TY - JOUR
T1 - Synergizing bioprinting and 3D cell culture to enhance tissue formation in printed synthetic constructs
AU - Günther, Daniel
AU - Bergerbit, Cédric
AU - Marsee, Ary
AU - Vedaraman, Sitara
AU - Pueyo-Moliner, Alba
AU - Bastard, Céline
AU - Eelen, Guy
AU - Gerardo Nava, Jose Luis
AU - Dewerchin, Mieke
AU - Carmeliet, Peter
AU - Kramann, Rafael
AU - Schneeberger, Kerstin
AU - Spee, Bart
AU - De Laporte, Laura
N1 - Creative Commons Attribution license.
PY - 2025/1/24
Y1 - 2025/1/24
N2 - Bioprinting is currently the most promising method to biofabricate complex tissues in vitro with the potential to transform the future of organ transplantation and drug discovery. Efforts to create such tissues are, however, almost exclusively based on animal-derived materials, like gelatin methacryloyl, which have demonstrated efficacy in bioprinting of complex tissues. While these materials are already used in clinical applications, uncertainty about their safety still remains due to their animal origin. Alternatively, synthetic bioinks are developed that match the printability of natural bioinks but lack their biological complexity, and thereby often fail to support cell growth and facilitate tissue formation. Additionally, most synthetic materials do not meet the mechanical demands to bioprint stable constructs while providing a suitable environment for cells to grow, limiting the number of available bioinks. To bridge this gap and synergize bioprinting and 3D cell culture, we developed a PEG-based bioink system to promote the growth and spreading of cell spheroids that consist of human primary endothelial cells and fibroblasts. The 3D bioprinted centimeter-scale constructs have a high shape fidelity and accelerated softening to provide sufficient space for cells to grow. Adjusting the rate of degradability, induced by the integration of ester-functionalized crosslinkers in addition to protease cleavable crosslinkers into the hydrogel network, improves the growth of spheroids in larger printed hydrogel constructs containing an interconnected channel structure. The perfusable constructs enable extensive spheroid sprouting and the formation of a cellular network upon fusion of sprouts as initial steps towards tissue formation with the potential for clinical translation.
AB - Bioprinting is currently the most promising method to biofabricate complex tissues in vitro with the potential to transform the future of organ transplantation and drug discovery. Efforts to create such tissues are, however, almost exclusively based on animal-derived materials, like gelatin methacryloyl, which have demonstrated efficacy in bioprinting of complex tissues. While these materials are already used in clinical applications, uncertainty about their safety still remains due to their animal origin. Alternatively, synthetic bioinks are developed that match the printability of natural bioinks but lack their biological complexity, and thereby often fail to support cell growth and facilitate tissue formation. Additionally, most synthetic materials do not meet the mechanical demands to bioprint stable constructs while providing a suitable environment for cells to grow, limiting the number of available bioinks. To bridge this gap and synergize bioprinting and 3D cell culture, we developed a PEG-based bioink system to promote the growth and spreading of cell spheroids that consist of human primary endothelial cells and fibroblasts. The 3D bioprinted centimeter-scale constructs have a high shape fidelity and accelerated softening to provide sufficient space for cells to grow. Adjusting the rate of degradability, induced by the integration of ester-functionalized crosslinkers in addition to protease cleavable crosslinkers into the hydrogel network, improves the growth of spheroids in larger printed hydrogel constructs containing an interconnected channel structure. The perfusable constructs enable extensive spheroid sprouting and the formation of a cellular network upon fusion of sprouts as initial steps towards tissue formation with the potential for clinical translation.
U2 - 10.1088/1758-5090/adae37
DO - 10.1088/1758-5090/adae37
M3 - Article
C2 - 39854847
SN - 1758-5082
JO - Biofabrication
JF - Biofabrication
ER -