A Layer-by-Layer Single-Cell Coating Technique To Produce Injectable Beating Mini Heart Tissues via Microfluidics

Area of Science:

• Biomedical Engineering
• Stem Cell Biology
• Regenerative Medicine

Background:

• Human induced pluripotent stem cells (hiPSCs) offer an alternative to embryonic stem cells for regenerative therapies.
• The heart's limited regeneration capacity necessitates strategies for cardiac tissue repair after infarction.
• Injectable cell delivery systems are crucial for efficient regenerative cell transplantation.

Purpose of the Study:

• To develop an injectable microgel system for enhanced cardiac tissue regeneration.
• To improve the viability and function of encapsulated cardiomyocytes and fibroblasts.
• To create functional cardiac mini-tissues for transplantation therapies.

Main Methods:

• Coculture of hiPSC-derived cardiomyocytes (hiPSC-CM) and dermal fibroblasts encapsulated in PEG-based microgels using microfluidics.
• Microgel preparation via Michael-type addition with enzymatically degradable peptides and cell-adhesive modification.
• Layer-by-layer (LbL) deposition for extracellular matrix (ECM) coating on cell surfaces to enhance cell-cell interactions.

Main Results:

• Microgels successfully encapsulated hiPSC-CM and fibroblasts, forming injectable cardiac constructs.
• LbL coating significantly improved cell-cell interactions and cell viability.
• Encapsulated cardiomyocytes exhibited a 2-fold increase in beating strength (approx. 60 BPM) compared to non-coated cells.

Conclusions:

• The combination of microfluidics and LbL technology enables the fabrication of functional cardiac mini-tissues.
• This approach enhances cell viability and function, offering a promising strategy for cardiac cell transplantation.
• The developed injectable microgel system holds potential for improving cardiac tissue regeneration therapies.