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Direct 3D bioprinting of perfusable vascular constructs using a blend bioink
Open accessAbstract
Despite the significant technological advancement in tissue engineering, challenges still exist towards the development of complex and fully functional tissue constructs that mimic their natural counterparts. To address these challenges, bioprinting has emerged as an enabling technology to create highly organized three-dimensional (3D) vascular networks within engineered tissue constructs to promote the transport of oxygen, nutrients, and waste products, which can hardly be realized using conventional microfabrication techniques. Here, we report the development of a versatile 3D bioprinting strategy that employs biomimetic biomaterials and an advanced extrusion system to deposit perfusable vascular structures with highly ordered arrangements in a single-step process. In particular, a specially designed cell-responsive bioink consisting of gelatin methacryloyl (GelMA), sodium alginate, and 4-arm poly(ethylene glycol)-tetra-acrylate (PEGTA) was used in combination with a multilayered coaxial extrusion system to achieve direct 3D bioprinting. This blend bioink could be first ionically crosslinked by calcium ions followed by covalent photocrosslinking of GelMA and PEGTA to form stable constructs. The rheological properties of the bioink and the mechanical strengths of the resulting constructs were tuned by the introduction of PEGTA, which facilitated the precise deposition of complex multilayered 3D perfusable hollow tubes. This blend bioink also displayed favorable biological characteristics that supported the spreading and proliferation of encapsulated endothelial and stem cells in the bioprinted constructs, leading to the formation of biologically relevant, highly organized, perfusable vessels. These characteristics make this novel 3D bioprinting technique superior to conventional microfabrication or sacrificial templating approaches for fabrication of the perfusable vasculature. We envision that our advanced bioprinting technology and bioink formulation may also have significant potentials in engineering large-scale vascularized tissue constructs towards applications in organ transplantation and repair.
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“In this context, the fast development of new fabrication techniques, such as 3D bioprinting, has led to a general decline in the cost and the specialized work involved in fabricating these chips [65 -67].”
From 3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions (2021) · cites this paper as [65]
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“To this end, considerable efforts were made in developing hydrogel-based inks or printing techniques to enhance 3D stability and shape fidelity, such as printing multimaterial inks with combined nozzle system24, 25, photo-crosslinkable hydrogels17, 26, 27, adding viscosifiers28–30, or printing in sacrificial supporting materials31–33.”
From Fibre-infused gel scaffolds guide cardiomyocyte alignment in 3D-printed ventricles (2023) · cites this paper as [24]
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Metadata
- Authors
- Jia, W., Gungor-Ozkerim, P. S., Zhang, Y. S., Yue, K., Zhu, K., Liu, W., Pi, Q., Byambaa, B., Dokmeci, M. R., Shin, S. R., & Khademhosseini, A.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Zhang, Yu Shrike
- Shin, Su Ryon
- Khademhosseini, Ali
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 106
- Pages
- 58-68
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC5300870
- OpenAlex
- W2502401296
- Cited by
- 922
- References
- 67
- Citations by year
- 2026: 37 · 2025: 59 · 2024: 86 · 2023: 97 · 2022: 113 · 2021: 132 · 2020: 121 · 2019: 110 · 2018: 94 · 2017: 68 · 2016: 4
- FWCI
- 44.28
- Type
- journal article
- Language
- en
- Update notices
- erratum (2025-11-01)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biomaterials (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (1K99CA201603-01A1)
- National Institutes of Health (HL099073, EB02597, AR057837, HL092836)
- Natural Sciences and Engineering Research Council of Canada
- National Science Foundation (DMR0847287)
- Türkiye Bilimsel ve Teknolojik Araştırma Kurumu (B.14.2.TBT.0.06.01-219-115543)
- Office of Naval Research
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- 3D bioprinting, perfusable vascular networks, gelatin methacryloyl, sodium alginate, coaxial extrusion, calcium crosslinking, photocrosslinking, endothelial cells, stem cells, vascularized tissue engineering, mechanical strength
- MeSH terms
- Blood Vessels, Cells, Cultured, Equipment Design, Humans, Ink, Organ Culture Techniques, Perfusion, Neovascularization, Physiologic, Bioreactors, Bioartificial Organs, Tissue Engineering, Endothelial Cells, Tissue Scaffolds, Batch Cell Culture Techniques, Printing, Three-Dimensional
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