Hydrogel bioprinted microchannel networks for vascularization of tissue engineering constructs
Open accessAbstract
Vascularization remains a critical challenge in tissue engineering. The development of vascular networks within densely populated and metabolically functional tissues facilitate transport of nutrients and removal of waste products, thus preserving cellular viability over a long period of time. Despite tremendous progress in fabricating complex tissue constructs in the past few years, approaches for controlled vascularization within hydrogel based engineered tissue constructs have remained limited. Here, we report a three dimensional (3D) micromolding technique utilizing bioprinted agarose template fibers to fabricate microchannel networks with various architectural features within photocrosslinkable hydrogel constructs. Using the proposed approach, we were able to successfully embed functional and perfusable microchannels inside methacrylated gelatin (GelMA), star poly(ethylene glycol-co-lactide) acrylate (SPELA), poly(ethylene glycol) dimethacrylate (PEGDMA) and poly(ethylene glycol) diacrylate (PEGDA) hydrogels at different concentrations. In particular, GelMA hydrogels were used as a model to demonstrate the functionality of the fabricated vascular networks in improving mass transport, cellular viability and differentiation within the cell-laden tissue constructs. In addition, successful formation of endothelial monolayers within the fabricated channels was confirmed. Overall, our proposed strategy represents an effective technique for vascularization of hydrogel constructs with useful applications in tissue engineering and organs on a chip.
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Microfabrication enables biomaterials to support long-lasting open EC lumens for perfusion, define capillary networks mimicking native vascular hierarchy, and guide and support EC growth and function.
“Microfabrication enables the use of biomaterials to 1) support long-lasting open EC lumens for perfusion; 2) define sophisticated capillary networks to mimic the hierarchy of native vasculature; 3) guide and support EC growth and maintain their cellular functions [259–263].”
From Cardiovascular disease models: A game changing paradigm in drug discovery and screening (2019) · cites this paper as [263]
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“The sacrificial agarose segments could be eas ily removed from the GelMA matrix by simply pulling of the agarose cords, resulting in a bioprinted GelMA scaffold with internal hollow “vessels” [63].”
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Self-citationBio-inks for 3D bioprinting: recent advances and future prospects
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Engineering an in vitro air-blood barrier by 3D bioprinting
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Bioprinting: From Tissue and Organ Development to in Vitro Models
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3D Bioprinting for Cartilage and Osteochondral Tissue Engineering
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Gelatin-Based Hydrogels for Organ 3D Bioprinting
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State-of-the-Art Review of 3D Bioprinting for Cardiovascular Tissue Engineering
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Developments of 3D Printing Microfluidics and Applications in Chemistry and Biology: a Review
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3D bioprinting for skin tissue engineering: Current status and perspectives
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Engineering Smart Composite Hydrogels for Wearable Disease Monitoring
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Engineering Organoid Vascularization
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3D Printing in Suspension Baths: Keeping the Promises of Bioprinting Afloat
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Functional Biomaterials for Bone Regeneration: A Lesson in Complex Biology
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3D neural tissue models: From spheroids to bioprinting
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3D Bioprinting of Vessel-like Structures with Multilevel Fluidic Channels
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Multiscale bioprinting of vascularized models
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Self-citationDevelopment of a 3D cell printed construct considering angiogenesis for liver tissue engineering
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Biomaterials-based 3D cell printing for next-generation therapeutics and diagnostics
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Review of 3D printable hydrogels and constructs
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Bioprinting the Cancer Microenvironment
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Self-citationOrgans-on-a-Chip Module: A Review from the Development and Applications Perspective
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3D printing of complex GelMA-based scaffolds with nanoclay
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Extrusion bioprinting: Recent progress, challenges, and future opportunities
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Three-Dimensional Bioprinting for Regenerative Dentistry and Craniofacial Tissue Engineering
