Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs

Abstract

There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

Keywords: 3D printing; additive manufacturing; bioink; endothelial cells; vascular graft; vascularized tissue construct.

FIG. 1.

(A) A hybrid vascular graft consisting of an electrospun PLLA scaffold and a printed PCL coating and its use as an in vivo aortic vascular model, (B) a CAD model and a resulting PCL vascular tree with and without a PVA support, (C) a CAD model of GelMA-gellan hydrogel tube supported with PCL fibers and an alginate support structure and the resulting tube without supports. CAD, computer-aided design; GelMA, methacrylated gelatin; PCL, poly(ɛ-caprolactone); PLLA, poly(l-lactide); PVA, polyvinyl alcohol. (Reproduced with the permission from (A) IOP Publishing Ltd. and Libertas Academica, (B, C) IOP Publishing Ltd.)

FIG. 2.

(A, B) A picture of a SLA-fabricated vascular tube^, and (C, D) a scanning electron microscope image of a microcapillary structure fabricated by 2PP.^, 2PP, two-photon polymerization; SLA, stereolithography. (Reproduced with the permission from (A) IOP Publishing Ltd., (B, C) Molecular Diversity Preservation International, and (D) John Wiley & Sons, Inc.)

FIG. 3.

Bioprinting of (A) cell-laden alginate/gelatin aortic valve conduits and (B) glioma cell-laden alginate tubes. (Reproduced with the permission from (A) John Wiley & Sons, Inc. and (B) IOP Publishing Ltd. All rights reserved.)

FIG. 4.

(A) A coaxial nozzle, a hollow alginate fiber, and a multilayer construct of hollow fibers, (B) a multilayer construct of EC-laden fibers to form endothelialized vascular channels, and (C) a hollow alginate fiber scaffold. EC, endothelial cell. (Reproduced with the permission from (A) IOP Publishing Ltd. and (B, C) John Wiley & Sons, Inc.)

FIG. 5.

HUVECs seeded on channels in a matrix based on (A) fibroblast-laden fibrin, (B) acellular GelMA, and (C) fibrin/gelatin hydrogel. HUVECs, human umbilical vein endothelial cells; SMCs, smooth muscle cells. (Reproduced with the permission from (A) Nature Publishing Group, (B) John Wiley & Sons, Inc., and (C) PNAS.)

FIG. 6.

Organ-on-a-chip tissue models with built-in vasculatures and computer-modeled microholes to allow for molecular exchange and tissue ingrowth. (Reproduced with the permission from Nature Publishing Group.)

FIG. 7.

(A) Biodegradable hydrogel grafts printed with SLA and (B) multimaterial constructs composed of a hydrogel tube inside a scaffold as printed with a hybrid system of FDM and SLA. FDM, fused deposition modeling. (Reproduced with the permission from (A) The Royal Society of Chemistry and (B) IOP Publishing Ltd.)