Tissue Engineering Vascular Grafts

Vascular grafts are commonly used on damaged or diseased blood vessels when there is a need to redirect blood flow by replacing the vessel [1]. Autologous arteries and veins are seen as the gold standard for vascular grafting; however, a few limitations are associated with this technique, including limited availability, poor quality of the vessels, and possibility of infections [2].


Tissue-engineered vascular grafts (TEVGs) have emerged as a new approach for substituting regular vascular grafts used in conventional treatments. A TEVG must possess specific characteristics, such as matched mechanical properties, blood compatibility, endothelialization capability, and biodegradability. Several studies have already shown that tissue engineered vascular grafts have true potential for clinical applications, as they remain functional in vivo for substantial periods of time [3, 4].


The fabrication of TEVGs can be performed through various techniques, including electrospinning, phase inversion, solvent casting/salt leaching, and freeze-drying. However, these techniques suffer from poor control over the three-dimensional structures’ internal structure, porosity and overall geometry. 3D printing is an effective and precise technique to generate tubular structures with controlled dimensions, pore size and with better reproducibility [5]. The essential advantage of this technology is the potential to produce customized tissue implants to replace damaged parts of the human body [6].


Spadaccio et al. (2016) fabricated a vascular graft consisting of a 3D bioprinted PCL armor with a heparin-releasing PLLA electrospun scaffold. The authors tested in vivo the effectiveness of the vascular graft on releasing heparin when implanted in an aortic vascular reconstruction model in rabbits. The scaffold was functionalized with heparin to allow the attraction and concentration of soluble angiogenic growth factors released in the bloodstream during a vascular injury. The PCL/PLLA graft showed an excellent patency rate and structural integrity. Moreover, the scaffold was adequately populated by endogenous cells, not showing signs of thrombosis or structural failure with no need for antiplatelet therapy [7].



Figure 1: A) Schematic diagram of the experimental procedure. B) Intraoperative photograph showing the PLLA armored scaffold implanted and the infrarenal aorta segment’s ligature between the two anastomoses [7].



The use of 3D bioprinting enables the fabrication of complex structures in a precise way. A branched vascular system was 3D bioprinted with adipose-derived stem cells and cultivated in pulsatile culture. Biodegradable polymers - such as gelatin, alginate, fibrinogen, and chitosan - were used as support scaffolds, while stem cells were engaged to differentiate into different cell types. The generation of vertical channels was enabled by the layer-by-layer assembly of hydrogel mixtures, combining the gelling behavior of gelatin and cross-linking of the additional biopolymers. This proof-of-concept study shows that combining biodegradable polymers and stem cells with bioprinting techniques can provide enormous opportunities for the whole field of tissue engineering of vascular grafts [8, 9].



Figure 2: Layer-by-layer deposition: fabrication process of 3D bioprinted vascular constructs [9].


REFERENCES

1. Fontana, K. & Mutus, B. Nitric Oxide-Donating Devices for Topical Applications. Nitric Oxide Donors 55–74 (2017) doi:10.1016/b978-0-12-809275-0.00003-x.

2. Chircov, C. Tissue engineered vascular grafts. Biomater Tissue Eng Bull 5, 110–118 (2018).

3. Ratcliffe, A. Tissue engineering of vascular grafts. Matrix Biology vol. 19 353–357 (2000).

4. Wu, J. et al. Tissue-engineered Vascular Grafts: Balance of the Four Major Requirements. Colloid and Interface Science Communications vol. 23 34–44 (2018).

5. Elomaa, L. & Yang, Y. P. Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs. Tissue Eng. Part B Rev. 23, 436–450 (2017).

6. Derby, B. Printing and prototyping of tissues and scaffolds. Science 338, 921–926 (2012).

7. Spadaccio, C. et al. Preliminary In Vivo Evaluation of a Hybrid Armored Vascular Graft Combining Electrospinning and Additive Manufacturing Techniques. Drug Target Insights 10, 1–7 (2016).

8. Hoch, E., Tovar, G. E. M. & Borchers, K. Bioprinting of artificial blood vessels: current approaches towards a demanding goal. European Journal of Cardio-Thoracic Surgery vol. 46 767–778 (2014).

9. Lei, M. & Wang, X. Biodegradable Polymers and Stem Cells for Bioprinting. Molecules 21, (2016).


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