title: Well-organized neointima of large-pore poly(L-lactic acid) vascular graft coated with poly(L-lactic-co-ε-caprolactone) prevents calcific deposition compared to small-pore electrospun poly(L-lactic acid) graft in a mouse aortic implantation model.
abstract: OBJECTIVE
  Tissue engineering techniques have emerged that allow bioresorbable grafts to be implanted that restore function and transform into biologically active arteries. However, these implants are susceptible to calcification during the remodeling process. The objective of this study was to evaluate the role of pore size of bioabsorbable grafts in the development of calcification.
  
  
  METHODS
  Two types of grafts were prepared: a large-pore graft constructed of poly(L-lactic acid) (PLA) fibers coated with poly(L-lactide-co-ε-caprolactone) (PLCL) (PLA-PLCL), and a small-pore graft made of electrospun PLA nanofibers (PLA-nano). Twenty-eight PLA-PLCL grafts and twenty-five PLA-nano grafts were implanted as infra-renal aortic interposition conduits in 8-week-old female SCID/Bg mice, and followed for 12 months after implantation.
  
  
  RESULTS
  Large-pore PLA-PLCL grafts induced a well-organized neointima after 12 months, and Alizarin Red S staining showed neointimal calcification only in the thin neointima of small-pore PLA-nano grafts. At 12 months, macrophage infiltration, evaluated by F4/80 staining, was observed in the thin neointima of the PLA-nano graft, and there were few vascular smooth muscle cells (VSMCs) in this layer. On the other hand, the neointima of the PLA-PLCL graft was composed of abundant VSMCs, and a lower density of macrophages (F4/80 positive cells, PLA-PLCL; 68.1 ± 41.4/mm(2) vs PLA-nano; 188.3 ± 41.9/mm(2), p = 0.007). The VSMCs of PLA-PLCL graft expressed transcription factors of both osteoblasts and osteoclasts.
  
  
  CONCLUSIONS
  These findings demonstrate that in mouse arterial circulation, large-pore PLA-PLCL grafts created a well-organized neointima and prevented calcific deposition compared to small-pore, electrospun PLA-nano grafts.
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tara
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Kurobe
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Rocco
authors.affiliation: Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Maxfield
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Cameron A
authors.initials: CA
authors.lastname: Best
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Tai
authors.initials: T
authors.lastname: Yi
authors.affiliation: Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Breuer
authors.affiliation: Tissue Engineering Program and Surgical Research, Nationwide Children's Hospital, Columbus, OH, USA; Department of Cardiothoracic Surgery, The Heart Center, Nationwide Children's Hospital, Columbus, OH, USA. Electronic address: toshiharu.shinoka@nationwidechildrens.org.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Shinoka
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism; D002114:Calcinosis / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000473:pathology; D019344:Lactic Acid / Q000737:chemistry*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D008855:Microscopy, Electron, Scanning; D023421:Models, Animal; D058426:Neointima / Q000473:pathology*; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis; D011091:Polyesters / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D023822:Tissue Engineering / Q000379:methods; D014157:Transcription Factors / Q000378:metabolism; D058017:Vascular Grafting / Q000379:methods*
chemical_list: D011091:Polyesters; D011108:Polymers; D014157:Transcription Factors; D019344:Lactic Acid; C033616:poly(lactide); C062968:lactide-caprolactone copolymer; D003094:Collagen; D004549:Elastin
keywords: Atherosclerotic cardiovascular diseases; Bioabsorbable grafts; Calcification; Electrospinning technique; Pore size; Tissue engineering