Page 418 - IJB-9-4

International Journal of Bioprinting 3D bioprinting of artificial blood vessel

treatment for cardiovascular disease, through which categories: (i) Adding chemical cross-linking agents or using
blood grafts are used to bypass the blockage, and about various chemical reactions to form irreversible covalent
450,000 patients undergo bypass surgery in the United bonding between polymer chains and (ii) using physical
States alone in a year . Organ transplantation is one of cross-linking by H bond and electrostatic attraction, which
[2]
the most important research topics in the 21 century. results in hydrogels with weaker mechanical properties but
st
Despite the improved quality of transplantation and the better biocompatibility [19-21] .
increased survival rate in recent decades, organ shortage is Although no clinical cases of bioprinting of vessels or
still the biggest challenge remaining to be overcome. Tissue vascular structures have been reported, progress in this
engineering was proposed by Joseph P. Vacanti in 1980 who regard has been noted in several animal experiments.
put forward some theoretical basis about artificial organs.
For example, artificial blood vessels prepared by poly(L-
The human vascular system is a complex network lactide-co-caprolactone)-heparin/silk gel were implanted
of blood vessels of various sizes, and the blood vessel is into the carotid artery of New Zealand white rabbits in
constituted by vascular endothelial cells (EC, which form 2020. It was found that the lumen could form a continuous
the intima), vascular smooth muscle cells (SMC, which endodermis 8 months after surgery . Figure 1 shows the
[22]
form the tunica), and fibroblasts [3-5] . The extracellular papers in the field over the past 20 years and the patent
[23]
matrix (ECM) is used as the supporting structure and application status in the past 10 years with data derived
filling material . At present, commercially available from the database of the Patent Office. In this review, the
[6]
artificial implants are made from polymers called expanded necessary properties of artificial blood vessels, the cross-
ePTFE (Gore-Tex) or PET (Dacron), both of which can link method, and the type of hydrogel were discussed to
be prepared into various large-diameter (>6 mm) blood evaluate the possible candidate materials in 3D bioprinting
vessels for storage [7,8] . However, the polymer vessels are area of the artificial blood vessel.
hard, rough, and highly hydrophobic, resulting in poor
biocompatibility and activation of the blood coagulation 2. Performance requirement of hydrogel
cascade; therefore, the polymer is not suitable for small-
diameter artificial vessels [9,10] . 2.1. Physical performance requirements
From the perspective of bionics, three-dimensional The ultimate aim of the artificial blood vessel is to mimic
(3D) printing is the most ideal method to obtain artificial the structure and function of human blood vessels. Based
blood vessels with different functions by forming the three on the “Cardiovascular implants and extracorporeal
cells according to their distribution in natural blood [11,12] . systems – vascular grafts and vascular patches – in vitro
The conventional 3D bioprinting is based on the additive systems tubular vascular grafts and vascular patches (ISO
manufacturing, which adopts layer-by-layer stacking of 7198: 2016),” simulating the mechanical properties of the
special print and bioink to combine organs cells . The core human internal mammary artery is the main purpose
[13]
[24]
issue of 3D printing is to choose the suitable and functional of artificial blood vessel . The theoretical and actual
bioink to load the cells at designated locations . The bioinks burst strength of the natural blood vessel are 3775 and
[14]
[25]
should have better biocompatibility, structural stability, and 3099 mmHg, respectively . The systolic blood pressure of
enough mechanical and rheological properties, especially the hypertensive patient can reach 180 mmHg, so the artificial
ability to allow cell adhesion, proliferation, and diffusion . blood vessel made with the polymer should have a rupture
[15]
The hydrogels contain a large number of water and porous pressure of 1000 mmHg with natural tissue compliance of
[26]
microstructures, which provide the nutrient substances to 10–20%/100 mmHg and tensile strength of >1 MPa . The
cells . Besides, due to their mechanical properties and the properties of the hydrogel and the artificial blood vessels are
[16]
ability to change their physical state between liquid and solid discussed in this subsection to present the basic standard
[27]
using simple methods, hydrogels are regarded an important for guiding the perpetration process . Besides, the tensile
bioink for 3D printing. The prime candidate hydrogels can strength of the natural blood vessel ranges from 0.2 – 0.6
be divided into synthetic polymers and natural polymers . MPa to 2 – 6 MPa. It is important for the artificial vessels to
[17]
[28]
The synthetic polymers mainly contain Pluronic F-127 have similar mechanical properties . The artificial blood
and polyethylene glycol (PEG), while the natural polymers vessel with a diameter of 18–24 mm can be used for the
comprise alginate, fibrous protein, hyaluronic acid (HA), replacement of artificial blood vessel in the thoracic aorta,
and collagen . Nevertheless, the hydrogel is too weak to and the artificial blood vessel with a diameter of 6–10 mm
[18]
undergo surgical procedures and high pulse pressure of can be used for the diversion of artificial blood vessel in
the blood pressure. To improve the properties, a suitable the arteries of extremities and neck. The main mechanical
method for cross-linking hydrogel has to be chosen. The properties of the natural blood vessel and artificial blood
principal cross-linking methods can be divided into two vessel are listed in Table 1.

Volume 9 Issue 4 (2023) 410 https://doi.org/10.18063/ijb.740