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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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“Other microfabrication methods have been used in attempts to make complex, porous, tissue-engineered scaffolds, such as 3D projection stereolithography [42], and inkjet printing [43], to best replicate complex anatomic shaping and well-defined pore architecture [44]; however, an IVD construct with this level of micros…”
MethodCrosslinking strategies for biomimetic hydrogels in bone tissue engineering
Dibazar, Z. E., Zarei, M., Mohammadikhah, M., Oudah, S. K., Elyasi, M., Kokabi, H., Shahgolzari, M., Asl, L. D., & Azizy, M. (2023) · Biophysical Reviews · doi:10.1007/s12551-023-01141-x · Cited by 7
“3D printing and other methods have been developed to fabricate hydrogels with engineered morphology, porosity, and suitable mechanical strength for bone tissue engineering (Wang et al. 2021; Matai et al. 2020; Gauvin et al. 2012).”
Harnessing Next‐Generation 3D Cancer Models to Elucidate Tumor‐Microbiome Crosstalk
Buzhor, M. G., Longobardi, G., Kandli, O., Krinsky, A., Avramoff, O., Katyal, A., Salomon, K., Miari, A., Venkert, D., Barnatan, T. T., et al. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202503198 · Cited by 7
Brown, N. E., Ellerbe, L. R., Hollister, S. J., & Temenoff, J. S. (2024) · Annals of Biomedical Engineering · doi:10.1007/s10439-024-03530-z · Cited by 7
“In addition, using standard bulk fabrication methods, it is difficult to fabricate hydrogels in complex anatomic geometries with precise cell and extracellular matrix (ECM) organization [26, 46].”
Półtorak, M., Banatkiewicz, P., Półtorak, Ł., Sobolewski, P., Zimoń, D., Szwast, M., & Walecka, I. (2024) · Journal of Contemporary Brachytherapy · doi:10.5114/jcb.2024.141420 · Cited by 7
Ozbolat, I. T. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803010-3.00003-2 · Cited by 7
Cui, C., Yin, J., & Han, L. (2020) · Advanced Functional Materials · doi:10.1002/adfm.202003959 · Cited by 7
Hydrogels for Stem Cell Fate Control and Delivery in Regenerative Medicine
Toh, W. S., Toh, Y., & Loh, X. J. (2014) · Series in bioengineering · doi:10.1007/978-981-287-152-7_8 · Cited by 7
Design of multi-scaffold fabrication system for various 3D scaffolds
Sa, M., & Kim, J. Y. (2013) · Journal of Mechanical Science and Technology · doi:10.1007/s12206-013-0810-7 · Cited by 7
Three-dimensional printing of biocompatible scaffolds for tissue engineered constructs
Jiang, D. C. P., Jeng, Y.-C., Коновалов, А. Н., Mironov, A. V., Popov, V. K., Chen, Y. Y., Cheng, Y., & Shafikova, R. (2016) · Bulletin of the Russian Academy of Sciences Physics · doi:10.3103/s1062873816040092 · Cited by 7
Self-citation3D Printing and Nanomanufacturing
Zhu, W. Z., Ock, J., Ma, X., Li, W., & Chen, S. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-800547-7.00002-3 · Cited by 7
Self-citationNanomaterials in 3D bioprinting
Manavitehrani, I., Nasiri, N., & Parviz, M. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813892-2.00006-9 · Cited by 7
Coping with Integrating Low-Cost 3D Printing and Surface Models: A Case Study on Prusa i3
Brus, J., & Barvíř, R. (2015) · Lecture notes in geoinformation and cartography · doi:10.1007/978-3-319-18407-4_5 · Cited by 7
Retracted: Endothelial/Mesenchymal Stem Cell Crosstalk Within Bioprinted Cocultures
Santoro, M., Awosika, T. O., Snodderly, K. L., Hurley-Novatny, A. C., Lerman, M. J., & Fisher, J. P. (2019) · Tissue Engineering Part A · doi:10.1089/ten.tea.2019.0175 · Cited by 7
“Both cells were loaded in GelMA, a hydrogel system successfully used in different TE strategies 8,12,13 and, subsequently, processed through extrusion-based bioprinting.”
RetractedBahraminasab, M., Arabhalvaei, M., & Ghanbari, M. A. (2025) · BioMedical Engineering OnLine · doi:10.1186/s12938-025-01475-5 · Cited by 6
Bhardwaj, N., Dey, S., Bhar, B., & Mandal, B. B. (2023) · Progress in Biomedical Engineering · doi:10.1088/2516-1091/ad10b4 · Cited by 9
“%) and resolution (as low as 100 µ m) within 30 min using STL [70].”
MethodBiofabrication of brain-like living tissue: structure to intelligence
Wang, L., Wang, S., Liu, Y., Zhang, B., Pan, Z., Bai, L., Yao, S., Zhang, C., Xie, H., He, J., et al. (2025) · International Journal of Extreme Manufacturing · doi:10.1088/2631-7990/ada7a8 · Cited by 7
“This platform allows for layer-by-layer engineering design of scaffolds smaller than 200 µ m, and good cell adhesion, growth, and uniform distribution have been achieved during cultivation [155].”
3D functional scaffolds for cartilage tissue engineering
Lee, K.-X. A., Ng, H. Y., Wei, L.-J., & Shen, Y. (2017) · Elsevier eBooks · doi:10.1016/b978-0-08-100979-6.00016-1 · Cited by 8
Collagen scaffold impregnated with borosilicate bioactive glass for endometrial healing
Rezaeipour, Y., Alizadeh, P., & Keshavarz, M. (2023) · Applied Materials Today · doi:10.1016/j.apmt.2022.101727 · Cited by 6
Spatial and Electrical Factors Regulating Cardiac Regeneration and Assembly
Pahnke, A., Montgomery, M., & Radisic, M. (2014) · Springer eBooks · doi:10.1007/978-3-319-10972-5_3 · Cited by 6
Limongi, T. (2015) · Journal of Tissue Science & Engineering · doi:10.4172/2157-7552.1000145 · Cited by 6
“The latest improvements in biomaterials design and characterization, along with the impressive progress achieved in nanotechnologies and microfabrication techniques, have led to the production of highly performant micro- and nano-structured materials and devices designed for a variety of biomedical tissue engineering…”
BackgroundEvdokimov, P. V., Tikhonova, S. A., Киселева, А. К., Filippov, Y. Y., Novoseletskaya, E. S., Efimenko, A. Y., & Putlayev, V. I. (2021) · Russian Journal of Inorganic Chemistry · doi:10.1134/s0036023621110061 · Cited by 6
Pountos, I., Tellisi, N., Darabi, M., Erdem, A., Mohamed, T., Guvendiren, M., & Ashammakhi, N. (2020) · Digital Surgery · doi:10.1007/978-3-030-49100-0_16 · Cited by 1
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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