abstract
This study proposes a novel, versatile, and modular platform for constructing porous and heterogeneous microenvironments based on the embedding of liquefied-based compartments in hydrogel systems. Using a bottom-up approach, microgels carrying the necessary cargo components, including cells and microparticles, are combined with a hydrogel precursor to fabricate a hierarchical structured (HS) system. The HS system possesses three key features that can be fully independently controlled: I) liquefied pockets enabling free cellular mobility; II) surface modified microparticles facilitating 3D microtissue organization inside the liquefied pockets; III) at a larger scale, the pockets are jammed in the hydrogel, forming a macro-sized construct. After crosslinking, the embedded microgels undergo a liquefaction process, forming a porous structure that ensures high diffusion of small biomolecules and enables cells to move freely within their miniaturized compartmentalized volume. More importantly, this platform allows the creation of multimodular cellular microenvironments within a hydrogel with controlled macrostructures, while decoupling micro- and macroenvironments. As a proof of concept, the enhancement of cellular functions using the HS system by encapsulating human adipose-derived mesenchymal stem cells (hASCs) is successfully demonstrated. Finally, the potential application of this system as a hybrid bioink for bioprinting complex 3D structures is showcased.
keywords
MESENCHYMAL STEM-CELLS; SCAFFOLDS; MODULATORS; VINCULIN
subject category
Engineering; Science & Technology - Other Topics; Materials Science
authors
Ghasemzadeh-Hasankolaei, M; Correia, TR; Mano, JF
our authors
João Mano
Full professor
Maryam Ghasemzadeh Hasankolaei
PhD Student
Tiago Ruivo Correia
Junior ResearcherProjects
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
The authors acknowledge the financial support of the doctoral grant (SFRH/BD/147418/2019), the FCT project TETRISSUE (PTDC/BTM-MAT/3201/2020), and the European Research Council REBORN (ERC2021-AdG883370). This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020, and LA/P/0006/2020, financed by national funds through the FCT/MEC (PIDDAC).