Leveraging printability and biocompatibility in materials for printing implantable vessel scaffolds

Abstract

Vessel scaffolds are crucial for treating cardiovascular diseases (CVDs). It is currently feasible to fabricate vessel scaffolds from a variety of materials using traditional fabrication methods, but the risks of thrombus formation, chronic inflammation, and atherosclerosis associated with these scaffolds have led to significant limitations in the clinical usages. Bioprinting, as an emerging technology, has great potential in constructing implantable vessel scaffolds. During the fabrication of the constructs, the biomaterials used for bioprinting have offered significant contributions for the successful fabrications of the vessel scaffolds. Herein, we review recent advances in biomaterials for bioprinting implantable vessel scaffolds. First, we briefly introduce the requirements for implantable vessel scaffolds and its conventional manufacturing methods. Next, a brief overview of the classic methods for bioprinting vessel scaffolds is presented. Subsequently, we provide an in-depth analysis of the properties of the representative natural, synthetic, composite and hybrid biomaterials that can be used for bioprinting implantable vessel scaffolds. Ultimately, we underscore the necessity of leveraging biocompatibility and printability for biomaterials, and explore the unmet needs and potential applications of these biomaterials in the field of bioprinted implantable vessel scaffolds.

Keywords: Biocompatibility; Biomaterials; Bioprinting; Implantable vessel scaffolds; Printability.

Graphical abstract

Fig. 1

Schematic illustration of biomaterials for bioprinting implantable vessel scaffolds. Utilizing bioprinting to fabricate implantable vessel scaffolds, the biomaterials required are of paramount importance. There are natural biomaterials (e.g., Alginate, Agarose, Gelatin, Silk Fibroin), synthetic biomaterials (e.g., polyethylene glycol (PEG), PCL, PF127) and composites (e.g., GelMA-MeTro, TEMPO-CNFs and PEG-4NB). Fig. 1 also illustrates the formation of composite and hybrid biomaterials through the incorporation of crosslinking principles, such as non-covalent and covalent crosslinking. The fundamental properties of the implantable vessel scaffolds, including biocompatibility and biological activity, mechanical properties and physical properties should also be considered.

Fig. 2

Bioprinting methods for vessel scaffold fabrication and speed comparison of them. A) Schematic showing the different bioprinting methods. i) Extrusion; ii) Inkjet; iii) LIFT; iv) Vat-photopolymerization. Reproduced and adapted with permission [72]. Copyright 2021, John Wiley and Sons. B) Speed comparison of different printing methods. Reproduced and adapted with permission [72]. Copyright 2021, John Wiley and Sons.

Fig. 3

Specific printing methods for implantable vessel scaffolds. A) Advanced extrusion printing methods. i) Coaxial Printing. Reproduced and adapted with permission [35]. Copyright 2017, John Wiley and Sons. ii) FRESH. Reproduced and adapted with permission [36]. Copyright 2020, John Wiley and Sons. iii) Rotary Printing. Reproduced and adapted with permission [33]. Copyright 2020, Elsevier. iv) Multi-nozzle printing. Reproduced and adapted with permission [15]. Copyright 2018, IOP Publishing. B) Drop-on-demand printing. Reproduced and adapted with permission [90]. Copyright 2016, IOP Publishing. C) MAPLE DW, a common form of modified LIFT. Reproduced and adapted with permission [93]. Copyright 2015, IOP Publishing. D) SLA, a method of vat-photopolymerization. Reproduced and adapted with permission [94]. Copyright 2015, Royal Society of Chemistry. E) DLP, a method of vat-photopolymerization. Reproduced and adapted with permission [97]. Copyright 2020, Elsevier.

Fig. 4

Modified alginate in vessel scaffold printing. A) Schematic Illustration of the Fabrication of a Tubular Construct with Layered ECs and SMCs in a Collagen Gel. Reproduced and adapted with permission [105]. Copyright 2008, American Chemical Society. B) Photographs and H&E stained cross-sections of bioprinted tubular structure and fluorescence microscopic image of a cross-section of the cell layer at 6 days after fiber degradation using alginate lyase. Reproduced and adapted with permission [105]. Copyright 2008, American Chemical Society. C) Summary table of the preferable range of alginate samples with high printability (green) based on the three established printability criteria. Reproduced and adapted with permission [79]. Copyright 2014, Elsevier. D) 3D reconstruction and ortho-slices showing a lumenized endothelial tube. Reproduced and adapted with permission [104]. Copyright 2021, American Chemical Society.

