Three-dimensional customized artificial grafts functionalized with biomimetic softness and anticoagulant heparin-dopamine surface modification: Preclinical study for practical applications.

Abstract

Artificial vascular grafts, as blood vessel substitutes, are a prime challenge in tissue engineering and biomaterial research. An ideal artificial graft must have physiological and mechanical properties similar to those of a natural blood vessel, and hemocompatibility on its surface. We designed and fabricated artificial grafts by applying 3D printing and templated technology, which is endowed with morphologically patient-specific vascular reconstruction. To optimize mechanical properties, the graft wall was engineered with a controllable hybrid porous structure through a multilayer combination of porous and nonporous coatings, thereby achieving biomimetic mechanical flexibility with reduced stiffness. Further, we successfully synthesized dopamine-conjugated heparin (Hep-DA) utilizing carbodiimide chemistry, and coated it on a 3D porous graft to improve both surface adhesion and anticoagulant ability. The Hep-DA-coated 3D graft did not show significant cytotoxic effects with a long-term sustained heparin release. We performed a preclinical study in swine using the developed graft along with commercially available graft ePTFE and Dacron as a reference. They were implanted in the swine aorta for 28 days and the implanted grafts were harvested for further analysis. Histopathology study results showed the feasibility of the developed artificial vascular grafts that have less calcification, fibrosis, and collagen deposition than commercially available grafts.