Considerations in the Development of Small-Diameter Vascular Graft as an Alternative for Bypass and Reconstructive Surgeries: A Review

Abstract

Background-Current design strategies for small diameter vascular grafts (< 6 mm internal diameter; ID) are focused on mimicking native vascular tissue because the commercially available grafts still fail at small diameters, notably due to development of intimal hyperplasia and thrombosis. To overcome these challenges, various design approaches, material selection, and surface modification strategies have been employed to improve the patency of small-diameter grafts. Review-The purpose of this review is to outline various considerations in the development of small-diameter vascular grafts, including material choice, surface modifications to enhance biocompatibility/endothelialization, and mechanical properties of the graft, that are currently being implanted. Additionally, we have taken into account the general vascular physiology, tissue engineering approaches, and collective achievements of the authors in this area. We reviewed both commercially available synthetic grafts (e-PTFE and PET), elastic polymers such as polyurethane and biodegradable and bioresorbable materials. We included naturally occurring materials by focusing on their potential application in the development of future vascular alternatives. Conclusion-Until now, there are few comprehensive reviews regarding considerations in the design of small-diameter vascular grafts in the literature. Here-in, we have discussed in-depth the various strategies employed to generate engineered vascular graft due to their high demand for vascular surgeries. While some TEVG design strategies have shown greater potential in contrast to autologous or synthetic ePTFE conduits, many are still hindered by high production cost which prevents their widespread adoption. Nonetheless, as tissue engineers continue to develop on their strategies and procedures for improved TEVGs, soon, a reliable engineered graft will be available in the market. Hence, we anticipate a viable TEVG with resorbable property, fabricated via electrospinning approach to hold a greater potential that can overcome the challenges observed in both autologous and allogenic grafts. This is because they can be mechanically tuned, incorporated/surface-functionalized with bioactive molecules and mass-manufactured in a reproducible manner. It is also found that most of the success in engineered vascular graft approaching commercialization is for large vessels rather than small-diameter grafts used as cardiovascular bypass grafts. Consequently, the field of vascular engineering is still available for future innovators that can take up the challenge to create a functional arterial substitute.

Tissue-Engineered Carotid Artery Interposition Grafts Demonstrate High Primary Patency and Promote Vascular Tissue Regeneration in the Ovine Model

“…Despite immense efforts to reduce morbidity from atherosclerotic vascular disease [1] which have resulted in a steady decrease in the number of coronary artery bypass grafting procedures worldwide, this treatment modality remains common (82 procedures per 100,000 US adults annually) [2,3]. Vascular bypass implies the use of autologous blood vessel conduits (e.g., saphenous vein or internal mammary artery (IMA)) [4,5] while other types of arterial reconstruction involve biostable tubular scaffolds (e.g., Poly(ethylene terephthalate) (PET), expanded poly(tetrafluoroethylene) (ePTFE), or polyurethane prostheses) [6,7]. Yet, the limited availability of autografts (because of prior surgery, extensive atherosclerosis, or anatomical incompatibility) and high rate of thrombotic occlusion and neointimal hyperplasia in small diameter biostable prostheses limit their use in cardiovascular surgery [8,9].…”

“…To improve the hemocompatibility of this scaffold, here we attached an anticoagulant heparin (Hep) and a vasodilator/antiplatelet drug iloprost (Ilo) to its luminal surface (PHBV/PCL[VEGF-bFGF-SDF] Hep/Ilo ). Biostable ePTFE vascular prostheses, which are frequently used in cardiovascular surgery, were selected as a control group [6,7]. For the proper assessment of the long-term primary patency and ultrastructural features, we used a sheep carotid artery interposition model since ovine arterial anatomy, haemodynamic conditions, and coagulation are similar to humans, while the long neck provides easy surgical access [28][29][30].…”

Selection of different endothelialization modes and different seed cells for tissue-engineered vascular graft

“… *Can be tailored with specific physical properties to suit particular applications *Convenient production *Appropriate mechanical properties *Toxic degradation products and loss of mechanical properties during degradation *Can't accurately mimic the in vivo microenvironment of cells *Poor regeneration of vascular wall and partial calcification [ 19 , 20 , [52] , [53] , [54] ] Natural polymer scaffold Collagen, gelatin, chitosan, etc. *Promote adhesion and proliferation of ECs *Excellent biodegradable and biocompatible properties *Stimulate the colonization of recruited cells Inhibit thrombosis and promote endothelium attachment *May degrade rapidly and poor mechanical strength *Material sourced from an animal could lead to potential disease transmission *Variable quality assurance [ 35 , [55] , [56] , [57] ] Decellularized scaffold Umbilical artery, umbilical vein, animal artery, etc. *Keep the structure and properties of ECM *Extractable from specific tissue of interest *Extremely low immunogenicity *Strong affinity, good biocompatibility *Fast degradation rate of scaffolds *Inability to alter the content and structure of an ECM *Risk of viral transmission from animal tissues *Graft-related thrombosis, infection, and aneurysm *Variable in composition/quality from batch to batch [ 9 , 39 , 58 , 59 ] …”

Harnessing Mechanosensation in Next Generation Cardiovascular Tissue Engineering

“…Summarizing, a functional vascular graft material should have: proper mechanical characteristics, in order to withstand pressure and flow forces; suitable suturability and ease of use; a broad availability in different sizes, a good porosity, reasonable manufacturing cost and long term patency [141]. Additionally, bioartificial vascular grafts could be also functionalized with drugs/miRNAs in order to prevent the mechano-dependent development of cardiovascular pathologies.…”