Abstract
There is a considerable clinical need for alternatives to the autologous vein and artery tissues used for vascular reconstructive surgeries such as CABG, lower limb bypass, arteriovenous shunts and repair of congenital defects to the pulmonary outflow tract. So far, synthetic materials have not matched the efficacy of native tissues, particularly in small diameter applications. The development of cardiovascular tissue engineering introduced the possibility of a living, biological graft that might mimic the functional properties of native vessels. While academic research in the field of tissue engineering in general has been active, as yet there has been no clear example of clinical and commercial success. The recent transition of cell-based therapies from experimental to clinical use has, however, reinvigorated the field of cardiovascular tissue engineering. Here, we discuss the most promising approaches specific to tissue-engineered blood vessels and briefly introduce our recent clinical results. The unique regulatory, reimbursement and production challenges facing personalized medicine are also discussed.
Key Points
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Tissue-engineered blood vessel technologies should target four criteria to maximize the likelihood of clinical success: appropriate burst pressure (>1,700 mmHg); appropriate fatigue resistance (30 days of in vitro cycling under physiological loading without marked dilation); an autologous endothelium; and reproducible demonstration of these characteristics using human cells
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The recent transition to clinical use by two tissue-engineering groups suggests that cell-based therapeutics are clinically viable approaches for patients lacking suitable autologous vein/artery for vascular reconstruction
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To accommodate the increased time and complexity associated with these cell-based solutions, clinicians will have to shift some clinical management decisions from an 'off-the-shelf' reactive strategy toward a more proactive and preventative treatment plan
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Reimbursement models suggest that the efficacy of these costly therapies will have to approach that of native vein to show a cost–benefit relative to other synthetic grafts
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Regulatory challenges could hinder large-scale commercialization of autologous cell-based therapies unless lot release and quality criteria are softened from the current regulations, which are more relevant to the larger batch sizes associated with aseptic drug production or cell-based bioprocessing
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References
Conte MS (1998) The ideal small arterial substitute: a search for the Holy Grail? FASEB J 12: 43–45
Kakisis JD et al. (2005) Artificial blood vessel: the Holy Grail of peripheral vascular surgery. J Vasc Surg 41: 349–354
Veith FJ et al. (1986) Six year prospective multicenter randomized comparison of autologous saphenous vein and expanded polytetrafluoroethylene grafts in infrainguinal arterial reconstructions. J Vasc Surg 3: 104–114
Sapsford RN et al. (1981) Early and late patency of expanded polytetrafluoroethylene vascular grafts in aorta-coronary bypass. J Thorac Cardiovasc Surg 81: 860–864
Klinkert P et al. (2004) Saphenous vein versus PTFE for above-knee femoropopliteal bypass: a review of the literature. Eur J Vasc Endovasc Surg 27: 357–362
US Renal Data System (2003) Annual data report: atlas of end-stage renal disease in the United States. National Institute of Health and of National Institute of Diabetes and Digestive and Kidney Disease, Bethesda, MD, USA
Quiñones-Baldrich WJ et al. (1991) Failure of PTFE infrainguinal revascularization: patterns, management alternatives, and outcome. Ann Vasc Surg 5: 163–169
Seeger JM (2000) Management of patients with prosthetic vascular graft infection. Am Surg 66: 166–177
Sarkar S et al. (2006) The mechanical properties of infrainguinal vascular bypass grafts: their role in influencing patency. Eur J Vasc Endovasc Surg 31: 627–636
Murray-Wijelath J et al. (2004) Vascular graft healing—III: FTIR analysis of ePTFE graft samples from implanted bigrafts. J Biomed Mater Res B Appl Biomater 70: 223–232
Hagerty RD et al. (2000) Cellular proliferation and macrophage populations associated with implanted expanded polytetrafluoroethylene and polyethyleneterephthalate. J Biomed Mater Res 49: 489–497
Meinhart JG et al. (2001) Clinical autologous in vitro endothelialization of 153 infrainguinal ePTFE grafts. Ann Thorac Surg 71 (5 Suppl): S327–S331
Lamm P et al. (2002) Continuous graft perfusion: optimizing the quality of saphenous vein grafts. Heart Surg Forum 5 (Suppl 4): S355–S361