Fig. 5

Bioprinted vascular structures with different fiber diameters, spacing and orientation fabricated from Gel-NOR. A) Structural diagrams of layered vessels printed at different angles (30°, 60°, 90°) using modified gelatin polymers. B) Quantification of average vessel junctions density after 7 days of culture. C) Quantification of average vessel length after 7 days of culture. D) Cross-sectional views of the constructs. Reproduced and adapted with permission [98]. Copyright 2021, John Wiley and Sons.

Fig. 6

Vascular channels printed with PF127 as the sacrificial material. A)-B) Multilevel channel structure and a multibranch channel structure printed in dECM with PF127 as the sacrificial material. Reproduced and adapted with permission [86]. Copyright 2018, MDPI. C)-D) Vascular channels printed in GelMA and other substances with PF127 as the sacrificial material. Reproduced and adapted with permission [80]. Copyright 2021, American Chemical Society.

Fig. 7

Composite and hybrid polymers containing gelatin in vessel scaffold printing. A) Micro-CT photographs of the cross section of the bioprinted channel and the cross section of the end point of the attached scaffold. Reproduced and adapted with permission [89]. Copyright 2021, Elsevier. B) Perfusion images of the channel. Reproduced and adapted with permission [89]. Copyright 2021, Elsevier. C) Schematic and cross-sectional fluorescence images of the bioprinted vascularized heart construct. Reproduced and adapted with permission [36]. Copyright 2020, John Wiley and Sons. D) H&E stained images of the vascularized heart constructs on day 7 and day 21 after implantation in rats. Reproduced and adapted with permission [36]. Copyright 2020, John Wiley and Sons. E) Histological sections and cross-sectional images of the vascular constructs at days 3, 24 and 45. Reproduced and adapted with permission [84]. Copyright 2019, Elsevier.

Fig. 8

Arterial and venous catheters printed using alginate and gelatin and their application in vivo and in vitro. A) Schematic of the structure of the native vein and bioprinted venous conduit, and fluorescence microscopy images of HUVSMCs and HUVECs in the printed vein. Reproduced and adapted with permission [82]. Copyright 2022, American Association for the Advancement of Science. B) Schematic diagram of the structure of native artery and bioprinted arterial conduit, and fluorescence microscopy images of HUASMCs in pairs of printed arteries. Reproduced and adapted with permission [82]. Copyright 2022, American Association for the Advancement of Science. C) In vitro attachment and perfusion of bioprinted vascular conduit connected to native vessels via bioglue, and in vivo implantation and perfusion of mouse vena cava with printed vascular conduit. Reproduced and adapted with permission [82]. Copyright 2022, American Association for the Advancement of Science.

Fig. 9

Composite and hybrid polymers containing synthetic polymer in vessel scaffold printing. A) Representative confocal micrographs of F-actin/nuclear staining after 21 days of culture after bioprinting and confocal images of vascular structures after 14 (I) and 21 (II) days of culture. Reproduced and adapted with permission [81]. Copyright 2016, Elsevier. B) Bulk print products of vessel scaffolds and red dye perfusion assays of scaffolds. Reproduced and adapted with permission [33]. Copyright 2020, Elsevier. C) SEM images of vessel scaffolds with different carbon nanotube concentrations (0 %, 0.5 % and 1 %). Reproduced and adapted with permission [33]. Copyright 2020, Elsevier.

Fig. 10

Printability and biocompatibility of biomaterials need to be balanced.

Fig. 11

A) Number of papers on biomaterials used for vessel scaffolds bioprinting, and B) year of earliest appearance of biomaterials. (These data were taken from the pubmed platform and the keywords entered were: bioprint/bio-print + blood vessel/vascular scaffold/graft + name of each biomaterial).