Bioreactor Design for Culturing Vascularized Engineered Tissue in Flow Conditions

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Tissue Engineering

Background:

• Congenital heart defect treatments often involve synthetic materials leading to scar tissue and reoperations.
• Previous rat studies showed prevascularized scaffolds integrate into heart tissue.
• Thicker scaffolds for human hearts require methods for cell seeding and maturation under physiological conditions.

Purpose of the Study:

• To develop a bioreactor system for perfusing and electrically stimulating thick, porous scaffolds for cardiac tissue engineering.
• To evaluate biocompatible polymers for induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM) viability.
• To assess cell infiltration and maturation within scaffolds under dynamic culture conditions.

Main Methods:

• A bioreactor system was designed for perfusing up to six 7mm porous scaffolds with tunable gravity-mediated flow and electrical stimulation.
• Three biocompatible polymers (MED610, Vero, FORMLAB) were tested for iPSC-CM viability.
• Scaffolds with endothelial cells and fibroblasts were cultured under static and flow conditions for up to 7 days, with cell infiltration quantified via immunofluorescence.

Main Results:

• MED610, Vero, and FORMLAB materials did not affect iPSC-CM viability; MED610 was selected for 3D printing.
• Bioreactor functions, including electrical field stimulation (0-5V) and physiological flow rates, were verified.
• Cell infiltration and structure within scaffolds were successfully evaluated after 2, 5, and 7 days of culture.

Conclusions:

• The developed gravity-mediated flow bioreactor is a viable platform for 3D cell culture.
• This system is specifically designed for perfusing vascularized tissue constructs with electrical stimulation for cardiac maturation.
• This technology holds potential for engineering cardiac tissues to treat congenital heart defects.