Challenges and advances in materials and fabrication technologies of small-diameter vascular grafts

(2023) 27:58 Li et al. Biomaterials Research https://doi.org/10.1186/s40824-023-00399-2 Biomaterials Research Open Access REVIEW Challenges and advances in materials and fabrication technologies of small‑diameter vascular grafts Mei‑Xian Li1,2,3†, Qian‑Qi Wei4†, Hui‑Lin Mo2, Yu Ren1,2, Wei Zhang1,2*, Huan‑Jun Lu5* and Yoon Ki Joung3,6*    Abstract The arterial occlusive disease is one of the leading causes of cardiovascular diseases, often requiring revascularization. Lack of suitable small-diameter vascular grafts (SDVGs), infection, thrombosis, and intimal hyperplasia associated with synthetic vascular grafts lead to a low success rate of SDVGs (< 6 mm) transplantation in the clinical treatment of cardiovascular diseases. The development of fabrication technology along with vascular tissue engineering and regenerative medicine technology allows biological tissue-engineered vascular grafts to become living grafts, which can integrate, remodel, and repair the host vessels as well as respond to the surrounding mechanical and biochemical stimuli. Hence, they potentially alleviate the shortage of existing vascular grafts. This paper evaluates the current advanced fabrication technologies for SDVGs, including electrospinning, molding, 3D printing, decellularization, and so on. Various characteristics of synthetic polymers and surface modification methods are also introduced. In addition, it also provides interdisciplinary insights into the future of small-diameter prostheses and discusses vital factors and perspectives for developing such prostheses in clinical applications. We propose that the performance of SDVGs can be improved by integrating various technologies in the near future. Highlights • The commonly used synthetic polymers for vascular grafts are reviewed. • Various methods for surface modification of artificial vascular grafts are summarized. • Latest fabrication techniques for small-diameter vascular grafts and their mechanical and biological properties are systematically summarized. • Current state and future perspective of small-diameter vascular grafts are suggested. Keywords Small-diameter vascular grafts, Surface modification, Cardiovascular diseases, Biomimetics, Tissue engineering † Mei-Xian Li and Qian-Qi Wei contributed equally to this work. *Correspondence: Wei Zhang Huan‑Jun Lu Yoon Ki Joung Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Li et al. Biomaterials Research (2023) 27:58 Page 2 of 22 Graphical Abstract Decellularization Native blood vessels Decellularization Decellularized vascular graft Synthetic polymers for small-diameter vascular grafts Outer annular mold Smooth muscle cell Polymer nanosheet Endothelial cells Coculture of cells Coculture of cells Introduction Cardiovascular diseases have one of the highest morbidities and mortality rates in the world, with an estimated 12.1 million to 18.6 million deaths in the past 30 years [1]. The most common cardiovascular diseases include coronary artery diseases, deep vein thrombosis, and myocardial infarction, usually associated with stenosis and embolism of blood vessels [2–4]. Bypass of grafting using autologous blood vessels, allogenic blood vessels, or artificial blood vessels is one of the most preferred treatments for cardiovascular diseases. The most optimal treatment among them is autologous blood Li et al. Biomaterials Research (2023) 27:58 vessels due to their adequate size and good biocompatibility for long-term patency. However, insufficient supply and trauma of the donor site limit its clinical application. In addition, the grafts of allogenic blood vessels are associated with potent immune responses, leading to the rejection of a graft. Therefore, artificial blood vessels might potentially replace or bypass diseased blood vessels. It is convenient to prepare an artificial vascular graft with a suitable diameter and length. The ideal vascular grafts should meet the following requirements: biocompatibility, mechanical properties, permeability, and anti-thrombosis [5, 6]. A vascular graft should be histo-compatible to resist immune responses and rejection. It must also have satisfactory mechanical properties to retain its integrity and to withstand physiological pressures. Furthermore, the microstructure should be conducive to nutrient exchange, elimination of metabolic products, and cell growth, allowing endothelial cells to attach, proliferate, and form a endothelial layer with tight junction, capable of resisting thrombosis. Nowadays, artificial vascular grafts for larger size diameters (> 6 mm) are used in the global vascular grafts market. In contrast, there is still no successful clinical trial for SDVGs (< 6 mm) which are in great demand for the treatment of various arterial complications such as coronary artery disease and pediatric congenital cardiovascular defects. The Page 3 of 22 main reason is the intimal hyperplasia at the anastomotic site caused by compliance mismatch between SDVGs and native vessels as well as thrombus formation on the synthetic surface of SDVGs, resulting in low patency after implantation [7–9]. To overcome these limitations, various innovative approaches, including ideas such as their structures, surface modifications, and mechanical and biological requirements, are being adopted to mimic native vessels for the long-term patency of SDVGs [10–12]. Native blood vessels have a complex structure with three distinct layers, the inner layer (tunica intima), the middle layer (tunica media), and the outer layer (tunica adventitia), which significantly affects the mechanical and biological properties (Fig. 1) [13]. The inner layer, known as the endothelium, is the thinnest in the structures of a blood vessel, which acts as a barrier controlling the passage of biologically active substances and selectively penetrates fluids, ions, molecu (...truncated)