abstract
Advancing biofabrication toward manufacturing living constructs with well-defined architectures and increasingly biologically relevant cell densities is highly desired to mimic the biofunctionality of native human tissues. The formulation of tissue-like, cell-dense inks for biofabrication remains, however, challenging at various levels of the bioprinting process. Promising advances have been made toward this goal, achieving relatively high cell densities that surpass those found in conventional platforms, pushing the current boundaries closer to achieving tissue-like cell densities. On this focus, herein the overarching challenges in the bioprocessing of cell-rich living inks into clinically grade engineered tissues are discussed, as well as the most recent advances in cell-rich living ink formulations and their processing technologies are highlighted. Additionally, an overview of the foreseen developments in the field is provided and critically discussed. Biofabrication of biomimetic architectures leveraging on cell-rich living inks matching human tissue cellular densities can lead to unprecedented advances in generating architectures with life-like features and biofunctionalities, thus moving far beyond conventional biofabricated constructs where biomaterial-to-cell ratios remain nonphysiologic. This review showcases recent advances in the design of cell-rich inks and discusses key challenges toward translation to mainstream clinical applications. image
keywords
SELF-ORGANIZATION; SPHEROIDS; TISSUES; SYSTEM; BIOMATERIALS; CONSTRUCTS
subject category
Chemistry; Science & Technology - Other Topics; Materials Science; Physics
authors
Almeida-Pinto, J; Moura, BS; Gaspar, VM; Mano, JF
our authors
Projects
Collaboratory for Emerging Technologies, CoLab (EMERGING TECHNOLOGIES)
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
acknowledgements
This work was developed within the scope of the Project CICECO - Aveiro Institute of Materials, (Grant Nos. UIDB/50011/2020, UIDP/50011/2020, and LA/P/0006/2020), financed by National funds through the FCT/MEC (PIDDAC). The support of the European Research Council for the project REBORN (Grant No. ERC-2019-ADG-883370) is acknowledged. The authors acknowledge the financial support by the Portuguese Foundation for Science and Technology (FCT) through an Assistant Researcher contract (Grant No. 2022.02106.CEECIND, V.M.G.), and through the doctoral grants (Grant No. 2023.04716.BD, J.A.-P. and Grant No. 2021.08331.BD, B.S.M.).

