Three-dimensional bioprinting of artificial blood vessel: Process, bioinks, and challenges

Ya-Chen Hou; Xiaolin Cui; Zhen Qin; Chang Su; Ge Zhang; Jun-Nan Tang; Jing-An Li; Jin-Ying Zhang

doi:10.18063/ijb.740

Article · 2023 Paper GEO V2

Three-dimensional bioprinting of artificial blood vessel: Process, bioinks, and challenges

International Journal of Bioprinting

Full Authors

Ya-Chen Hou
Xiaolin Cui
Zhen Qin
Chang Su
Ge Zhang
Jun-Nan Tang
Jing-An Li
Jin-Ying Zhang

DOI / publisher Google Scholar search Cite

Official Abstract

The coronary artery bypass grafting is a main treatment for restoring the blood supply to the ischemic site by bypassing the narrow part, thereby improving the heart function of the patients. Autologous blood vessels are preferred in coronary artery bypass grafting, but their availability is often limited by due to the underlying disease. Thus, tissue-engineered vascular grafts that are devoid of thrombosis and have mechanical properties comparable to those of natural vessels are urgently required for clinical applications. Most of the commercially available artificial implants are made from polymers, which are prone to thrombosis and restenosis. The biomimetic artificial blood vessel containing vascular tissue cells is the most ideal implant material. Due to its precision control ability, three-dimensional (3D) bioprinting is a promising method to prepare biomimetic system. In the 3D bioprinting process, the bioink is at the core state for building the topological structure and keeping the cell viable. Therefore, in this review, the basic properties and viable materials of the bioink are discussed, and the research of natural polymers in bioink, including decellularized extracellular matrix, hyaluronic acid, and collagen, is emphasized. Besides, the advantages of alginate and Pluronic F127, which are the mainstream sacrificial material during the preparation of artificial vascular graft, are also reviewed. Finally, an overview of the applications in the field of artificial blood vessel is also presented.

Text reproduced verbatim from PMC (source); DOI; CC-BY-NC-4.0.

Research Question

How should bioink composition, rheology, crosslinking and printing strategy be matched to the structural and biological requirements of tissue-engineered vascular constructs, and what limits their clinical translation?

Author Evidence Summary

This review organizes the engineering choices involved in printing vascular constructs. It explains why preserving a lumen and tissue geometry is insufficient without cell compatibility, nutrient transport, mechanical support and a functional endothelial interface. The discussion distinguishes supportive materials from sacrificial templates, examines natural and synthetic hydrogel options, and compares extrusion, jetting, vat polymerization and embedded printing approaches. Examples such as FRESH illustrate how a removable support bath can preserve soft hydrogel structures during fabrication. Those quantitative examples are findings from cited primary experiments, not measurements generated by this review. The synthesis identifies trade-offs between printability, strength and cell viability and discusses maturation, sterilization, manufacturing and regulatory barriers. It does not demonstrate clinical graft effectiveness or identify a universally superior bioink.

Cite this paper

Plain citation

Ya-Chen Hou, Xiaolin Cui, Zhen Qin, Chang Su, Ge Zhang, Jun-Nan Tang, Jing-An Li, Jin-Ying Zhang. Three-dimensional bioprinting of artificial blood vessel: Process, bioinks, and challenges. International Journal of Bioprinting. 2023. https://doi.org/10.18063/ijb.740

Author-controlled citation; verify against the publisher version of record.

BibTeX RIS / EndNote CSL JSON DOI

Research & review context

Research fields: Cardiovascular tissue engineering
Vascular biomaterials
Review topics: Bioink design for vascular constructs
Printing processes and translation barriers
Scientific role: Narrative synthesis connecting hydrogel functions, cell compatibility, fabrication methods and clinical-translation constraints.
Evidence position: Secondary engineering and preclinical synthesis; no new clinical cohort, pooled clinical effect or demonstrated graft efficacy.
Related concepts: Support and sacrificial materials
Embedded hydrogel printing
Endothelialization and durability
Possible citation contexts: Background: material and process trade-offs in tissue-engineered vascular graft research.
Methods rationale: choosing supportive bioinks, removable templates and embedded printing, while tracing quantitative examples to original experiments.

Possible literature-review contexts, not evidence of existing citations. Read the findings and Evidence Scope before citing the original article.