Lavee J et al. (1989) Complications of saphenous vein harvesting following coronary artery bypass surgery. J Cardiovasc Surg (Torino) 30: 989–991
DeLaria GA et al. (1981) Leg wound complications associated with coronary revascularization. J Thorac Cardiovasc Surg 81: 403–407
Weinberg CB and Bell E (1986) A blood vessel model constructed from collagen and cultured vascular cells. Science 231: 397–400
Isenberg BC et al. (2006) Small-diameter artificial arteries engineered in vitro . Circ Res 98: 25–35
Gong Z et al. (2006) Blood vessels engineered from human cells. Trends Cardiovasc Med 16: 153–156
Swartz DD et al. (2005) Engineering of fibrin-based functional and implantable small-diameter blood vessels. Am J Physiol Heart Circ Physiol 288: H1451–H1460
Girton TS et al. (2000) Mechanisms of stiffening and strengthening in media-equivalents fabricated using glycation. J Biomech Eng 122: 216–223
Hirai J and Matsuda T (1996) Venous reconstruction using hybrid vascular tissue composed of vascular cells and collagen—tissue regeneration process. Cell Transplant 5: 93–105
Seliktar D et al. (2000) Dynamic mechanical conditioning of collagen-gel blood vessel constructs induces remodeling in vitro . Ann Biomed Eng 28: 351–362
Cummings CL et al. (2004) Properties of engineered vascular constructs made from collagen, fibrin, and collagen-fibrin mixtures. Biomat 25: 3699–3706
Grassl ED et al. (2003) A fibrin-based arterial media equivalent. J Biomed Mater Res A 66: 550–561
Hoerstrup SP et al. (2001) Tissue engineering of small caliber vascular grafts. Eur J Cardiothorac Surg 20: 164–169
Shum-Tim D et al. (1999) Tissue engineering of autologous aorta using a new biodegradable polymer. Ann Thorac Surg 68: 2298–2304
Niklason LE et al. (1999) Functional arteries grown in vitro . Science 284: 489–493
Poh M et al. (2005) Blood vessels engineered from human cells. Lancet 365: 2122–2124
Shin'oka T et al. (2001) Transplantation of a tissue-engineered pulmonary artery. N Engl J Med 344: 532–533
Shin'oka T et al. (2005) Midterm clinical result of tissue-engineered vascular autografts seeded with autologous bone marrow cells. J Thorac Cardiovasc Surg 129: 1330–1338
Sparks CH (1969) Autogenous grafts made to order. Ann Thorac Surg 8: 104–113
Sparks CH (1973) Silicone mandril method for growing reinforced autogenous femoro-popliteal artery grafts in situ . Ann Surg 177: 293–300
Campbell JH et al. (1999) Novel vascular graft grown within recipient's own peritoneal cavity. Circ Res 85: 1173–1178
Chue WL et al. (2004) Dog peritoneal and pleural cavities as bioreactors to grow autologous vascular grafts. J Vasc Surg 39: 859–867
L'Heureux N et al. (2006) Human tissue-engineered blood vessels for adult arterial revascularization. Nat Med 12: 361–365
Bouchie A (2002) Tissue engineering firms go under. Nat Biotechnol 20: 1178–1179
TIME Investigators (2001) Trial of invasive versus medical therapy in elderly patients with chronic symptomatic coronary-artery disease (TIME): a randomised trial. Lancet 358: 951–957
Hueb WA et al. (1995) The Medicine, Angioplasty or Surgery Study (MASS): a prospective, randomized trial of medical therapy, balloon angioplasty or bypass surgery for single proximal left anterior descending artery stenoses. J Am Coll Cardiol 26: 1600–1605
Jabbour S et al. (2004) Unanswered ethical and scientific questions for trials of invasive interventions for coronary disease: the case of single vessel disease. Curr Control Trials Cardiovasc Med 5: 2
US Renal Data System (2002) Clinical and economic issues in vascular access for hemodialysis. J Vasc Access 1: 1–29
Illig KA et al. (2003) Financial impact of endoscopic vein harvest for infrainguinal bypass. J Vasc Surg 37: 323–330
Sabik JF III et al. (2005) Comparison of saphenous vein and internal thoracic artery graft patency by coronary system. Ann Thorac Surg 79: 544–551
Manchio JV et al. (2005) Disruption of graft endothelium correlates with early failure after off-pump coronary artery bypass surgery. Ann Thorac Surg 79: 1991–1998
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N L'Heureux is Chief Scientific Officer at Cytograft Tissue Engineering, Inc., San Francisco, CA, USA.
N Dusserre is the Senior Vice President of Manufacturing at Cytograft Tissue Engineering, Inc., San Francisco, CA, USA.
T McAllister is Chief Executive Officer at Cytograft Tissue Engineering, Inc., San Francisco, CA, USA.
The other authors declared they have no competing interests.
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L'Heureux, N., Dusserre, N., Marini, A. et al. Technology Insight: the evolution of tissue-engineered vascular grafts—from research to clinical practice. Nat Rev Cardiol 4, 389–395 (2007). https://doi.org/10.1038/ncpcardio0930
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DOI: https://doi.org/10.1038/ncpcardio0930
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