title: Characterization of the natural history of extracellular matrix production in tissue-engineered vascular grafts during neovessel formation.
abstract: BACKGROUND
  The extracellular matrix (ECM) is a critical determinant of neovessel integrity.
  
  
  METHODS
  Thirty-six (polyglycolic acid + polycaprolactone and poly lactic acid) tissue-engineered vascular grafts seeded with syngeneic bone marrow mononuclear cells were implanted as inferior vena cava interposition grafts in C57BL/6 mice. Specimens were characterized using immunohistochemical staining and qPCR for representative ECM components in addition to matrix metalloproteinases (MMPs). Total collagen, elastin, and glycosaminoglycan (GAG) contents were determined. MMP activity was measured using zymography.
  
  
  RESULTS
  Collagen production on histology demonstrated an initial increase in type III at 1 week followed by type I production at 2 weeks and type IV at 4 weeks. Gene expression of both type I and type III peaked at 2 weeks, whereas type IV continued to increase over the 4-week period. Histology demonstrated fibrillin-1 deposition at 1 week followed by elastin production at 4 weeks. Elastin gene expression significantly increased at 4 weeks, whereas fibrillin-1 decreased at 4 weeks. GAG demonstrated abundant production at each time point on histology. Gene expression of decorin significantly increased at 4 weeks, whereas versican decreased over time. Biochemical analysis showed that total collagen production was greatest at 2 weeks, and there was a significant increase in elastin and GAG production at 4 weeks. Histological characterization of MMPs showed abundant production of MMP-2 at each time point, while MMP-9 decreased over the 4-week period. Gene expression of MMP-2 significantly increased at 4 weeks, whereas MMP-9 significantly decreased at 4 weeks.
  
  
  CONCLUSIONS
  ECM production during neovessel formation is characterized by early ECM deposition followed by extensive remodeling.
authors: Department of Surgery, Yale University School of Medicine, New Haven, Conn., USA.
authors: Yuji
authors: Y
authors: Naito
authors: Misty
authors: M
authors: Williams-Fritze
authors: Daniel R
authors: DR
authors: Duncan
authors: Spencer N
authors: SN
authors: Church
authors: Narutoshi
authors: N
authors: Hibino
authors: Joseph A
authors: JA
authors: Madri
authors: Jay D
authors: JD
authors: Humphrey
authors: Toshiharu
authors: T
authors: Shinoka
authors: Christopher K
authors: CK
authors: Breuer
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D001854:Bone Marrow Cells / Q000166:cytology; D003094:Collagen / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011091:Polyesters / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D058017:Vascular Grafting; D014682:Vena Cava, Inferior / Q000601:surgery*
chemical_list: D011091:Polyesters; D011108:Polymers; C016240:polycaprolactone; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D003094:Collagen; D004549:Elastin; D020782:Matrix Metalloproteinases