Questions & evidence · Evidence limits · Original article & citation downloads

Evidence Base

Vascular bioprinting: bioink functions, fabrication strategies and translational evidence boundaries

A narrative review connects vascular-graft design requirements with supportive and sacrificial bioinks, printing methods and translational constraints. Its examples derive from prior material, cell and animal studies; it reports no new patient cohort or clinical trial.

material functions distinguished: 2: support materials and sacrificial materials
broad crosslinking categories discussed: 2: chemical/covalent and physical interactions
conventional printing families summarized: 3: extrusion, material jetting and vat polymerization
additional embedded-printing strategy: FRESH, discussed separately in Section 4.4
illustrative cited FRESH process: approximately 22 degrees C support bath; release at 37 degrees C; representative alginate filament diameter 199 +/- 41 micrometres

Counting note

These numbers describe the review organization and one cited technical example. They are not a count of trials, included studies, recruited participants, pooled specimens or a clinical cohort. The FRESH filament measurement comes from Hinton et al. 2015, not a new experiment by the review authors. No overall participant n is assigned.

Key Findings

KF1 Vascular construct design requires coordinated cellular and extracellular-matrix functions rather than a hollow tube alone.

Conceptual synthesis of native-vessel organization and graft design requirements

Evidence for KF1
Measure	Value
cellular components highlighted	3: endothelial cells, vascular smooth muscle cells and fibroblasts
supporting environment	extracellular matrix supports cellular organization and tissue function
design scope	endothelial compatibility, patency, mechanical performance and nutrient transport must be considered together; no clinical efficacy estimate is supplied

Source locator: Section 1: Introduction (sec1-1), paragraph describing endothelial cells, smooth muscle cells, fibroblasts and ECM; Sections 2.1-2.3; Table 1

Permalink to KF1

KF2 Bioinks have different structural roles, and supportive and sacrificial functions should be distinguished.

Material selection for constructing vessel walls and creating removable lumen templates

Evidence for KF2
Measure	Value
functional roles	2: support materials and sacrificial materials
supportive examples discussed	modified PEG, hyaluronic-acid systems, collagen/gelatin systems and decellularized extracellular matrix
sacrificial examples discussed	Pluronic F-127 and alginate-based strategies; material roles depend on formulation and process
scope	a material name alone does not determine graft suitability or whether it acts as support or template

Source locator: Section 3: Bioinks for 3D bioprinting (sec1-3); Section 3.1: Support hydrogel; Sections 3.2.1-3.2.3, including Pluronic F-127 (sec3-6), Alginate (sec3-7) and Discussion on the existing hydrogel (sec3-8); Table 2

Permalink to KF2

KF3 Printability and cell compatibility depend on interacting rheological and crosslinking choices.

Narrative synthesis of hydrogel processing requirements; not a universal validated manufacturing specification

Evidence for KF3
Measure	Value
hydrogel properties explicitly considered	4: shear thinning, yield stress, viscosity and molding ability
broad crosslinking classes	2: chemical/covalent crosslinking and physical interactions such as hydrogen bonding or electrostatic attraction
trade-off	viscosity and rapid stabilization can preserve geometry while extrusion stress, light exposure and other processing conditions can harm cells
scope	performance depends on formulation, cell loading and process conditions; no single optimal recipe is established

Source locator: Section 1: Introduction (sec1-1), crosslinking paragraph; Section 2.2: Hydrogel requirements (sec2-2); Section 2.3: Forming requirements (sec2-3); Section 4.1: Material extrusion (sec2-6)

Permalink to KF3

KF4 The review compares conventional printing families and an embedded-support strategy with different constraints.

Methodological comparison of fabrication approaches rather than a controlled head-to-head effectiveness experiment

Evidence for KF4
Measure	Value
conventional families	3: material extrusion, material jetting and vat polymerization
embedded strategy	FRESH is discussed separately as printing within a removable support bath
method-specific limitations	extrusion involves shear and resolution trade-offs; jetting restricts ink viscosity; vat polymerization requires suitable photosensitive materials; FRESH requires rapid and compatible ink gelation
scope	advantages depend on the intended construct and ink; the review does not establish one method as clinically superior

Source locator: Section 4: 3D bioprinting techniques (sec1-5); Sections 4.1-4.4 (sec2-6 through sec2-9); Table 3

Permalink to KF4

KF5 A cited FRESH experiment illustrates how a removable support bath can preserve soft hydrogel geometry.

