A hydrogel bioink toolkit for mimicking native tissue biochemical and mechanical properties in bioprinted tissue constructs
Open accessAbstract
Advancement of bioprinting technology is limited by the availability of materials that both facilitate bioprinting logistics as well as support cell viability and function by providing tissue-specific cues. Herein we describe a modular hyaluronic acid (HA) and gelatin-based hydrogel toolbox comprised of a 2-crosslinker, 2-stage polymerization technique, and the capability to provide tissue specific biochemically and mechanically accurate signals to cells within biofabricated tissue constructs. First, we prepared and characterized several tissue-derived decellularized extracellular matrix-based solutions, which contain complex combinations of growth factors, collagens, glycosaminoglycans, and elastin. These solutions can be incorporated into bioinks to provide the important biochemical cues of different tissue types. Second, we employed combinations of PEG-based crosslinkers with varying molecular weights, geometries (linear, 4-arm, and 8-arm), and functional groups to yield hydrogel bioinks that supported extrusion bioprinting and the capability to achieve final construct shear stiffness values ranging from approximately 100 Pa to 20 kPa. Lastly, we integrated these hydrogel bioinks with a 3-D bioprinting platform, and validated their use by bioprinting primary liver spheroids in a liver-specific bioink to create in vitro liver constructs with high cell viability and measurable functional albumin and urea output. This hydrogel bioink system has the potential to be a versatile tool for biofabrication of a wide range of tissue construct types. Statement of significance Biochemical and mechanical factors both have important implications in guiding the behavior of cells in vivo, yet both realms are rarely considered together in the context of biofabrication in vitro tissue construct models. We describe a modular hydrogel system that (1) facilitates extrusion bioprinting of cell-laden hydrogels, (2) incorporates tissue-specific factors derived from decellularized tissue extracellular matrix, thus mimicking biochemical tissue profile, and (3) allows control over mechanical properties to mimic the tissue stiffness. We believe that employing this technology to attend to both the biochemical and mechanical profiles of tissues, will allow us to more accurately recapitulate the in vivo environment of tissues while creating functional 3-D in vitro tissue constructs that can be used as disease models, personalized medicine, and in vitro drug and toxicology screening systems.
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This heterogeneity is likely the reason why there have been conflicting accounts regarding growth factor preservation, such as HGF and FGF.
“This heterogeneity is likely the reason why there have been conflicting accounts regarding growth factor preservation, such as that of hepatocyte growth factor (HGF) and fibroblast growth factor (FGF), both critical in the function and regeneration of hepatocytes [82].”
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- Authors
- Skardal, A., Devarasetty, M., Kang, H.-W., Mead, I., Bishop, C., Shupe, T., Lee, S. J., Jackson, J., Yoo, J., Soker, S., & Atala, A.
- Affiliations
- Wake Forest University Health Sciences (US)
- Corresponding author
- Skardal, Aleksander
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 25
- Pages
- 24-34
- ISSN
- 1742-7061 (ISSN-L)
- OpenAlex
- W1004941119
- Cited by
- 428
- References
- 2
- Citations by year
- 2026: 19 · 2025: 22 · 2024: 21 · 2023: 42 · 2022: 37 · 2021: 62 · 2020: 71 · 2019: 60 · 2018: 47 · 2017: 28 · 2016: 15 · 2015: 2
- FWCI
- 15.26
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Acta Biomaterialia (publishedVersion)
- PubMed (publishedVersion)
- Scholarworks@UNIST (Ulsan National Institute of Science and Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- Defense Threat Reduction Agency
- National Institute of Biomedical Imaging and Bioengineering (T32EB014836)
- 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
- hydrogel bioinks, hyaluronic acid, gelatin, decellularized extracellular matrix, extrusion-based bioprinting, tissue stiffness, liver spheroids, cell viability
- MeSH terms
- Albumins, Animals, Biomechanical Phenomena, Extracellular Matrix, Humans, Polyethylene Glycols, Rheology, Solutions, Tissue Survival, Urea, Spheroids, Cellular, Hydrogel, Polyethylene Glycol Dimethacrylate, Tissue Engineering, Sus scrofa, Tissue Scaffolds, Bioprinting
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