TY - JOUR
T1 - 3D bioprinting of mechanically tuned bioinks derived from cardiac decellularized extracellular matrix
AU - Shin, Yu Jung
AU - Shafranek, Ryan T.
AU - Tsui, Jonathan H.
AU - Walcott, Jelisha
AU - Nelson, Alshakim
AU - Kim, Deok Ho
N1 - Funding Information:
This work was supported by the National Institutes of Health grants R01HL146436 , R01HL94388 , R01NS094388 , UG3TR003271 , UH3TR003519 (to D.-H.K.) and the University of Washington Royalty Research Fund (to A.N.). This work was also supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute ( KHIDI ), funded by the Ministry of Health & Welfare, Republic of Korea ( HI19C0642 ).
Funding Information:
This work was supported by the National Institutes of Health grants R01HL146436, R01HL94388, R01NS094388, UG3TR003271, UH3TR003519 (to D.-H.K.) and the University of Washington Royalty Research Fund (to A.N.). This work was also supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI19C0642).
Publisher Copyright:
© 2020
PY - 2021/1/1
Y1 - 2021/1/1
N2 - 3D bioprinting is a powerful technique for engineering tissues used to study cell behavior and tissue properties in vitro. With the right formulation and printing parameters, bioinks can provide native biological and mechanical cues while allowing for versatile 3D structures that recapitulate tissue-level organization. Bio-based materials that support cellular adhesion, differentiation, and proliferation - including gelatin, collagen, hyaluronic acid, and alginate - have been successfully used as bioinks. In particular, decellularized extracellular matrix (dECM) has become a promising material with the unique ability to maintain both biochemical and topographical micro-environments of native tissues. However, dECM has shown technical limitations for 3D printing (3DP) applications posed by its intrinsically low mechanical stability. Herein, we report hydrogel bioinks composed of partially digested, porcine cardiac decellularized extracellular matrix (cdECM), Laponite-XLG nanoclay, and poly(ethylene glycol)-diacrylate (PEG-DA). The Laponite facilitated extrusion-based 3DP, while PEG-DA enabled photo-polymerization after printing. Improving upon previously reported bioinks derived from dECM, our bioinks combine extrudability, shape fidelity, rapid cross-linking, and cytocompatibility in a single formulation (> 97% viability of encapsulated human cardiac fibroblasts and > 94% viability of human induced pluripotent stem cell derived cardiomyocytes after 7 days). The compressive modulus of the cured hydrogel bioinks was tunable from 13.4-89 kPa by changing the concentration of PEG-DA in the bioink formulation. Importantly, this span of mechanical stiffness encompasses ranges of tissue stiffness from healthy (compressive modulus ~5-15 kPa) to fibrotic (compressive modulus ~30-100 kPa) cardiac tissue states. The printed constructs demonstrated shape fidelity, adaptability to different printing conditions, and high cell viability following extrusion and photo-polymerization, highlighting the potential for applications in modeling both healthy and fibrotic cardiac tissue.
AB - 3D bioprinting is a powerful technique for engineering tissues used to study cell behavior and tissue properties in vitro. With the right formulation and printing parameters, bioinks can provide native biological and mechanical cues while allowing for versatile 3D structures that recapitulate tissue-level organization. Bio-based materials that support cellular adhesion, differentiation, and proliferation - including gelatin, collagen, hyaluronic acid, and alginate - have been successfully used as bioinks. In particular, decellularized extracellular matrix (dECM) has become a promising material with the unique ability to maintain both biochemical and topographical micro-environments of native tissues. However, dECM has shown technical limitations for 3D printing (3DP) applications posed by its intrinsically low mechanical stability. Herein, we report hydrogel bioinks composed of partially digested, porcine cardiac decellularized extracellular matrix (cdECM), Laponite-XLG nanoclay, and poly(ethylene glycol)-diacrylate (PEG-DA). The Laponite facilitated extrusion-based 3DP, while PEG-DA enabled photo-polymerization after printing. Improving upon previously reported bioinks derived from dECM, our bioinks combine extrudability, shape fidelity, rapid cross-linking, and cytocompatibility in a single formulation (> 97% viability of encapsulated human cardiac fibroblasts and > 94% viability of human induced pluripotent stem cell derived cardiomyocytes after 7 days). The compressive modulus of the cured hydrogel bioinks was tunable from 13.4-89 kPa by changing the concentration of PEG-DA in the bioink formulation. Importantly, this span of mechanical stiffness encompasses ranges of tissue stiffness from healthy (compressive modulus ~5-15 kPa) to fibrotic (compressive modulus ~30-100 kPa) cardiac tissue states. The printed constructs demonstrated shape fidelity, adaptability to different printing conditions, and high cell viability following extrusion and photo-polymerization, highlighting the potential for applications in modeling both healthy and fibrotic cardiac tissue.
KW - 3D bioprinting
KW - Bioinks
KW - Cardiac tissue engineering
KW - Decellularized extracellular matrix
KW - Direct-ink writing
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U2 - 10.1016/j.actbio.2020.11.006
DO - 10.1016/j.actbio.2020.11.006
M3 - Article
C2 - 33166713
AN - SCOPUS:85096627435
VL - 119
SP - 75
EP - 88
JO - Acta Biomaterialia
JF - Acta Biomaterialia
SN - 1742-7061
ER -