Bioinstructive Liquefied Pockets in Hierarchical Hydrogels and Bioinks

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Hydrogel Engineering

Background:

• Developing controlled microenvironments is crucial for understanding cellular behavior and applications in regenerative medicine.
• Existing methods often struggle to independently control micro- and macro-scale features within engineered tissues.

Purpose of the Study:

• To present a versatile and modular platform for fabricating hierarchical structured (HS) systems with tunable porous microenvironments.
• To demonstrate the independent control over cellular mobility, microtissue organization, and macro-scale construct formation.
• To validate the platform's ability to enhance cellular functions and its potential as a bioink.

Main Methods:

• A bottom-up approach combining microgels with hydrogel precursors to form HS systems.
• Utilizing liquefied-based compartments within a hydrogel matrix for cellular encapsulation and mobility.
• Employing surface-modified microparticles for 3D microtissue organization within liquefied pockets.
• Demonstrating proof-of-concept with human adipose-derived mesenchymal stem cells (hASCs).

Main Results:

• Successful fabrication of HS systems with independently controllable features: cellular mobility, microtissue organization, and macro-structure.
• Liquefaction of embedded microgels creates porous structures facilitating biomolecule diffusion and cell movement.
• Demonstrated enhancement of hASC functions within the HS system.
• Showcased the HS system as a hybrid bioink for bioprinting complex 3D structures.

Conclusions:

• The developed HS system offers a novel, versatile platform for creating complex, porous cellular microenvironments.
• This platform decouples micro- and macro-environmental controls, enabling precise engineering of cellular niches.
• The HS system holds significant potential for applications in regenerative medicine, drug screening, and advanced bioprinting.