title: Development of a new pre-vascularized tissue-engineered construct using pre-differentiated rADSCs, arteriovenous vascular bundle and porous nano-hydroxyapatide-polyamide 66 scaffold.
abstract: BACKGROUND
  Development of a pre-vascularized tissue-engineered construct with intrinsic vascular system for cell growth and tissue formation still faces many difficulties due to the complexity of the vascular network of natural bone tissue. The present study was to design and form a new vascularized tissue-engineered construct using pre-differentiated rADSCs, arteriovenous vascular bundle and porous nHA-PA 66 scaffold.
  
  
  METHODS
  rADSCs were pre-differentiated to endothelial cells (rADSCs-Endo) and then incorporated in nHA-PA 66 scaffolds in vitro. Subsequently, in vivo experiments were carried out according to the following groups: Group A (rADSCs-Endo/nHA-PA 66 scaffold with arteriovenous vascular bundle), Group B (rADSCs/nHA-PA 66 scaffold with arteriovenous vascular bundle); Group C (nHA-PA66 scaffold with arteriovenous vascular bundle), Group D (nHA-PA 66 scaffold only). The vessel density and vessel diameter were measured based on histological and immunohistochemical evaluation, furthermore, the VEGF-C, FGF-2 and BMP-2 protein expressions were also evaluated by western blot analysis.
  
  
  RESULTS
  The results of in vivo experiments showed that the vessel density and vessel diameter in group A were significantly higher than the other three groups. Between Group B and C, no statistical difference was observed at each time point. In accordance with the results, there were dramatically higher expressions of VEGF-C and FGF-2 protein in Group A than that of Group B, C and D at 2 or 4 weeks. Statistical differences were not observed in VEGF-C and FGF-2 expression between Group B and C. BMP-2 was not expressed in any group at each time point.
  
  
  CONCLUSIONS
  Compared with muscular wrapping method, arteriovenous vascular bundle implantation could promote vascularization of the scaffold; and the angiogenesis of the scaffold was significantly accelerated when pre-differentiated rADSCs (endothelial differentiation) were added. These positive results implicate the combination of pre-differentiated rADSCs (endothelial differentiation) and arteriovenous vascular bundle may achieve rapidly angiogenesis of biomaterial scaffold.
authors.forename: Pei
authors.initials: P
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Jacson
authors.initials: J
authors.lastname: Shen
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Wang
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Dang
authors.forename: Henry
authors.initials: H
authors.lastname: Mankin
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Duan
authors.affiliation: Department of Orthopaedics, Second Affiliated Hospital of Medical College of Xi'an Jiaotong University, No, 157 Xiwu Road, 710004 Xi'an, Shaanxi, China. kunzhengwang@126.com.
authors.forename: Kunzheng
authors.initials: K
authors.lastname: Wang
mesh_terms: D000273:Adipose Tissue; D000818:Animals; D001808:Blood Vessels / Q000637:transplantation*; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D002454:Cell Differentiation; D042783:Endothelial Cells / Q000166:cytology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005434:Flow Cytometry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D018919:Neovascularization, Physiologic; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D042582:Vascular Endothelial Growth Factor C; D016222:Fibroblast Growth Factor 2