8):1331-40
references.pmid: 18601588
references.citation: Biomaterials. 2002 May;23(9):2063-70
references.pmid: 11996048
references.citation: J Biomed Mater Res A. 2012 Nov;100(11):3143-50
references.pmid: 22826183
references.citation: J Periodontol. 2003 Jul;74(7):957-64
references.pmid: 12931757
references.citation: J Clin Periodontol. 2005 Jan;32(1):104-10
references.pmid: 15642067
references.citation: Cell Tissue Res. 2010 Apr;340(1):169-77
references.pmid: 20198386
references.citation: Clin Oral Implants Res. 2010 Sep;21(9):904-12
references.pmid: 20491835
references.citation: J Biomed Mater Res A. 2010 Feb;92(2):626-40
references.pmid: 19235222
references.citation: J Clin Periodontol. 2009 Dec;36(12):1067-74
references.pmid: 19929958
references.citation: J Biomed Mater Res A. 2010 Mar 1;92(3):953-62
references.pmid: 19291690
references.citation: Oral Maxillofac Surg. 2008 Jul;12(2):73-8
references.pmid: 18618164
references.citation: Biomaterials. 2006 Jun;27(17):3249-55
references.pmid: 16490250
references.citation: Tissue Eng Part A. 2012 Jun;18(11-12):1239-52
references.pmid: 22320360
references.citation: J Biomed Mater Res B Appl Biomater. 2012 Oct;100(7):1782-91
references.pmid: 22807331
references.citation: J Biomater Appl. 2007 Nov;22(3):223-39
references.pmid: 17255157