Illustrative primary technical experiment by Hinton et al. 2015, summarized in the review; parameters are not a universal vascular-graft standard

Evidence for KF5
Measure	Value
support-bath condition	approximately 22 degrees C during printing
release condition	37 degrees C to melt the gelatin support bath
representative alginate filament	199 +/- 41 micrometres diameter
measurement boundary	filament diameter is not vessel-lumen diameter, clinical graft patency, burst pressure or a patient outcome

Source locator: Section 4.4: Freeform reversible embedding of suspended hydrogel (FRESH) (sec2-9), reference 196; Hinton et al., Science Advances 2015, DOI 10.1126/sciadv.1500758, Results paragraphs on support-bath rheology and alginate-filament printing, Figure 2A-B and Materials and Methods: FRESH 3D printing

Permalink to KF5

KF6 The review identifies unresolved steps between printed constructs and clinical vascular grafts.

Translational appraisal as of the 2023 review, informed by cited in vitro and animal examples rather than new clinical outcome data

Evidence for KF6
Measure	Value
evidence level	review of engineering and preclinical demonstrations; no new patient cohort or clinical trial
historical statement	the authors reported no clinical vessel-bioprinting cases in their review context at publication in 2023
barriers discussed	mechanical durability, endothelial function, maturation, reproducible manufacturing, sterilization and safety
time boundary	the historical statement is not an independently updated 2026 claim about every product, trial or regulatory authorization

Source locator: Section 1: Introduction (sec1-1), clinical-translation paragraph; Section 3.2.3: Discussion on the existing hydrogel (sec3-8); Section 5: Conclusion and future perspectives (sec1-6)

Permalink to KF6

Review Design & Evidence Synthesis

Review profile

Study Design: Narrative methodological review of vascular bioprinting materials, process choices and translational challenges; no new clinical recruitment or pooled meta-analysis
Evidence Type: Literature synthesis of biomaterial properties, printing methods, in vitro constructs and selected preclinical vascular-graft examples
Diseases Covered: coronary artery disease and ischemic-heart-disease bypass context, vascular disease requiring graft replacement
Translation Scope: Engineering and preclinical design framework for tissue-engineered vascular constructs; cited technical demonstrations are not evidence of clinical graft efficacy or routine availability

Evidence domains

vascular structure and graft requirements
bioink rheology and cell compatibility
supportive and sacrificial hydrogels
crosslinking and printing methods
preclinical translation and manufacturing barriers

What This Review Adds

Organizes vascular-bioprinting design around interacting material, cellular and process requirements.
Separates supportive bioinks, sacrificial templates and removable support baths, helping explain why different fabrication strategies use the same material differently.
Connects rheology and crosslinking trade-offs with specific printing approaches and translational barriers.
Provides a route to relevant primary technical studies while keeping literature examples distinct from original evidence generated by the review.

Evidence Scope

Supports

A qualitative design framework for comparing vascular-bioprinting materials and processes.
The need to balance geometry, cell compatibility, mechanical behavior, nutrient transport and manufacturing constraints.
The distinction between supportive materials, sacrificial templates and removable support baths.
A source-located FRESH technical example whose specific parameters were cross-checked against the cited primary paper.
A historical account of translational challenges discussed in the 2023 publication.

Does Not Establish

A pooled clinical effect, a patient sample size, a randomized comparison or a meta-analytic estimate.
A systematic search with reproducible eligibility criteria, formal risk-of-bias assessment or comprehensive evidence coverage.
That any described printed construct is a routinely available, clinically effective or regulator-approved vascular graft.
That an illustrative filament dimension or cell-viability result is a clinical graft outcome or universal manufacturing standard.
A universally optimal bioink, crosslinking method or printing technology.
Current legal or regulatory requirements from the review discussion, or an updated 2026 inventory of trials or products.

