Human induced pluripotent stem cell-derived beating cardiac tissues on paper

Area of Science:

• Biomaterials Science
• Stem Cell Biology
• Tissue Engineering

Background:

• Growing interest in paper as a biomaterial scaffold for cell culture.
• Need for cost-effective and accessible platforms for stem cell research.

Purpose of the Study:

• To fabricate the first paper-based array for culturing, proliferating, and differentiating human induced pluripotent stem cells (hiPSCs).
• To create functional beating cardiac tissues on paper, termed "a beating heart on paper."
• To evaluate different paper types as substrates for stem cell applications.

Main Methods:

• Fabrication of a paper-based array by binding a polydimethylsiloxane (PDMS) mold with commercial paper substrates (print paper, chromatography paper, nitrocellulose membrane).
• Culture and proliferation of hiPSCs on paper substrates.
• Direct differentiation of hiPSCs into cardiac tissues and retinal pigment epithelium.
• Assessment of cell morphology, pluripotency, and functional activity of differentiated tissues.

Main Results:

• hiPSCs exhibited good growth, 3D-like morphology, and maintained pluripotency on paper substrates.
• Functional beating cardiac tissues were successfully generated on coated print paper and chromatography paper, beating for up to three months.
• hiPSCs differentiated into retinal pigment epithelium on nitrocellulose membrane, suggesting material properties influence differentiation pathways.
• Paper substrates demonstrated potential for supporting stem cell growth and differentiation.

Conclusions:

• Paper-based arrays offer a promising, low-cost, bioactive, and 3D in vitro platform for stem cell applications.
• This technology can be utilized for high-throughput drug testing at the tissue/organ level and for tissue engineering.
• Material properties and mechanical cues of paper substrates play a role in regulating stem cell differentiation.