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Self-citationComplex 3D‐Printed Microchannels within Cell‐Degradable Hydrogels
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3D Bioprinting for Vascularized Tissue Fabrication
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3D bioprinting of photocrosslinkable hydrogel constructs
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Recent Trends in Decellularized Extracellular Matrix Bioinks for 3D Printing: An Updated Review
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Self-citationBioprinted thrombosis-on-a-chip
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Self-citationXu, M., Girish, Y. R., Rakesh, K. P., Wu, P., Manukumar, H. M. G., Byrappa, S. M., Udayabhanu, & Byrappa, K. (2021) · Materials Today Communications · doi:10.1016/j.mtcomm.2021.102533 · Cited by 222 · see citing works
Cardiovascular disease models: A game changing paradigm in drug discovery and screening
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Natural Biomaterials and Their Use as Bioinks for Printing Tissues
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Current Strategies for the Manufacture of Small Size Tissue Engineering Vascular Grafts
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Extrusion and Microfluidic‐Based Bioprinting to Fabricate Biomimetic Tissues and Organs
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Self-citationTextile Technologies and Tissue Engineering: A Path Toward Organ Weaving
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Self-citationApplication of 3D Printing for Smart Objects with Embedded Electronic Sensors and Systems
Ota, H., Emaminejad, S., Gao, Y., Zhao, A., Wu, E. G., Challa, S., Chen, K., Fahad, H. M., Jha, A. K., Kiriya, D., et al. (2016) · Advanced Materials Technologies · doi:10.1002/admt.201600013 · Cited by 212 · see citing works
Three-dimensional bioprinting of gelatin methacryloyl (GelMA)
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AI-enabled organoids: Construction, analysis, and application
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The current state of scaffolds for musculoskeletal regenerative applications
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Advances in Carbon Nanotubes–Hydrogel Hybrids in Nanomedicine for Therapeutics
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Advancing the field of 3D biomaterial printing
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Evaluation of bioprinter technologies
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3D Bioprinting in Tissue Engineering for Medical Applications: The Classic and the Hybrid
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GelMA-collagen blends enable drop-on-demand 3D printablility and promote angiogenesis
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Materials and technical innovations in 3D printing in biomedical applications
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Ophthalmic gels: Past, present and future
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3D Bioprinting: A Novel Avenue for Manufacturing Tissues and Organs
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Directly coaxial 3D bioprinting of large-scale vascularized tissue constructs
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- Authors
- Bertassoni, L. E., Cecconi, M., Manoharan, V., Nikkhah, M., Hjortnaes, J., Cristino, A. L., Barabaschi, G., Demarchi, D., Dokmeci, M. R., Yang, Y., & Khademhosseini, A.
- Affiliations
- Brigham and Women's Hospital (US)
- Politecnico di Torino (IT)
- Stanford Medicine (US)
- Corresponding author
- Khademhosseini, Ali
- ORCID
- Venue
- Lab Chip
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2014
- Volume
- 14
- Issue
- 13
- Pages
- 2202-2211
- ISSN
- 1473-0189 (ISSN-L)
- 1473-0197
- PMC
- PMC4201051
- OpenAlex
- W2129322399
- Cited by
- 944
- References
- 50
- Citations by year
- 2026: 34 · 2025: 53 · 2024: 63 · 2023: 78 · 2022: 55 · 2021: 102 · 2020: 96 · 2019: 129 · 2018: 104 · 2017: 87 · 2016: 76 · 2015: 50 · 2014: 16
- FWCI
- 39.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Lab on a Chip (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- PORTO@Iris (submittedVersion)
- PORTO Publications Open Repository TOrino (Politecnico di Torino) (submittedVersion)
- Funders
- National Institutes of Health
- Defense Threat Reduction Agency
- Australian Research Council
- National Heart, Lung, and Blood Institute (HL-099073, R01HL099073)
- National Institute of General Medical Sciences (R01GM095906, GM095906)
- National Institute of Allergy and Infectious Diseases (R01AI081534, AI081534)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR057837, R01AR057837)
- National Institute of Biomedical Imaging and Bioengineering (EB02597)
- National Institute of Dental and Craniofacial Research (DE021468, R01DE021468)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- microchannel networks, vascularization, gelatin methacryloyl, poly(ethylene glycol) diacrylate, poly(ethylene glycol) dimethacrylate, endothelial monolayer, mass transfer, cell viability, cell differentiation, organ-on-a-chip
- MeSH terms
- Animals, Blood Vessel Prosthesis, Cell Line, Osteoblasts, Polyethylene Glycols, Sepharose, Hydrogels, Tissue Engineering, Mice
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