TY - JOUR
T1 - Convergence of melt electrowriting and extrusion-based bioprinting for vascular patterning of a myocardial construct
AU - Ainsworth, Madison Jade
AU - Chirico, Nino
AU - de Ruijter, Mylène
AU - Hrynevich, Andrei
AU - Dokter, Inge
AU - Sluijter, Joost P.G.
AU - Malda, Jos
AU - van Mil, Alain
AU - Castilho, Miguel
N1 - Funding Information:
MJA and NC are shared first authors. AvM and MC are shared senior authors. The authors would like to gratefully acknowledge the financial support from the EU’s H2020 program under Grant Agreement #801540 (Marie Skłodowska-Curie RESCUE co-fund grant), and #874827 (BRAV∃), as well as the Gravitation Program ‘Materials Driven Regeneration’, funded by the Netherlands Organization for Scientific Research (024.003.013). MC acknowledges the financial support from the Reprint project (OCENW.XS5.161) by the Netherlands Organization for Scientific Research.
Publisher Copyright:
© 2023 The Author(s). Published by IOP Publishing Ltd.
PY - 2023/7/1
Y1 - 2023/7/1
N2 - To progress cardiac tissue engineering strategies closer to the clinic, thicker constructs are required to meet the functional need following a cardiac event. Consequently, pre-vascularization of these constructs needs to be investigated to ensure survival and optimal performance of implantable engineered heart tissue. The aim of this research is to investigate the potential of combining extrusion-based bioprinting (EBB) and melt electrowriting for the fabrication of a myocardial construct with a precisely patterned pre-vascular pathway. Gelatin methacryloyl (GelMA) was investigated as a base hydrogel for the respective myocardial and vascular bioinks with collagen, Matrigel and fibrinogen as interpenetrating polymers to support myocardial functionality. Subsequently, extrusion-based printability and viability were investigated to determine the optimal processing parameters for printing into melt electrowritten meshes. Finally, an anatomically inspired vascular pathway was implemented in a dual EBB set-up into melt electrowritten meshes, creating a patterned pre-vascularized myocardial construct. It was determined that a blend of 5% GelMA and 0.8 mg·ml−1 collagen with a low crosslinked density was optimal for myocardial cellular arrangement and alignment within the constructs. For the vascular fraction, the optimized formulation consisted of 5% GelMA, 0.8 mg·ml−1 collagen and 1 mg·ml−1 fibrinogen with a higher crosslinked density, which led to enhanced vascular cell connectivity. Printability assessment confirmed that the optimized bioinks could effectively fill the microfiber mesh while supporting cell viability (∼70%). Finally, the two bioinks were applied using a dual EBB system for the fabrication of a pre-vascular pathway with the shape of a left anterior descending artery within a myocardial construct, whereby the distinct cell populations could be visualized in their respective patterns up to D14. This research investigated the first step towards developing a thick engineered cardiac tissue construct in which a pre-vascularization pathway is fabricated within a myocardial construct.
AB - To progress cardiac tissue engineering strategies closer to the clinic, thicker constructs are required to meet the functional need following a cardiac event. Consequently, pre-vascularization of these constructs needs to be investigated to ensure survival and optimal performance of implantable engineered heart tissue. The aim of this research is to investigate the potential of combining extrusion-based bioprinting (EBB) and melt electrowriting for the fabrication of a myocardial construct with a precisely patterned pre-vascular pathway. Gelatin methacryloyl (GelMA) was investigated as a base hydrogel for the respective myocardial and vascular bioinks with collagen, Matrigel and fibrinogen as interpenetrating polymers to support myocardial functionality. Subsequently, extrusion-based printability and viability were investigated to determine the optimal processing parameters for printing into melt electrowritten meshes. Finally, an anatomically inspired vascular pathway was implemented in a dual EBB set-up into melt electrowritten meshes, creating a patterned pre-vascularized myocardial construct. It was determined that a blend of 5% GelMA and 0.8 mg·ml−1 collagen with a low crosslinked density was optimal for myocardial cellular arrangement and alignment within the constructs. For the vascular fraction, the optimized formulation consisted of 5% GelMA, 0.8 mg·ml−1 collagen and 1 mg·ml−1 fibrinogen with a higher crosslinked density, which led to enhanced vascular cell connectivity. Printability assessment confirmed that the optimized bioinks could effectively fill the microfiber mesh while supporting cell viability (∼70%). Finally, the two bioinks were applied using a dual EBB system for the fabrication of a pre-vascular pathway with the shape of a left anterior descending artery within a myocardial construct, whereby the distinct cell populations could be visualized in their respective patterns up to D14. This research investigated the first step towards developing a thick engineered cardiac tissue construct in which a pre-vascularization pathway is fabricated within a myocardial construct.
KW - bioprinting
KW - cardiac tissue engineering
KW - converged biofabrication
KW - engineered heart tissue
KW - melt electrowriting
KW - myocardial tissue engineering
KW - pre-vascularization
UR - http://www.scopus.com/inward/record.url?scp=85164223135&partnerID=8YFLogxK
U2 - 10.1088/1758-5090/ace07f
DO - 10.1088/1758-5090/ace07f
M3 - Article
C2 - 37343567
AN - SCOPUS:85164223135
SN - 1758-5082
VL - 15
JO - Biofabrication
JF - Biofabrication
IS - 3
M1 - 035025
ER -