Tissue Engineered Vascular Grafts, by Tyler Vlass
Definition
Tissue engineered vascular grafts work as replacement veins and arteries. These grafts can be made from cultured cells or from biomaterials.
Reasons for Vascular Grafts
The main use of vascular grafts is for vascular access during hemodialysis. Hemodialysis (or blood dialysis) is the preferred method used to treat kidney failure and is performed 350,000 times annually [1]. This method uses concentration gradients and a semipermeable membrane to remove waste from the blood. There are three methods to hook up to blood flow in the body to perform hemodialysis. The first method is an arteriovenous fistula, which involves attaching an artery to a vein to increase blood flow to an area, most commonly the arm, then attaching a needle to this vein to extract contaminated blood and put back clean blood. Fistulas usually last the longest out of the three choices and are associated with the least negative side effects. A fistula is not always possible to make depending on size and health of the vasculature. The second method is a venous catheter. This is a temporary fix where a tube is inserted into one of the body’s larger veins, either the neck or leg near the groin. These devices often clog, become infected, or cause the veins in which they are placed to become narrow. The final method is an arteriovenous graft, which is similar to a fistula except that it uses some sort of tubing to indirectly connect an artery to a vein. This artificial vein can be punctured with a needle repeatedly for hemodialysis treatment. These grafts require less preparation time before use than the fistulas, but are more prone to infection and clogging and do not last quite as long [2].
Vascular grafts are also commonly used for vascular bypass in patients with cardiovascular disease when the patient has no suitable counterparts to take elsewhere from their body due to either disease or having previously used other vasculature. The most widely harvested vasculature is taken from the greater saphenous vein in the leg [3].
History
-1940 – Dr. Willem Kolff filled sausage casings with blood and incubated in a saltwater bath as the first form of dialysis for kidney failure [4]
-1943 – Dr. Willem Kolff invents first dialysis machine [4]
-1960 – Scribner Shunt used to connect arteries to veins to allow for ease of connection to dialysis machines [5]
-1970 – Artegraft’s vascular graft approved by the FDA [6]
-1986 –Weinberg and Bell produced cell seeded collagen tubes trying to create novel blood vessels in vivo[7]
Current Fixes
Currently, when autologous grafts cannot be utilized, other grafts can come from animals (xenografts), cadavers (allografts), or made from synthetic materials, such as tubes of polytetrafluoroethylene (PTFE). The xenografts and allografts are susceptible to rupturing (aneurism), hardening (calcification), and blockage (thrombosis), which can result in harm to the patient. The biomaterials are also prone to thrombosis and changing size of the opening (both increasing and decreasing) due to blood flow pressure and growth on the inside of the tube, respectively [3].
Current Tissue Engineered Vascular Grafts
Current tissue engineered vascular grafts are made patient specific and can take 6-9 months to make. These grafts are formed by seeding autologous bone marrow cells onto a polymer or by expanding fibroblasts and endothelial cells in culture. These cell sheets are then rolled around stainless steel into a tube structure of varying diameters. The inner cell layer of the tube structure is dehydrated and seeded with more endothelial cells from the patient. This procedure can cost upwards of $15,000 so alternative methods are being explored [3].
Companies
There are many companies that utilize different styles of vascular grafts. Some notable companies are:
Artegraft – first company to have a vascular graft approved by the FDA (1970) [6]
Cytograft – tissue engineered blood vessels from autologous fibroblast sheets rolled into tubes (LifeLine) [8].
Bionova - biosynthetic vascular patch goes around the vascular wound (Omniflow II) [9]
Latest Research
Biodegradable scaffolds seeded with bone marrow mononuclear cells form into new blood vessels in about 6 months in mice via an inflammatory response. This starts with the seeded bone marrow cells releasing a chemoattractant to initiate the migration of monocytes to the scaffold. These monocytes release cytokines that attract endothelial and smooth muscle cells that completely replace the degraded scaffold [10].
Polyglycolic acid (PGA) tubular scaffolds seeded with smooth muscle cells from a cadaver. The PGA scaffold degrades and is replaced by native extracellular matrix (ECM) proteins, such as collagen I and III, fibronectin, and vitronectin. The cells are exposed to continual, cyclic radial strain in a bioreactor. When the scaffold has degraded significantly, cells are removed from the secreted ECM structure so that it is non-immunogenic. These vascular grafts can be made from any bank of cells and can be used in any person. These engineered grafts can also be stored in phosphate buffers saline (PBS) at 4 degrees celsuis for extended periods of time. These grafts can be made at the same diameter 6-7 mm and smaller diameters 3-4 mm than can be made from rolling up cell sheets. In this study, the smaller diameter vessels were seeded with additional endothelial cells to help prevent thrombosis, though further research is needed to prove if this additional seeding is actually necessary. These novel vasculature can also withstand the necessary forces generated in the human body [3].
References
[1] McAllister, Todd. "First Human Use of an Allogeneic Tissue Engineered Vascular Graft." American Heart Association, 27 June 2011. Web. 13 Mar. 2012. <http://my.americanheart.org/idc/groups/ahamah-public/@wcm/@sop/@scon/documents/downloadable/ucm_428738.pdf>.
[2] "Vascular Access for Hemodialysis." National Kidney & Urologic DiseasesInformation Clearinghouse (NKUDIC). US Department of Health and Human Services. Web. 13 Mar. 2012. <http://kidney.niddk.nih.gov/kudiseases/pubs/vascularaccess/>.
[3] Dahl, Shannon L. "Readily Available Tissue-Engineered Vascular Grafts." Science Translational Medicine 3.68 (2011). PubMed. Web. 13 Mar. 2012. <http://stm.sciencemag.org.silk.library.umass.edu/content/3/68/68ra9.full>.
[4] Blakeslee, Sandra. "Willem Kolff, Doctor Who Invented Kidney and Heart Machines, Dies at 97." The New York Times, 12 Feb. 2009. Web. 13 Mar. 2012. <http://www.nytimes.com/2009/02/13/health/13kolff.html?pagewanted=all>.
[5] "Pioneers in Kidney Dialysis: From the Scribner Shunt and the Mini-II to the "One-Button Machine"" Pathbreakers. University of Washington, 1996. Web. 13 Mar. 2012. <http://www.washington.edu/research/pathbreakers/1960c.html>.
[6] "History." Bovine Carotid Artery Graft. Artegraft, 2012. Web. 13 Mar. 2012. <http://www.artegraft.com/About-Us/History>.
[7] L'Heureux, Nicholas. "Technology Insight: The Evolution of Tissue-Engineered Vascular Grafts: History of Tissue-engineered Vessels." Nat Clin Pract Cardiovasc Med 4.7 (2007): 389-95. Medscape. Web. 13 Mar. 2012. <http://www.medscape.com/viewarticle/559495_2>.
[8] "Tissue Engineered Blood Vessel (TEBV)." Cytograft. 2009. Web. 13 Mar. 2012. <http://www.cytograft.com/tebv.html>.
[9] "Omniflow II for Vascular Repair." Bionova. Storm Worldwide, 2011. Web. 13 Mar. 2012. <http://www.bionova.com.au/bionova-products/714-2/>.
[10] Roh, Jason D. “Tissue-Engineered Vascular Grafts Transform into mature Blood Vessels via an Inflammation-mediated Process of Vascular Remodeling.” PubMed Central. 9 Mar. 2010. <http://www-ncbi-nlm-nih-gov.silk.library.umass.edu/pmc/articles/PMC2842056/?tool=pubmed>.