Limitations

This is a narrative review and does not report a systematic search, formal study-selection flow or pooled effect analysis.
The examples span different materials, cell systems, constructs and animal contexts, so quantitative values are not directly interchangeable.
Illustrative experimental numbers come from cited primary studies and are not original measurements generated by the review.
No patient cohort, graft-level clinical efficacy comparison or long-term human safety validation was conducted in this publication.
The review reflects literature available at its 2023 publication; it is not a continually updated registry of products, clinical cases or approvals.
Engineering specifications and regulatory discussion require their own current authoritative sources before operational use; this page does not present them as validated current requirements.

When This Study Is Useful to Cite

CU1: What design constraints should be considered in vascular bioprinting?
Qualitative synthesis of cellular, matrix, rheological and mechanical requirements; no clinical effect estimate.
Evidence: KF1, KF3
CU2: How do supportive and sacrificial bioinks differ?
A functional material-design distinction that depends on formulation and process.
Evidence: KF2
CU3: Which printing methods are relevant to vascular constructs?
Narrative method comparison; no controlled ranking of clinical superiority.
Evidence: KF4
CU4: How does a removable support bath enable soft-hydrogel printing?
FRESH mechanism and a source-traced primary technical example; cite Hinton et al. directly for its quantitative experiment.
Evidence: KF5
CU5: What separates vascular-printing demonstrations from clinical graft use?
Historical translational appraisal as of the 2023 review, without a current product/approval inventory.
Evidence: KF6

What This Study Should Not Be Cited to Claim

A pooled clinical effect, a patient sample size, a randomized comparison or a meta-analytic estimate.
A systematic search with reproducible eligibility criteria, formal risk-of-bias assessment or comprehensive evidence coverage.
That any described printed construct is a routinely available, clinically effective or regulator-approved vascular graft.
That an illustrative filament dimension or cell-viability result is a clinical graft outcome or universal manufacturing standard.
A universally optimal bioink, crosslinking method or printing technology.
Current legal or regulatory requirements from the review discussion, or an updated 2026 inventory of trials or products.

