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

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.

Tissue-engineered vascular grafts for congenital cardiac disease: Clinical experience and current status

“…In the ovine model, electrospinning mandrels were 3D printed based on preoperative imaging, and TEVG scaffolds were then electrospun around the mandrels. [40] These TEVGs demonstrated satisfactory remodeling at six months postoperatively, with histology and mechanical properties similar to the native IVC. There is still work to be done before this technology is ready for translation to the clinic, but we anticipate a future in which a patient’s preoperative imaging will be used to design and print a unique scaffold for his or her surgical reconstruction.…”

The use of 3D printing in cardiac surgery

“…This is especially difficult as no two patients have identical anatomy, not only the intracardiac anatomy, but also the extracardiac anatomy (14), such as the chest wall and the relation of the heart to the chest wall. Taking patient specificity into account using 3D printing technology is thus very relevant and recent papers have reported useful applications (13)(14)(15)(16). Chen et al should be congratulated for their valuable use of 3D printing technology to aid in the surgical treatment of complex aortic disease with a good outcome.…”

Recreating the inferior vena cava with a patient-specific biodegradable conduit

“…In this issue, Fukunishi and colleagues 1 describe a custom-fabricated biodegradable tube graft specifically de- signed for inferior vena cava interposition in Fontan-type operations, which has the potential to alleviate many of the risks associated with traditional grafts. This group’s experience with similar devices actually dates back to 2001, 2 when an obstructed hepatopulmonary conduit was replaced with an absorbable tubular scaffold seeded with autologous mononuclear cells.…”

“…Although it builds on previous experience, the current ovine model of Fukunishi and colleagues 1 marks a distinctly new stage in the evolution of tissue-engineered vascular grafts. First, this graft is custom spun according to patient-specific imaging data, which will allow careful fitting to complex anatomy and may even provide a plat- form by which computational fluid dynamics analysis may be used to optimize cavopulmonary flow patterns for a particular patient.…”

“…Second, the graft is no longer seeded in advance with cellular material. Despite this seemingly fundamental change in preparation, Fukunishi and col- leagues 1 provide histologic evidence both of well- organized cellular replacement of the scaffold material and of acceptable strength and flow characteristics at 6-month follow-up, with no long-term requirement for anti- coagulation. Safely eliminating the laboratory expertise, patient discomfort, storage limitations, and cost associated with stem cell isolation and seeding would allow what was once a niche product fabricated ad hoc at a research institution to become readily available at any hospital.…”