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InVERT molding for scalable control of tissue microarchitecture
K R Stevens1, M D Ungrin, R E Schwartz
1Harvard-MIT Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nature Communications
|May 16, 2013
Summary
A new method enables precise microscale organization of multiple cell types in engineered tissues. Optimized tissue architecture improves cell function and survival in vivo, advancing tissue engineering for therapies.
Area of Science:
- Tissue Engineering
- Biomaterials Science
- Stem Cell Biology
Background:
- Complex tissues feature hierarchical organization of diverse cell types within distinct compartments.
- Current tissue fabrication methods limit the microscale organization of multiple cell types, hindering the development of physiologically relevant engineered tissues.
- Advanced tissue engineering strategies are needed to create complex tissues for research and therapeutic applications.
Purpose of the Study:
- To present a novel method, 'Intaglio-Void/Embed-Relief Topographic molding', for versatile microscale organization of multiple cell types.
- To investigate how cellular composition and compartmental architecture influence engineered hepatic tissue function.
- To assess the in vivo survival and function of architecturally optimized engineered tissues.
Main Methods:
- Development and application of the 'Intaglio-Void/Embed-Relief Topographic molding' technique.
- Incorporation of various cell types, including induced pluripotent stem cell-derived progeny and hepatocytes, within diverse extracellular matrices.
- Systematic modulation of cell placement, compartment microstructure, and cellular composition to engineer hepatic tissues.
Main Results:
- Demonstrated successful microscale organization of multiple cell types in engineered tissues of various sizes.
- Showcased that compartmental placement, microstructure, and cellular composition significantly modulate hepatic functions.
- Engineered tissues that sustained physiological function in vitro exhibited survival and function in mice for at least 4 weeks post-implantation.
Conclusions:
- The 'Intaglio-Void/Embed-Relief Topographic molding' method offers versatile control over microscale tissue architecture.
- Architectural optimization is critical for achieving and maintaining physiological function in engineered tissues.
- This technique holds promise for advancing in vitro, pre-clinical, and clinical applications in tissue engineering and regenerative medicine.