Cell Sheet Engineering in Tissue Regeneration

Summary

Cell sheet engineering is a scaffold-free approach to tissue regeneration in which contiguous layers of cells, together with their native extracellular matrix, are cultured and harvested as intact sheets. By preserving cell–cell junctions and secreted matrix components, these sheets can be stacked or wrapped to form three-dimensional constructs with enhanced mechanical integrity and biological functionality. Key techniques for sheet detachment include thermoresponsive coatings that alter cell adhesion on temperature change, light-induced surfaces that trigger matrix release under specific wavelengths, and stimulus-responsive polymers that cleave or swell in response to chemical cues. This versatility has enabled applications in corneal repair, cardiac patch fabrication, periodontal regeneration and the repair of mucosal tissues. Ongoing efforts focus on improving vascularisation within multilayered constructs, tailoring sheet geometry for complex anatomy and integrating bioactive cues to guide cell differentiation. The global significance of this field lies in its potential to deliver off-the-shelf tissue constructs that integrate seamlessly with host tissues, reducing reliance on synthetic scaffolds and improving clinical outcomes.

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Cell Sheet Engineering in Tissue Regeneration publication trend

The graph below shows the total number of articles in cell sheet engineering in tissue regeneration across all publications each year (not limited to Nature Index journals).

Technical terms

Thermoresponsive polymer: A material that changes its surface properties in response to temperature, used to detach cell sheets by lowering or raising the temperature.

Extracellular matrix (ECM): The network of proteins and polysaccharides secreted by cells that provides structural support and biochemical signals within tissues.

Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen that can be harnessed to degrade or modify substrate coatings, enabling controlled cell sheet release.

Nanostructured polymer film: A surface engineered at the nanometre scale to present distinct adhesive and detachment domains for non-enzymatic harvesting of cell sheets.

References

  1. Strategy for Nonenzymatic Harvesting of Cells via Decoupling of Adhesive and Disjoining Domains of Nanostructured Stimulus-Responsive Polymer Films. ACS Applied Materials & Interfaces (2023).
  2. Recent Advances in ROS-Responsive Cell Sheet Techniques for Tissue Engineering. International Journal of Molecular Sciences (2019).
  3. Laminin‐521 Promotes Rat Bone Marrow Mesenchymal Stem Cell Sheet Formation on Light‐Induced Cell Sheet Technology. BioMed Research International (2017).
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