3D printing of tissue engineering scaffolds: a focus on vascular regeneration

Abstract

Tissue engineering is an emerging means for resolving the problems of tissue repair and organ replacement in regenerative medicine. Insufficient supply of nutrients and oxygen to cells in large-scale tissues has led to the demand to prepare blood vessels. Scaffold-based tissue engineering approaches are effective methods to form new blood vessel tissues. The demand for blood vessels prompts systematic research on fabrication strategies of vascular scaffolds for tissue engineering. Recent advances in 3D printing have facilitated fabrication of vascular scaffolds, contributing to broad prospects for tissue vascularization. This review presents state of the art on modeling methods, print materials and preparation processes for fabrication of vascular scaffolds, and discusses the advantages and application fields of each method. Specially, significance and importance of scaffold-based tissue engineering for vascular regeneration are emphasized. Print materials and preparation processes are discussed in detail. And a focus is placed on preparation processes based on 3D printing technologies and traditional manufacturing technologies including casting, electrospinning, and Lego-like construction. And related studies are exemplified. Transformation of vascular scaffolds to clinical application is discussed. Also, four trends of 3D printing of tissue engineering vascular scaffolds are presented, including machine learning, near-infrared photopolymerization, 4D printing, and combination of self-assembly and 3D printing-based methods.

Keywords: 3D printing; Modeling methods; Print materials; Tissue engineering; Vascular scaffolds.

Fig. 1

The statistics data from Web of Science for either the topic of 3D printing and tissue engineering and scaffold and artery/arteriole/capillary/vein/venule, or the topic of 3D printing and tissue engineering and scaffold and blood vessel/vascular tissue engineering excluding the topic of artery/arteriole/capillary/vein/venule. Data were retrieved in the past 10 years

Fig. 2

Schematic diagram of organization and hierarchical structures of blood vessels. Blood vessels consist of artery, arteriole, capillary, vein, and venule that span the scale from a few microns to a few millimeters

Fig. 3

Schematic diagram showing the fabrication strategies of scaffold-based tissue engineering by 3D printing for vascular regeneration. A preparation process of vascular scaffolds includes four stages before cell culture: 3D modeling, preparation of print materials, manufacturing processes, and characterization of scaffolds. 3D printing-based manufacturing processes can be used for fabrication of complex vascular scaffolds

Fig. 4

Modeling methods of vascular scaffolds: A Algorithms-based parametric modeling: Ai Modeling by a TPMS algorithm to build models with different volume fractions. Reproduced with permission [65]. Copyright 2014, Elsevier. Aii Modeling by an AI-based evolutionary algorithm to design reconfigurable structures. Reproduced with permission [66]. Copyright 2020, National Academy of Sciences. B Reverse engineering-based modeling to create models of blood vessels: Bi 3D reconstruction by micro-CT scanning. Reproduced with permission [67]. Copyright 2016, Springer Nature. Bii 3D reconstruction by MRI scanning. Reproduced with permission [47]. Copyright 2016, John Wiley and Sons. Biii Modeling by CT scanning and parametric modeling to build complex microstructures. Reproduced with permission [64]. Copyright 2020, Springer Nature

Fig. 5

Crosslinking processes of common hydrogels and preparations of modified SF, functionalized MNPs and silk-graphene hydrogels: A Schematic diagram of a crosslinking process of Gelatin and GelMA. Reproduced with permission [73]. Copyright 2019, American Chemical Society. B Preparation of SF bioink by modification of SF molecules. Reproduced with permission [74]. Copyright 2018, Kim et al. C Preparation of functionalized MNPs with PLGA by co-precipitation and ultrasonication, and preparation of functionalized MNPs by co-precipitation and electro-spraying. Reproduced with permission [76]. Copyright 2017, John Wiley and Sons. D Preparation of silk-graphene hydrogels by electric fields. Reproduced with permission [75]. Copyright 2018, American Chemical Society. E Ionic crosslinking of alginate hydrogels. Reproduced with permission [80]. Copyright 2019, Andrique et al. F Thermal crosslinking of Gelatin and GelMA and photocrosslinking of GelMA. Reproduced with permission [23]. Copyright 2020, Springer Nature

