Preclinical study of patient-specific cell-free nanofiber tissue-engineered vascular grafts using 3-dimensional printing in a sheep model

Takuma Fukunishi, Cameron A. Best, Tadahisa Sugiura, Justin Opfermann, Chin Siang Ong, Toshiharu Shinoka, Christopher K. Breuer, Axel Krieger, Jed Johnson, Narutoshi Hibino

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Original languageEnglish (US)
Pages (from-to)924-932
Number of pages9
JournalJournal of Thoracic and Cardiovascular Surgery
Volume153
Issue number4
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

Fingerprint

Blood Vessel Prosthesis
Nanofibers
Sheep
Inferior Vena Cava
Three Dimensional Printing
Technology
Transplants
Computer-Aided Design
Elastin
Feasibility Studies
Smooth Muscle Myocytes
Aneurysm
Extracellular Matrix
Heart Diseases
Angiography
Collagen
Thorax
Macrophages

Keywords

  • 3D printing
  • cell-free tissue engineering
  • congenital heart disease
  • electrospun nanofibers
  • Fontan circulation
  • patient-specific
  • preclinical study
  • sheep model
  • tissue-engineered vascular graft

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Preclinical study of patient-specific cell-free nanofiber tissue-engineered vascular grafts using 3-dimensional printing in a sheep model. / Fukunishi, Takuma; Best, Cameron A.; Sugiura, Tadahisa; Opfermann, Justin; Ong, Chin Siang; Shinoka, Toshiharu; Breuer, Christopher K.; Krieger, Axel; Johnson, Jed; Hibino, Narutoshi.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 153, No. 4, 01.04.2017, p. 924-932.

Research output: Contribution to journalArticle

Fukunishi, Takuma ; Best, Cameron A. ; Sugiura, Tadahisa ; Opfermann, Justin ; Ong, Chin Siang ; Shinoka, Toshiharu ; Breuer, Christopher K. ; Krieger, Axel ; Johnson, Jed ; Hibino, Narutoshi. / Preclinical study of patient-specific cell-free nanofiber tissue-engineered vascular grafts using 3-dimensional printing in a sheep model. In: Journal of Thoracic and Cardiovascular Surgery. 2017 ; Vol. 153, No. 4. pp. 924-932.
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AU - Opfermann, Justin

AU - Ong, Chin Siang

AU - Shinoka, Toshiharu

AU - Breuer, Christopher K.

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AU - Johnson, Jed

AU - Hibino, Narutoshi

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N2 - Background 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. Methods 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. Results 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. Conclusions 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.

AB - Background 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. Methods 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. Results 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. Conclusions 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.

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