title: Preclinical study of patient-specific cell-free nanofiber tissue-engineered vascular grafts using 3-dimensional printing in a sheep model.
abstract: Tissue-engineered vascular grafts (TEVGs) offer potential to overcome limitations of current approaches for reconstruction in congenital heart disease by providing biodegradable scaffolds on which autologous cells proliferate and provide physiologic functionality. However, current TEVGs do not address the diverse anatomic requirements of individual patients. This study explores the feasibility of creating patient-specific TEVGs by combining 3-dimensional (3D) printing and electrospinning technology.
  
  
  
  An electrospinning mandrel was 3D-printed after computer-aided design based on preoperative imaging of the ovine thoracic inferior vena cava (IVC). TEVG scaffolds were then electrospun around the 3D-printed mandrel. Six patient-specific TEVGs were implanted as cell-free IVC interposition conduits in a sheep model and explanted after 6 months for histologic, biochemical, and biomechanical evaluation.
  
  
  
  All sheep survived without complications, and all grafts were patent without aneurysm formation or ectopic calcification. Serial angiography revealed significant decreases in TEVG pressure gradients between 3 and 6 months as the grafts remodeled. At explant, the nanofiber scaffold was nearly completely resorbed and the TEVG showed similar mechanical properties to that of native IVC. Histological analysis demonstrated an organized smooth muscle cell layer, extracellular matrix deposition, and endothelialization. No significant difference in elastin and collagen content between the TEVG and native IVC was identified. There was a significant positive correlation between wall thickness and CD68+macrophage infiltration into the TEVG.
  
  
  
  Creation of patient-specific nanofiber TEVGs by combining electrospinning and 3D printing is a feasible technology as future clinical option. Further preclinical studies involving more complex anatomical shapes are warranted.
authors.affiliation: Department of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, Md.
authors.forename: Takuma
authors.initials: T
authors.lastname: Fukunishi
authors.affiliation: Tissue Engineering and Surgical Research, Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Cameron A
authors.initials: CA
authors.lastname: Best
authors.affiliation: Tissue Engineering and Surgical Research, Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Tadahisa
authors.initials: T
authors.lastname: Sugiura
authors.affiliation: The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Medical Center, Washington, DC.
authors.forename: Justin
authors.initials: J
authors.lastname: Opfermann
authors.affiliation: Department of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, Md.
authors.forename: Chin Siang
authors.initials: CS
authors.lastname: Ong
authors.affiliation: Tissue Engineering and Surgical Research, Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Shinoka
authors.affiliation: Tissue Engineering and Surgical Research, Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Breuer
authors.affiliation: The Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Medical Center, Washington, DC.
authors.forename: Axel
authors.initials: A
authors.lastname: Krieger
authors.affiliation: Nanofiber Solutions Inc, Columbus, Ohio.
authors.forename: Jed
authors.initials: J
authors.lastname: Johnson
authors.affiliation: Department of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, Md. Electronic address: nhibino1@jhmi.edu.
authors.forename: Narutoshi
authors.initials: N
authors.lastname: Hibino
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation / Q000295:instrumentation*; D000072226:Computed Tomography Angiography; D017076:Computer-Aided Design; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D023421:Models, Animal; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D049329:Nanostructures; D036103:Nanotechnology / Q000379:methods*; D058426:Neointima; D010690:Phlebography / Q000379:methods; D066330:Printing, Three-Dimensional; D011474:Prosthesis Design; D034561:Sheep, Domestic; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D014654:Vascular Patency; D066253:Vascular Remodeling; D014682:Vena Cava, Inferior / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D014690:Venous Pressure
keywords: 3D printing; Fontan circulation; cell-free tissue engineering; congenital heart disease; electrospun nanofibers; patient-specific; preclinical study; sheep model; tissue-engineered vascular graft