A hydrogel bioink toolkit for mimicking native tissue biochemical and mechanical properties in bioprinted tissue constructs

Aleksander Skardal, Mahesh Devarasetty, Hyun Wook Kang, Ivy Mead, Colin Bishop, Thomas Shupe, Sang Jin Lee, John Jackson, James Yoo, Shay Soker, Anthony Atala

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)24-34
Number of pages11
JournalActa Biomaterialia
Volume25
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Fingerprint

Hydrogel
Hydrogels
Bioprinting
Tissue
Mechanical properties
Liver
Cells
Cues
Extracellular Matrix
Cell Survival
Extrusion
Stiffness
Technology
Elastin
Precision Medicine
Preclinical Drug Evaluations
Hyaluronic acid
Thromboplastin
Hyaluronic Acid
Gelatin

Keywords

  • Bioink
  • Bioprinting
  • Elastic modulus
  • Extracellular matrix
  • Hydrogel

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Biotechnology
  • Biochemistry
  • Molecular Biology

Cite this

A hydrogel bioink toolkit for mimicking native tissue biochemical and mechanical properties in bioprinted tissue constructs. / Skardal, Aleksander; Devarasetty, Mahesh; Kang, Hyun Wook; Mead, Ivy; Bishop, Colin; Shupe, Thomas; Lee, Sang Jin; Jackson, John; Yoo, James; Soker, Shay; Atala, Anthony.

In: Acta Biomaterialia, Vol. 25, 01.10.2015, p. 24-34.

Research output: Contribution to journalArticle

Skardal, A, Devarasetty, M, Kang, HW, Mead, I, Bishop, C, Shupe, T, Lee, SJ, Jackson, J, Yoo, J, Soker, S & Atala, A 2015, 'A hydrogel bioink toolkit for mimicking native tissue biochemical and mechanical properties in bioprinted tissue constructs', Acta Biomaterialia, vol. 25, pp. 24-34. https://doi.org/10.1016/j.actbio.2015.07.030
Skardal, Aleksander ; Devarasetty, Mahesh ; Kang, Hyun Wook ; Mead, Ivy ; Bishop, Colin ; Shupe, Thomas ; Lee, Sang Jin ; Jackson, John ; Yoo, James ; Soker, Shay ; Atala, Anthony. / A hydrogel bioink toolkit for mimicking native tissue biochemical and mechanical properties in bioprinted tissue constructs. In: Acta Biomaterialia. 2015 ; Vol. 25. pp. 24-34.
@article{c64dc499b9884f7ea66ed6ed932ce7a8,
title = "A hydrogel bioink toolkit for mimicking native tissue biochemical and mechanical properties in bioprinted tissue constructs",
abstract = "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.",
keywords = "Bioink, Bioprinting, Elastic modulus, Extracellular matrix, Hydrogel",
author = "Aleksander Skardal and Mahesh Devarasetty and Kang, {Hyun Wook} and Ivy Mead and Colin Bishop and Thomas Shupe and Lee, {Sang Jin} and John Jackson and James Yoo and Shay Soker and Anthony Atala",
year = "2015",
month = "10",
day = "1",
doi = "10.1016/j.actbio.2015.07.030",
language = "English (US)",
volume = "25",
pages = "24--34",
journal = "Acta Biomaterialia",
issn = "1742-7061",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - A hydrogel bioink toolkit for mimicking native tissue biochemical and mechanical properties in bioprinted tissue constructs

AU - Skardal, Aleksander

AU - Devarasetty, Mahesh

AU - Kang, Hyun Wook

AU - Mead, Ivy

AU - Bishop, Colin

AU - Shupe, Thomas

AU - Lee, Sang Jin

AU - Jackson, John

AU - Yoo, James

AU - Soker, Shay

AU - Atala, Anthony

PY - 2015/10/1

Y1 - 2015/10/1

N2 - 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.

AB - 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.

KW - Bioink

KW - Bioprinting

KW - Elastic modulus

KW - Extracellular matrix

KW - Hydrogel

UR - http://www.scopus.com/inward/record.url?scp=84940901044&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940901044&partnerID=8YFLogxK

U2 - 10.1016/j.actbio.2015.07.030

DO - 10.1016/j.actbio.2015.07.030

M3 - Article

AN - SCOPUS:84940901044

VL - 25

SP - 24

EP - 34

JO - Acta Biomaterialia

JF - Acta Biomaterialia

SN - 1742-7061

ER -