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Microfabrication of complex porous tissue engineering scaffolds using 3D projection stereolithography
Open accessAbstract
The success of tissue engineering will rely on the ability to generate complex, cell seeded three-dimensional (3D) structures. Therefore, methods that can be used to precisely engineer the architecture and topography of scaffolding materials will represent a critical aspect of functional tissue engineering. Previous approaches for 3D scaffold fabrication based on top-down and process driven methods are often not adequate to produce complex structures due to the lack of control on scaffold architecture, porosity, and cellular interactions. The proposed projection stereolithography (PSL) platform can be used to design intricate 3D tissue scaffolds that can be engineered to mimic the microarchitecture of tissues, based on computer aided design (CAD). The PSL system was developed, programmed and optimized to fabricate 3D scaffolds using gelatin methacrylate (GelMA). Variation of the structure and prepolymer concentration enabled tailoring the mechanical properties of the scaffolds. A dynamic cell seeding method was utilized to improve the coverage of the scaffold throughout its thickness. The results demonstrated that the interconnectivity of pores allowed for uniform human umbilical vein endothelial cells (HUVECs) distribution and proliferation in the scaffolds, leading to high cell density and confluency at the end of the culture period. Moreover, immunohistochemistry results showed that cells seeded on the scaffold maintained their endothelial phenotype, demonstrating the biological functionality of the microfabricated GelMA scaffolds.
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“Results from 3D studies demonstrate that increasing the dimensionality of extracellular matrix (ECM) around cells from 2D to 3D can significantly impact cell proliferation, differentiation, mechano-responses, and cell survival (2,10,41).”
From Modeling physiological events in 2D vs. 3D cell culture (2017) · cites this paper as [41]
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Jian, H., Wang, M., Wang, S., Wang, A., & Bai, S. (2018) · Bio-Design and Manufacturing · doi:10.1007/s42242-018-0006-1 · Cited by 82
3D bioprinting for modelling vasculature
Sasmal, P. K., Datta, P., Wu, Y. B., & Ozbolat, I. T. (2018) · Microphysiological Systems · doi:10.21037/mps.2018.10.02 · Cited by 85
“In other attempts, Human Umbilical Vein Endothelial Cells (HUVECs) were seeded on patterns created by photolithography (13).”
BackgroundFang, Y., Guo, Y., Liu, T., Xu, R., Mao, S., Mo, X., Zhang, T., Ouyang, L., Xiong, Z., & Sun, W. (2022) · Chinese Journal of Mechanical Engineering Additive Manufacturing Frontiers · doi:10.1016/j.cjmeam.2022.100011 · Cited by 86
Numerical and experimental evaluation of TPMS Gyroid scaffolds for bone tissue engineering
Castro, A. P. G., Ruben, R. B., Gonçalves, S., Pinheiro, J., Guedes, J. M., & Fernandes, P. R. (2019) · Computer Methods in Biomechanics & Biomedical Engineering · doi:10.1080/10255842.2019.1569638 · Cited by 79
“Some of the existent TPMS scaffolds types are Schwartz D, Schwartz P or Gyroid (Rajagopalan & Robb 2006; Gauvin et al. 2012; Giannitelli et al. 2014; Blanquer et al. 2017).”
BackgroundLight-based 3D printing of hydrogels with high-resolution channels
Benjamin, A. D., Abbasi, R., Owens, M., Olsen, R. J., Walsh, D. J., LeFevre, T. B., & Wilking, J. N. (2018) · Biomedical Physics & Engineering Express · doi:10.1088/2057-1976/aad667 · Cited by 78
Yi, S., Liu, Q., Luo, Z., He, J. J., Ma, H., Li, W., Wang, D., Zhou, C., Garciamendez‐Mijares, C. E., Hou, L., et al. (2022) · Small · doi:10.1002/smll.202106357 · Cited by 79
In Situ Organ-Specific Vascularization in Tissue Engineering
Fu, J., & Wang, D. (2018) · Trends in biotechnology · doi:10.1016/j.tibtech.2018.02.012 · Cited by 80
“More recently, with the applications of digital-mirror devices and projection optics in photolithography, light patterns can be even directly projected onto photocrosslinkable biomaterials without a mask, which enables 3D layer-by-layer continuous photolithography to be feasible [18,19].”
BackgroundJin, Y. Q., Kong, H., Zhou, X., Li, G., & Du, J. (2020) · Materials · doi:10.3390/ma13173844 · Cited by 76
“Furthermore, the proposed structures can be easily extended to other AM techniques with other biomaterials, such as extrusion-based technique [46] and projection stereolithography [47] for more advanced TE applications.”