Evidence Matrix

Row ID	Component	Context	Finding	Evidence Level	Scope	Source Locator	Evidence refs
evidence-review-1	KF1: Vascular construct design requires coordinated cellular and extracellular-matrix functions rather than a hollow tube alone.	Conceptual synthesis of native-vessel organization and graft design requirements	Vascular construct design requires coordinated cellular and extracellular-matrix functions rather than a hollow tube alone. cellular components highlighted: 3: endothelial cells, vascular smooth muscle cells and fibroblasts; supporting environment: extracellular matrix supports cellular organization and tissue function; design scope: endothelial compatibility, patency, mechanical performance and nutrient transport must be considered together; no clinical efficacy estimate is supplied	Narrative methodological synthesis	Conceptual synthesis of native-vessel organization and graft design requirements	Section 1: Introduction (sec1-1), paragraph describing endothelial cells, smooth muscle cells, fibroblasts and ECM; Sections 2.1-2.3; Table 1	KF1
evidence-review-2	KF2: Bioinks have different structural roles, and supportive and sacrificial functions should be distinguished.	Material selection for constructing vessel walls and creating removable lumen templates	Bioinks have different structural roles, and supportive and sacrificial functions should be distinguished. functional roles: 2: support materials and sacrificial materials; supportive examples discussed: modified PEG, hyaluronic-acid systems, collagen/gelatin systems and decellularized extracellular matrix; sacrificial examples discussed: Pluronic F-127 and alginate-based strategies; material roles depend on formulation and process; scope: a material name alone does not determine graft suitability or whether it acts as support or template	Narrative methodological synthesis	Material selection for constructing vessel walls and creating removable lumen templates	Section 3: Bioinks for 3D bioprinting (sec1-3); Section 3.1: Support hydrogel; Sections 3.2.1-3.2.3, including Pluronic F-127 (sec3-6), Alginate (sec3-7) and Discussion on the existing hydrogel (sec3-8); Table 2	KF2
evidence-review-3	KF3: Printability and cell compatibility depend on interacting rheological and crosslinking choices.	Narrative synthesis of hydrogel processing requirements; not a universal validated manufacturing specification	Printability and cell compatibility depend on interacting rheological and crosslinking choices. hydrogel properties explicitly considered: 4: shear thinning, yield stress, viscosity and molding ability; broad crosslinking classes: 2: chemical/covalent crosslinking and physical interactions such as hydrogen bonding or electrostatic attraction; trade-off: viscosity and rapid stabilization can preserve geometry while extrusion stress, light exposure and other processing conditions can harm cells; scope: performance depends on formulation, cell loading and process conditions; no single optimal recipe is established	Narrative methodological synthesis	Narrative synthesis of hydrogel processing requirements; not a universal validated manufacturing specification	Section 1: Introduction (sec1-1), crosslinking paragraph; Section 2.2: Hydrogel requirements (sec2-2); Section 2.3: Forming requirements (sec2-3); Section 4.1: Material extrusion (sec2-6)	KF3
evidence-review-4	KF4: The review compares conventional printing families and an embedded-support strategy with different constraints.	Methodological comparison of fabrication approaches rather than a controlled head-to-head effectiveness experiment	The review compares conventional printing families and an embedded-support strategy with different constraints. conventional families: 3: material extrusion, material jetting and vat polymerization; embedded strategy: FRESH is discussed separately as printing within a removable support bath; method-specific limitations: extrusion involves shear and resolution trade-offs; jetting restricts ink viscosity; vat polymerization requires suitable photosensitive materials; FRESH requires rapid and compatible ink gelation; scope: advantages depend on the intended construct and ink; the review does not establish one method as clinically superior	Narrative methodological synthesis	Methodological comparison of fabrication approaches rather than a controlled head-to-head effectiveness experiment	Section 4: 3D bioprinting techniques (sec1-5); Sections 4.1-4.4 (sec2-6 through sec2-9); Table 3	KF4
evidence-review-5	KF5: A cited FRESH experiment illustrates how a removable support bath can preserve soft hydrogel geometry.	Illustrative primary technical experiment by Hinton et al. 2015, summarized in the review; parameters are not a universal vascular-graft standard	A cited FRESH experiment illustrates how a removable support bath can preserve soft hydrogel geometry. support-bath condition: approximately 22 degrees C during printing; release condition: 37 degrees C to melt the gelatin support bath; representative alginate filament: 199 +/- 41 micrometres diameter; measurement boundary: filament diameter is not vessel-lumen diameter, clinical graft patency, burst pressure or a patient outcome	Cited primary technical example, independently checked	Illustrative primary technical experiment by Hinton et al. 2015, summarized in the review; parameters are not a universal vascular-graft standard	Section 4.4: Freeform reversible embedding of suspended hydrogel (FRESH) (sec2-9), reference 196; Hinton et al., Science Advances 2015, DOI 10.1126/sciadv.1500758, Results paragraphs on support-bath rheology and alginate-filament printing, Figure 2A-B and Materials and Methods: FRESH 3D printing	KF5
evidence-review-6	KF6: The review identifies unresolved steps between printed constructs and clinical vascular grafts.	Translational appraisal as of the 2023 review, informed by cited in vitro and animal examples rather than new clinical outcome data	The review identifies unresolved steps between printed constructs and clinical vascular grafts. evidence level: review of engineering and preclinical demonstrations; no new patient cohort or clinical trial; historical statement: the authors reported no clinical vessel-bioprinting cases in their review context at publication in 2023; barriers discussed: mechanical durability, endothelial function, maturation, reproducible manufacturing, sterilization and safety; time boundary: the historical statement is not an independently updated 2026 claim about every product, trial or regulatory authorization	Narrative methodological synthesis	Translational appraisal as of the 2023 review, informed by cited in vitro and animal examples rather than new clinical outcome data	Section 1: Introduction (sec1-1), clinical-translation paragraph; Section 3.2.3: Discussion on the existing hydrogel (sec3-8); Section 5: Conclusion and future perspectives (sec1-6)	KF6

Q&A

Is this an original patient study of printed vascular grafts?

No. It is a narrative review of materials, printing processes and translation challenges. It has no newly recruited clinical cohort and no pooled patient-effect estimate.

Evidence: KF6

Why is printing a hollow channel insufficient for a vascular graft?

The review connects vessel geometry with endothelial function, supportive smooth muscle and fibroblast roles, extracellular matrix, mechanical behavior and nutrient transport. A channel alone does not establish patency or clinical durability.

Evidence: KF1

What is the difference between supportive and sacrificial materials?

Supportive materials help form and stabilize the construct. Sacrificial materials create temporary templates that can be removed to leave a lumen. The role depends on formulation and fabrication strategy.

