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.
Highlights
Vascular diseases have recently become an important threat to human health and, at present, are mainly treated with vascular grafts
It is easy to operate and can be applied flexibly to hierarchical structures [25]. It can even be used for simple branching structures [26]. The limitations of this approach are that the matrix material and vascular channels cannot be formed simultaneously and that it is difficult to control the accurate distribution of the cells in thick tissues
To address the vascularization issue, we developed a novel strategy that employs biomaterials with high biocompatibility and a custom-built 3D bioprinting system to fabricate two types of blood vessels with highly ordered arrangements: blood vessels with a prevascularized cell-layer of endothelial cells in thick tissues and small-diameter blood vessels with a tailored three-layer structure
Summary
Vascular diseases have recently become an important threat to human health and, at present, are mainly treated with vascular grafts. It can even be used for simple branching structures [26] The limitations of this approach are that the matrix material and vascular channels cannot be formed simultaneously and that it is difficult to control the accurate distribution of the cells in thick tissues. Using a rotary printing method, Gao et al bioprinted vessel-like structures with multilevel fluidic channels, which have potential applications in organ-on-chip devices [28]. The limitation of this method is that it does not accurately imitate the three-layer spatial characteristics of blood vessels in vitro
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