Fig. 6

Extrusion-based 3D printing for scaffold-based vascular tissue engineering: A Preparation of vascular scaffolds with tri-layered hollow channels by an extrusion-based 3D printing device. Reproduced with permission [3]. Copyright 2018, IOP Publishing. B Preparation of vascular scaffolds with built-in microchannels by coaxial nozzle-assisted 3D printing. Reproduced with permission [53]. Copyright 2015, Elsevier. C Preparation of voxelated structures with heterogeneous materials by an extrusion-based multinozzle bioprinter. Reproduced with permission [93]. Copyright 2019, Springer Nature. D Preparation of vascular scaffolds by extrusion-based 3D printing in suspension baths. Reproduced with permission [26]. Copyright 2020, McCormack et al. E Preparation of vascular scaffolds by extrusion-based 3D printing on a stepper motor-driving rotating tubular model. Reproduced with permission [95]. Copyright 2020, Elsevier

Fig. 7

Inkjet 3D printing for scaffold-based vascular tissue engineering: A An inkjet 3D printing device. Reproduced with permission [84]. Copyright 2017, Elsevier. B Inkjet 3D printing processes: Bi Schematic diagram of an inkjet 3D printing process. Reproduced with permission [84]. Copyright 2017, Elsevier. Bii Schematic diagram of a buoyancy-enabled inkjet 3D printing method. Reproduced with permission [98]. Copyright 2018, American Society of Mechanical Engineers ASME. C Schematic diagram of EHD 3D printing devices. Reproduced with permission [99]. Copyright 2020, IOP Publishing. D Sketch of two kinds of EHD 3D printing with ranges of diameter of 500 nm–100 μm. Reproduced with permission [99]. Copyright 2020, IOP Publishing. E An improved EHD 3D printing device with additional electrodes. Reproduced with permission [100]. Copyright 2020, Liashenko et al

Fig. 8

UV-assisted 3D printing for scaffold-based vascular tissue engineering. A Preparation of GelMA scaffolds by stereolithography 3D printing. UV light was directed by a focusing system. Reproduced with permission [107]. Copyright 2018, American Chemical Society. B Preparation of bilayer core–shell structures by DLP printing. Based on a core and shell mask, a light pattern was formed. Reproduced with permission [103]. Copyright 2019, John Wiley and Sons. C Preparation of scaffolds by volumetric additive manufacturing via tomographic reconstruction. Reproduced with permission [105]. Copyright 2020, Loterie et al

Fig. 9

Preparation processes of vascular scaffolds by the integrated technology of casting and 3D printing: A Preparation of vascular scaffolds by the integrated technology of casting and extrusion-based 3D printing. Reproduced with permission [48]. Copyright 2019, IOP Publishing. B Preparation of vascular scaffolds by the integrated technology of casting and EHD 3D printing and FDM 3D printing. Reproduced with permission [136]. Copyright 2020, The Royal Society of Chemistry. C Preparation of cardiac tissues by the integrated technology of UV-assisted 3D printing to prepare a cardiac mold, casting to fill with matrix, and embedded 3D printing to fabricate vascular networks. Reproduced with permission [137]. Copyright 2019, Skylar-Scott et al. D Preparation of vascular scaffolds by corrosion casting with solution perfused into blood vessels. Reproduced with permission [138]. Copyright 2016, Elsevier

Fig. 10

Preparation of vascular scaffolds by the integrated technology of electrospinning and 3D printing: A Preparation of surface structures by the integrated technology of electrospinning and extrusion-based 3D printing to fabricate assembled cell-laden sheets. Reproduced with permission [49]. Copyright 2019, Springer Nature. B Integrated technology of electrospinning and inkjet 3D printing: Bi Preparation of vascular scaffolds by the integrated technology of electrospinning and inkjet 3D printing. Reproduced with permission [62]. Copyright 2018, Elsevier. Bii Preparation of vascular scaffolds by the integrated technology of electrospinning and EHD 3D printing based on a hybrid electrospinning and EHD 3D printing system. Reproduced with permission [144]. Copyright 2017, Emerald Publishing Limited. C Preparation of vascular scaffolds by the integrated technology of electrospinning and stereolithography. Reproduced with permission [145]. Copyright 2017, Mary Ann Liebert, Inc

Fig. 11

Preparation of vascular scaffolds by the integrated technology of Lego-like construction and 3D printing: A Preparation of vascular scaffolds by the integrated technology of Lego-like construction and 3D printing to prepare detachable integral vascular scaffolds with multiple functional modules of flow channel, cell culture, and regulation. Reproduced with permission [50] Copyright 2018, IOP Publishing. B Preparation of scaffolds by the integrated technology of Lego-like construction, 3D printing and conventional casting technology to prepare scaffolds with microchannel structures. Reproduced with permission [151]. Copyright 2017, American Chemical Society

Fig. 12

Estimation of vascular scaffold properties by different integrated technologies and their effects on vascular cell growth and tissue vascularization