Review: advances in vascular tissue engineering using protein-based biomaterials

Abstract

The clinical need for improved blood vessel substitutes, especially in small-diameter applications, drives the field of vascular tissue engineering. The blood vessel has a well-characterized structure and function, but it is a complex tissue, and it has proven difficult to create engineered tissues that are suitable for widespread clinical use. This review is focused on approaches to vascular tissue engineering that use proteins as the primary matrix or "scaffold" material for creating fully biological blood vessel replacements. In particular, this review covers four main approaches to vascular tissue engineering: 1) cell-populated protein hydrogels, 2) cross-linked protein scaffolds, 3) decellularized native tissues, and 4) self-assembled scaffolds. Recent advances in each of these areas are discussed, along with advantages of and drawbacks to these approaches. The first fully biological engineered blood vessels have entered clinical trials, but important challenges remain before engineered vascular tissues will have a wide clinical effect. Cell sourcing and recapitulating the biological and mechanical function of the native blood vessel continue to be important outstanding hurdles. In addition, the path to commercialization for such tissues must be better defined. Continued progress in several complementary approaches to vascular tissue engineering is necessary before blood vessel substitutes can achieve their full potential in improving patient care.

FIG. 1

Schematic of structure of a medium-sized blood vessels, showing the main cellular, extracellular matrix, and environmental components (not to scale). Color images available online at www.liebertpub.com/ten.

FIG. 2

Image of a collagen type I hydrogel construct containing vascular smooth muscle cells after 7 days in static culture. Color images available online at www.liebertpub.com/ten.

FIG. 3

Scanning electron microscope images of protein hydrogel matrices: (A) collagen type I, (B) fibrin, (C) collagen–fibrin composite (scale bar 300 nm).

FIG. 4

Example of a bioreactor system used to mechanically stimulate engineered vascular tissues in vitro: (A) three-module bioreactor showing lumen and external flow direction (arrows), (B) schematic of bioreactor flow circuit during construct culture. (Used by permission from Williams, C., and Wick, T.M. Perfusion bioreactor for small diameter tissue-engineered arteries. Tissue Eng 10, 930, 2004.)

FIG. 5

Scanning electron microscope images of (A) electrospun type I collagen, (B) electrospun elastin (scale bar = 1 micron in both panels). (Used by permission from Boland, E.D., Matthews, J.A., Pawlowski, K.J., Simpson, D.G., Wnek, G.E., and Bowlin, G.L. Electrospinning collagen and elastin: preliminary vascular tissue engineering. Front Biosci 9, 1422, 2004.)

FIG. 6

Scanning electron microscope image of decellularized elastin scaffold (scale bar 100 nm). (Used by permission from Lu, Q., Ganesan, K., Simionescu, D.T., and Vyavahare, N.R. Novel porous aortic elastin and collagen scaffolds for tissue engineering. Biomaterials 25, 5227, 2004.)

FIG. 7

Hematoxylin and eosin staining of (A) native porcine carotid artery, (B) collagen hydrogel construct, (C) hybrid construct with elastin sleeve and collagen hydrogel. (Used by permission from Berglund, J.D., Nerem, R.M., and Sambanis, A. Viscoelastic testing methodologies for tissue engineered blood vessels. Tissue Eng 10, 1526, 2004.)

FIG. 8

Hematoxylin and eosin–stained longitudinal section of tube of granulation tissue after 2 weeks of growth in a rat. Arrow indicates side from which silicone tubing was removed (magnification ×300). (Used by permission from Campbell, J.H., Efendy, J.L., and Campbell, G.R. Novel vascular graft grown within recipient's own peritoneal cavity. Circ Res 85, 1173, 1999.) Color images available online at www.liebertpub.com/ten.