MethodTavafoghi, M., Darabi, M. A., Mahmoodi, M., Tutar, R., Xu, C., Mirjafari, A., Billi, F., Święszkowski, W., Nasrollahi, F., Ahadian, S., et al. (2021) · Biofabrication · doi:10.1088/1758-5090/ac0b9a · Cited by 79
Self-citationAdvancing Tissue Engineering: A Tale of Nano‐, Micro‐, and Macroscale Integration
Leijten, J., Rouwkema, J., Zhang, Y. S., Nasajpour, A., Dokmeci, M. R., & Khademhosseini, A. (2015) · Small · doi:10.1002/smll.201501798 · Cited by 76
Self-citationKang, W., Bi, B., Zhuo, R., & Jiang, X. (2016) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2016.12.032 · Cited by 76
3D Printing/Bioprinting Based Tailoring of in Vitro Tissue Models: Recent Advances and Challenges
Mehrotra, S., Moses, J. C., Bandyopadhyay, A., & Mandal, B. B. (2019) · ACS Applied Bio Materials · doi:10.1021/acsabm.9b00073 · Cited by 75
3D printing of PLGA scaffolds for tissue engineering
Mironov, A. V., Grigoryev, A. M., Кротова, Л. И., Skaletsky, N. N., Popov, V. K., & Sevastianov, V. I. (2016) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.35871 · Cited by 75
Advanced Polymers for Three-Dimensional (3D) Organ Bioprinting
Wang, X. (2019) · Micromachines · doi:10.3390/mi10120814 · Cited by 76
“, gelatin methacrylamide or gelatin methacryloyl, GelMA) using irreversible ultraviolet (UV) photopolymerization techniques [99].”
MethodFabricating Lattice Structures via 3D Printing: The Case of Porous Bio-Engineered Scaffolds
Kantaros, A., & Piromalis, D. D. (2021) · Applied Mechanics · doi:10.3390/applmech2020018 · Cited by 74
Fabrication of circular microfluidic network in enzymatically-crosslinked gelatin hydrogel
He, J., Chen, R., Lu, Y., Li, Z., Liu, Y., Li, D., & Jin, Z. (2015) · Materials Science and Engineering C · doi:10.1016/j.msec.2015.09.104 · Cited by 76
Charbonnier, B., Manassero, M., Bourguignon, M., Decambron, A., El‐Hafci, H., Morin, C., Leon, D., Bensidoum, M., Corsia, S., Petite, H., et al. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.03.016 · Cited by 73
“Easily 3D-printed with either polymeric [7,8,16], metallic [17], [18], [19], [20], or composite [21], [22], [23] materials, TPMS structures are difficult to produce with CaP [24,25], due to the inability of most present-day AM to process bioceramics.”
BackgroundGhorbanian, S., Qasaimeh, M. A., Akbari, M., Tamayol, A., & Juncker, D. (2014) · Biomedical Microdevices · doi:10.1007/s10544-014-9842-8 · Cited by 73
Engineering Photocrosslinkable Bicomponent Hydrogel Constructs for Creating 3D Vascularized Bone
Kazemzadeh‐Narbat, M., Rouwkema, J., Annabi, N., Cheng, H., Ghaderi, M., Cha, B., Aparnathi, M. K., Khalilpour, A., Byambaa, B., Jabbari, E., et al. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201601122 · Cited by 73
Self-citationBiomimicry, Biofabrication, and Biohybrid Systems: The Emergence and Evolution of Biological Design
Raman, R., & Bashir, R. (2017) · Advanced Healthcare Materials · doi:10.1002/adhm.201700496 · Cited by 76
Recent advances in ink-based additive manufacturing for porous structures
Guo, Z., & Zhou, C. (2021) · Additive manufacturing · doi:10.1016/j.addma.2021.102405 · Cited by 75
A ‘print–pause–print’ protocol for 3D printing microfluidics using multimaterial stereolithography
Kim, Y. T., Ahmadianyazdi, A., & Folch, A. (2023) · Nature Protocols · doi:10.1038/s41596-022-00792-6 · Cited by 75
Metadata
- Authors
- Gauvin, R., Chen, Y.-C., Lee, J. W., Soman, P., Zorlutuna, P., Nichol, J. W., Bae, H., Chen, S., & Khademhosseini, A.
- Affiliations
- Brigham and Women's Hospital (US)
- University of California San Diego (US)
- Corresponding author
- Chen, Ying-Chieh
- Chen, Shaochen
- Khademhosseini, Ali
- ORCID
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 33
- Issue
- 15
- Pages
- 3824-3834
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC3766354
- OpenAlex
- W2164279637
- Cited by
- 641
- References
- 68
- Citations by year
- 2026: 13 · 2025: 30 · 2024: 28 · 2023: 42 · 2022: 57 · 2021: 58 · 2020: 66 · 2019: 69 · 2018: 59 · 2017: 53 · 2016: 43 · 2015: 43 · 2014: 41 · 2013: 28 · 2012: 10
- FWCI
- 22.25
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (HL099073, EB012597, HL092836)
- Fonds Québécois de la Recherche sur la Nature et les Technologies
- National Science Foundation (DMR0847287)
- Office of Naval Research
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
- Keywords
- projection stereolithography, tissue engineering scaffolds, gelatin methacryloyl, 3D microfabrication, porous scaffolds, scaffold porosity, human umbilical vein endothelial cells, endothelial phenotype, scaffold mechanical properties, scaffold architecture
- MeSH terms
- Fluorescent Antibody Technique, Humans, Porosity, Microscopy, Confocal, Tissue Engineering, Green Fluorescent Proteins, Tissue Scaffolds, Microtechnology, Human Umbilical Vein Endothelial Cells
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