Biofabrication strategies for 3D in vitro models and regenerative medicine
Open accessAbstract
Organs are complex systems composed of different cells, proteins and signalling molecules that are arranged in a highly ordered structure to orchestrate a myriad of functions in our body. Biofabrication strategies can be applied to engineer 3D tissue models in vitro by mimicking the structure and function of native tissue through the precise deposition and assembly of materials and cells. This approach allows the spatiotemporal control over cell–cell and cell–extracellular matrix communication and thus the recreation of tissue-like structures. In this Review, we examine biofabrication strategies for the construction of functional tissue replacements and organ models, focusing on the development of biomaterials, such as supramolecular and photosensitive materials, that can be processed using biofabrication techniques. We highlight bioprinted and bioassembled tissue models and survey biofabrication techniques for their potential to recreate complex tissue properties, such as shape, vasculature and specific functionalities. Finally, we discuss challenges, such as scalability and the foreign body response, and opportunities in the field and provide an outlook to the future of biofabrication in regenerative medicine. Biofabrication can be applied to replicate tissues and organs for regenerative medicine and for the creation of 3D in vitro tissue models. In this Review, the recent advances in biomaterials and biofabrication technologies are discussed, and challenges and opportunities are highlighted.
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Commonly chosen materials include Matrigel, other natural biomaterials (gelatin, fibrin, collagen, alginate, chitosan, hyaluronic acid), and synthetic polymers (PEG, PCL).
“Commonly chosen materials include Matrigel, other natural biomaterials (e.g., gelatin, fi brin, collagen, alginate, chitosan, hyaluronic acid), and synthetic polymers (e.g., PEG, PCL) [40,87].”
From 3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions (2021) · cites this paper as [40]
The Natural biomaterials section (page unavailable) lists collagen, gelatin, alginate and hyaluronic acid as bioink materials, while other sections describe Matrigel, PEG and PCL in biofabrication applications. Our copy does not substantiate fibrin as a commonly chosen material, and chitosan appears only in a reference title rather than in the review’s discussion of material choices. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCommon limitations of 3D bioprinting include slow printing speeds, development of nontoxic and printable bioinks, and insufficient reproducibility to create standard models.
“Common limitations, however, include slow printing speeds, development of nontoxic and printable bioinks, and insuf fi cient reproducibility to create standard models [38,40].”
From 3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions (2021) · cites this paper as [40]
The ‘Scalability and manufacturing time’ section identifies long manufacturing times as a limitation, while ‘Cells in bioinks’ and ‘High-viscosity and low-viscosity materials’ discuss cell toxicity and printability challenges. The paper does not identify insufficient reproducibility as a barrier to standard models; its ‘Cancer models’ section instead describes bioprinting as a way to create reproducible tumour models. Our copy provides section labels but no page numbers for these passages. (LLM, conf=0.86)
Experimental — accuracy not yet measuredOver past decades, multiple 3D bioprinting methods have been improved to allow design of complex cell-laden 3D constructs.
“Over the past decades, multiple 3D bioprinting methods have been improved to allow the design of complex cell-laden 3D constructs.”
From 3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions (2021) · cites this paper as [40]
Each 3D bioprinting technology is application-specific and choice depends on type of bioink used.
“Each of these technologies is application-speci fi c and the choice depends on the type of bioink used [40,87].”
From 3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions (2021) · cites this paper as [40]
Laser-assisted bioprinting uses high-intensity laser to deposit less-viscous bioinks for cell patterning, preserving high cell viability.
“In laser-assisted bioprinting, a high-intensity laser is used to deposit less-viscous bioinks for cell patterning, thereby preserving high cell viability.”
From 3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions (2021) · cites this paper as [40]
The Photodegradable materials section describes using a pulsed laser to pattern channels in existing hydrogels, not to deposit bioinks. The High-viscosity and low-viscosity materials and Cells in bioinks sections discuss printing low-viscosity materials and maintaining cell viability, but do not connect either to laser-assisted deposition. Searches for laser-assisted bioprinting and laser printing found no passage establishing the claimed method or viability outcome; page numbers were unavailable in our copy. (LLM, conf=0.72)
Experimental — accuracy not yet measured
Laser-assisted bioprinting is the most complex and expensive method of printing.
“Despite its cell-compatibility, this is the most complex and expensive method of printing [40,90].”
From 3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions (2021) · cites this paper as [40]
The section on Photodegradable materials describes laser-based patterning as high-resolution, but does not compare its complexity or cost with other printing methods. Searches for laser-assisted bioprinting, expense, and comparative complexity found no passage in our copy supporting the claim that it is the most complex and expensive method. (LLM, conf=0.72)
Experimental — accuracy not yet measuredBiofabrication technologies such as bioprinting enable programmed assembly of cells into complex 3D geometries.