Evidence: KF2

Why does increasing ink viscosity not solve every printing problem?

Higher viscosity can help preserve geometry but may require higher extrusion pressure and increase cell stress. Crosslinking, cell loading and transport also matter, so printability and biological performance must be balanced.

Evidence: KF3

Which fabrication approaches are compared?

The review summarizes extrusion, material jetting and vat polymerization, then discusses FRESH as an embedded-support strategy. Their constraints differ and the review is not a controlled clinical comparison.

Evidence: KF4

What does the 199 +/- 41 micrometre FRESH value describe?

It is the diameter of a representative alginate filament in the cited Hinton et al. technical experiment. It is not a patient outcome, a graft lumen diameter or a measurement newly generated by this review.

Evidence: KF5

Does the review demonstrate clinical benefit or regulatory approval?

No. It describes engineering and preclinical evidence and translation barriers. Its statement about the absence of reported clinical cases is tied to the 2023 review context and is not an updated inventory of every trial or product.

Evidence: KF6

Concepts & Entities

Application

tissue-engineered vascular graftsvascular bioprintingcoronary bypass graft context

Materials

hyaluronic acidcollagengelatin methacryloyldecellularized extracellular matrixalginatePluronic F-127modified polyethylene glycol

Processes

material extrusionmaterial jettingvat polymerizationFRESHsacrificial templatingcrosslinking

Design Constraints

shear thinningyield stresscell compatibilityendothelial functionmechanical durabilitynutrient transport

Related Research

Biodegradable Mg alloy modified with bioactive exosomes for cardiovascular stent application
A cardiovascular-stent biomaterial study involving exosome-modified magnesium alloy; a distinct device/material application that complements the review design discussion without validating bioprinted grafts. · DOI: 10.1016/j.jma.2023.05.007
Modeling Diabetic Cardiomyopathy Using Human Cardiac Organoids: Effects of High Glucose and Lipid Conditions
A human cardiac-organoid model study illustrating another three-dimensional cardiovascular research context; organoid disease modeling and implantable vascular-graft engineering have different endpoints and evidence requirements. · DOI: 10.1016/j.cbi.2025.111421

Publication & Provenance

DOI: https://doi.org/10.18063/ijb.740
Publisher: https://doi.org/10.18063/ijb.740
Doi Url: https://doi.org/10.18063/ijb.740
PubMed: https://pubmed.ncbi.nlm.nih.gov/37323481/
Pmc Url: https://pmc.ncbi.nlm.nih.gov/articles/PMC10261152/
PMCID: PMC10261152
Version Of Record: International Journal of Bioprinting 2023;9(4):740, published 28 April 2023; DOI 10.18063/ijb.740; PubMed publication type Review
License: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0), article-level license in PMC. This evidence summary uses original factual synthesis; no figures or tables are reproduced.
License Url: https://creativecommons.org/licenses/by-nc/4.0/
Author Identity: Ge Zhang is author 5, affiliated with Cardiology at the First Affiliated Hospital of Zhengzhou University and the associated Henan cardiovascular research centers. The same DOI is listed in public ORCID 0000-0002-3116-3246, including work put-code 136257902. The article itself does not supply an ORCID for this author.
Orcid Url: https://orcid.org/0000-0002-3116-3246
Primary Technical Example Url: https://pmc.ncbi.nlm.nih.gov/articles/PMC4646826/
Primary Technical Example: Hinton et al., Three-dimensional printing of complex biological structures by freeform reversible embedding of suspended hydrogels, Science Advances 2015;1:e1500758, DOI 10.1126/sciadv.1500758, review reference 196. The support-bath temperature, release temperature and illustrative filament diameter were independently cross-checked in the primary text.
Supporting Material: No article-level supplementary experimental dataset is required for the claims on this review page; the source is a literature synthesis, with technical examples traced to its references.
Preprint Relation: No linked preprint was identified in the inspected publisher/PMC/Crossref metadata; no new exhaustive literature search was performed.
Evidence Basis: Version-of-record full-text XML, PubMed/Europe PMC author-affiliation and publication-type metadata, Crossref DOI metadata, public ORCID works and the cited primary FRESH paper, checked 15 October 2026.

Author-controlled evidence page for this review. This original synthesis separates cited technical examples from the review's own contribution and does not replace the publisher's version of record.

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