Future Perspectives in Small-Diameter Vascular Graft Engineering

Abstract

The increased demands of small-diameter vascular grafts (SDVGs) globally has forced the scientific society to explore alternative strategies utilizing the tissue engineering approaches. Cardiovascular disease (CVD) comprises one of the most lethal groups of non-communicable disorders worldwide. It has been estimated that in Europe, the healthcare cost for the administration of CVD is more than 169 billion €. Common manifestations involve the narrowing or occlusion of blood vessels. The replacement of damaged vessels with autologous grafts represents one of the applied therapeutic approaches in CVD. However, significant drawbacks are accompanying the above procedure; therefore, the exploration of alternative vessel sources must be performed. Engineered SDVGs can be produced through the utilization of non-degradable/degradable and naturally derived materials. Decellularized vessels represent also an alternative valuable source for the development of SDVGs. In this review, a great number of SDVG engineering approaches will be highlighted. Importantly, the state-of-the-art methodologies, which are currently employed, will be comprehensively presented. A discussion summarizing the key marks and the future perspectives of SDVG engineering will be included in this review. Taking into consideration the increased number of patients with CVD, SDVG engineering may assist significantly in cardiovascular reconstructive surgery and, therefore, the overall improvement of patients' life.

Keywords: 3D and 4D printing; bypass surgery; cardiovascular disease; decellularization; human umbilical arteries; small-diameter vascular grafts; synthetic materials; thermoresponsive materials; tissue engineering; vascular reconstruction.

Figure 1

Development and implantation of engineered small-diameter vascular grafts (SDVGs). (A) The first approach comprises the production of acellular SDVG derived from polymer materials using the state-of-art bioprinting approach. Then, the manufactured SDVG can be implanted immediately into the patient. In this approach, the patient’s body will serve as a bioreactor for the recellularization of the implanted vascular graft. However, some major disadvantages, including the time period needed for the proper cellularization or the impaired functionality of the produced vascular grafts, maybe existed. (B) The second approach comprises the combination of cellular populations with the polymer derived SDVGs. In this approach, the cells can be isolated from the patient’s tissue biopsy, in vitro expanded, and seeded onto the SDVG. Finally, the engineered SDVG can be implanted back to the patient. The advantage of this approach is the production of compatible SDVGs with the patients, avoiding in this way any potential adverse reactions.

Figure 2

Production of SDVGs with the decellularization approach. Initially, vascular grafts can be obtained either from human cadaveric or animal donor. Then, the obtained SDVG is submitted to decellularization to remove the residual cellular population. The produced acellular vascular graft can be either implanted back to the patient or to submitted in recellularization with the patient’s own cells. The cellular populations can be isolated and expanded from the patient’s tissue biopsy. When cells reached the desired cell number, they can be used for the recellularization of the acellular vascular graft. Finally, the produced cellularized SDVG can be implanted in the patient. The whole procedure can be performed under good manufacturing practice (GMP) conditions.

Figure 3

Fabrication methods for the production of SDVGs. (A) Production of SDVGs with the originally proposed method of L’Heureux et al. In this method, the production of SDVGs was relied on the self-assembly of cell sheets using a tubular mandrel. (B) Production of SDVGs with the electrospinning method. This methodology can produce complicated extracellular matrices (ECMs). In addition, combination with cellular populations can lead to the development of cellularized structures. (C) Production of SDVGs with the bioprinting method. Bioprinting offers the potential for the production of either acellular or cellularized complicated structures. Moreover, when used “smart” materials in the production process, the final product can assembly on the desired structure upon external stimulation (e.g., temperature, pH, humidity, and magnetic field).