Advancing Organ-on-Chip Models With a Sacrificial Granular Hydrogel Strategy for Enhanced Permeability and Biomimicry

Area of Science:

• Biomaterials Engineering
• Infectious Disease Modeling
• Organ-on-Chip Technology

Background:

• Infectious diseases like malaria and HIV utilize bone marrow (BM) for latent infections.
• Studying these infections in patients is challenging, necessitating advanced in vitro models.
• Current organ-on-chip (OoC) hydrogels may hinder pathogen migration due to small mesh sizes.

Purpose of the Study:

• To develop a novel porous hydrogel for BM-on-chip models.
• To enhance pathogen and cell migration within OoC environments.
• To create a more biomimetic 3D-microenvironment for studying infection dynamics.

Main Methods:

• Developed a "reversed" granular hydrogel strategy using sacrificial alginate microgels as porogens.
• Embedded alginate microgels in a fibrin-collagen precursor within a custom BM-on-chip.
• Utilized in situ enzymatic/chemical leaching to create interconnected microporosity in the hydrogel (pFIB-COL).

Main Results:

• The porous fibrin-collagen (pFIB-COL) hydrogel supported 3D cultures of key bone marrow cells.
• pFIB-COL demonstrated reduced flow resistance and enhanced particle/cell permeation compared to native hydrogels.
• Improved cell distribution and endothelial network formation were observed in the pFIB-COL model.

Conclusions:

• The developed porous hydrogel strategy effectively creates interconnected microporosity in OoC devices.
• This approach enhances cellular and particle transport, crucial for modeling infection.
• The versatile strategy offers a valuable tool for biomimetic 3D modeling of infections in OoC systems.