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

被引:81
作者
Fukunishi, Takuma [1 ]
Best, Cameron A. [2 ]
Sugiura, Tadahisa [2 ]
Opfermann, Justin [3 ]
Ong, Chin Siang [1 ]
Shinoka, Toshiharu [2 ]
Breuer, Christopher K. [2 ]
Krieger, Axel [3 ]
Johnson, Jed [4 ]
Hibino, Narutoshi [1 ]
机构
[1] Johns Hopkins Univ Hosp, Dept Cardiac Surg, 1800 Orleans St,Zayed 7107, Baltimore, MD 21287 USA
[2] Nationwide Childrens Hosp, Tissue Engn & Surg Res, Washington, DC USA
[3] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA
[4] Nanofiber Solut Inc, Columbus, OH USA
基金
美国国家卫生研究院;
关键词
3D printing; cell-free tissue engineering; congenital heart disease; electrospun nanofibers; Fontan circulation; patient-specific; preclinical study; sheep model; tissue-engineered vascular graft; EXTRACARDIAC FONTAN OPERATION; ANEURYSM; TOOL;
D O I
10.1016/j.jtcvs.2016.10.066
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:924 / 932
页数:9
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