“Biofabrication technologies, such as bioprinting, enable programmed assembly of cells into complex 3D geometries24,25.”
From 3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels (2021) · cites this paper as [25]
Various biofunctional materials and cell types can be printed simultaneously onto a substrate of cell-compatible biomaterials to build 3D complex constructs with good spatial resolution and reproducibility.
“Various biofunctional materials and cell types can thus be printed simultaneously onto a substrate of cell-compatible biomaterials to build 3D complex constructs with good spatial resolution and reproducibility (Fig. 3a)130,148–151.”
From Tumor-on-a-chip: from bioinspired design to biomedical application (2021) · cites this paper as [148]
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Self-citationEngineered materials for organoid systems
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3D In Vitro Model (R)evolution: Unveiling Tumor–Stroma Interactions
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“this is the most complex and expensive method of printing [40,90].”
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Dynamic and reconfigurable materials from reversible network interactions
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Noninvasive in vivo 3D bioprinting
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3D bioprinting for reconstituting the cancer microenvironment
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Tailoring Gelation Mechanisms for Advanced Hydrogel Applications
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3D Bioprinted Human Skeletal Muscle Constructs for Muscle Function Restoration
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Self-citationExpanding and optimizing 3D bioprinting capabilities using complementary network bioinks
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Self-citationA Photo‐Crosslinkable Kidney ECM‐Derived Bioink Accelerates Renal Tissue Formation
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Self-citation3D Bioprinted in vitro metastatic models via reconstruction of tumor microenvironments
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Self-citation3D printing for preoperative planning and surgical training: a review
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Advances in 3D bioprinting of tissues/organs for regenerative medicine and in-vitro models.
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Additive Manufacturing of Precision Biomaterials
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Self-citationComplexation-induced resolution enhancement of 3D-printed hydrogel constructs
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Progress and prospects for accelerating materials science with automated and autonomous workflows
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Dynamic Bioinks to Advance Bioprinting
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Self-citationOrgan-on-a-Chip for Cancer and Immune Organs Modeling
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Intravital three-dimensional bioprinting
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Strategies to use fibrinogen as bioink for 3D bioprinting fibrin-based soft and hard tissues
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Optical Forces: From Fundamental to Biological Applications
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Self-citationHyaluronic acid as a bioink for extrusion-based 3D printing
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Advances in the Fabrication of Biomaterials for Gradient Tissue Engineering
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Electrical stimulation system based on electroactive biomaterials for bone tissue engineering
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3D bioprinting in cardiac tissue engineering
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Light-based vat-polymerization bioprinting
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Direct 3D Printed Biomimetic Scaffolds Based on Hydrogel Microparticles for Cell Spheroid Growth
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Self-enhancing sono-inks enable deep-penetration acoustic volumetric printing
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3D bioprinting: current status and trends—a guide to the literature and industrial practice
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Nanoengineered Osteoinductive Bioink for 3D Bioprinting Bone Tissue
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Biofabrication of natural hydrogels for cardiac, neural, and bone Tissue engineering Applications
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Current standards and ethical landscape of engineered tissues—3D bioprinting perspective
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3D printing biomimetic materials and structures for biomedical applications
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3D bioprinting via an in situ crosslinking technique towards engineering cartilage tissue
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Volumetric additive manufacturing of pristine silk-based (bio)inks
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Self-citation
- Authors
- Moroni, L., Burdick, J. A., Highley, C., Lee, S. J., Morimoto, Y., Takeuchi, S., & Yoo, J. J.
- Affiliations
- Maastricht University (NL)
- University of Pennsylvania (US)
- Wake Forest University Health Sciences (US)
- Institute of Industrial Science, The University of Tokyo (JP)
- Corresponding author
- Moroni, Lorenzo
- ORCID
- Venue
- Nature Reviews Materials
- Published
- 2018-04-26
- Volume
- 3
- Issue
- 5
- Pages
- 21-37
- ISSN
- 2058-8437 (ISSN-L)
- PMC
- PMC6586020
- OpenAlex
- W2799893835
- Cited by
- 753
- References
- 243
- Citations by year
- 2026: 57 · 2025: 103 · 2024: 89 · 2023: 104 · 2022: 104 · 2021: 129 · 2020: 97 · 2019: 54 · 2018: 13 · 2017: 1 · 2012: 1
- FWCI
- 5.97
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-05-03)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature Reviews Materials (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Publications (Maastricht University) (submittedVersion, cc-by)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- AO Foundation
- National Institutes of Health
- Japan Society for the Promotion of Science (16H06329)
- National Institute of Biomedical Imaging and Bioengineering (P41EB023833)
- H2020 European Research Council (637308)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- biofabrication, regenerative medicine, bioprinting, biomaterials, supramolecular materials, photoresponsive materials, tissue engineering, vascular system, foreign body reaction, scalability, organ models
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