A Novel Strategy for Creating Tissue-Engineered Biomimetic Blood Vessels Using 3D Bioprinting Technology

Abstract

In this work, a novel strategy was developed to fabricate prevascularized cell-layer blood vessels in thick tissues and small-diameter blood vessel substitutes using three-dimensional (3D) bioprinting technology. These thick vascularized tissues were comprised of cells, a decellularized extracellular matrix (dECM), and a vasculature of multilevel sizes and multibranch architectures. Pluronic F127 (PF 127) was used as a sacrificial material for the formation of the vasculature through a multi-nozzle 3D bioprinting system. After printing, Pluronic F127 was removed to obtain multilevel hollow channels for the attachment of human umbilical vein endothelial cells (HUVECs). To reconstruct functional small-diameter blood vessel substitutes, a supporting scaffold (SE1700) with a double-layer circular structure was first bioprinted. Human aortic vascular smooth muscle cells (HA-VSMCs), HUVECs, and human dermal fibroblasts–neonatal (HDF-n) were separately used to form the media, intima, and adventitia through perfusion into the corresponding location of the supporting scaffold. In particular, the dECM was used as the matrix of the small-diameter blood vessel substitutes. After culture in vitro for 48 h, fluorescent images revealed that cells maintained their viability and that the samples maintained structural integrity. In addition, we analyzed the mechanical properties of the printed scaffold and found that its elastic modulus approximated that of the natural aorta. These findings demonstrate the feasibility of fabricating different kinds of vessels to imitate the structure and function of the human vascular system using 3D bioprinting technology.

3D Bioprinting: from Benches to Translational Applications

“…Using Pluronic F127 as sacrificial material they indicated bioprinting of blood vessels with a smallest diameter of 500 µm embedded in a dECM‐based tissue‐like construct containing MDA‐MB‐231 breast cancer cells. After seeding with HUVECs they obtained endothelial‐coated vessels within the construct . Similarly, Lee et al exploited the advantage of the phase‐changing property of gelatin, a highly biocompatible material, as bioink for creation of perfusable vascular channels .…”

Processed Tissue–Derived Extracellular Matrices: Tailored Platforms Empowering Diverse Therapeutic Applications

“…While the physical properties of synthetic polymers are easily controllable, they generally exhibit poor biocompatibility, toxic degradation products, and lack of bioactivity . The utilization of dECM as a bioink for 3D printing of tissue engineered constructs is, therefore, increasingly being employed by numerous research groups . For its printing, the dECM must first be solubilized or “fluidized” to enable its extrusion through the printing apparatus.…”

“…The patterning of vascular network channels is commonly obtained through the preprinting of sacrificial bioink components such as Pluronic F127, upon which the desired tissue‐mimicking biomaterial is cast, followed by the elution of the sacrificial component, leaving behind a hollow conduit . This technique can be used to fabricate thick tissues with multilevel cell‐laden channels of different hydraulic diameters, utilizing porcine cartilage dECM . A sacrificial bioink was also applied to produce artificial blood vessels incorporating endothelial progenitor cells, aortic‐derived dECM, alginate, and a proangiogenic agent enclosed within poly (lactic‐ co ‐glycolic) (PLGA) microparticles, leading to endothelial differentiation and neovascularization in an ischemic nude mouse model ( Figure a,b) .…”

“…The recovery of intact small‐diameter blood vessels through decellularization procedures can be extremely challenging. Nevertheless, the production of cartilage dECM‐based 3D printing of small‐diameter blood vessels with a tailored three‐layer structure could be executed through utilizing supportive scaffolds such as SE 1700—a type of polydimethylsiloxane (PDMS) elastomer (Figure c,d) . Prospective advances in bioprinting technology may realize the development of complex vascular structures consisting of multiple types of dECM materials with distinct properties and crosslinking patterns, providing more effective vascular reconstruction solutions.…”

“…d) A fluorescent image of the blood vessel showing the three types of cells in their respective spatial locations. Reproduced with permission . Copyright 2018, MDPI AG.…”