Cell Sheet Engineering for Bone Regeneration

Cell sheet engineering is a scaffold-free tissue engineering strategy in which contiguous layers of cells are harvested with their native extracellular matrix intact, preserving cell–cell junctions and secreted matrix components. This approach has been adopted to accelerate bone repair by deploying sheets of osteogenic cells, often derived from mesenchymal stem cells, directly onto defect sites. By avoiding harsh enzymatic digestion, cell sheets maintain a biologically active matrix that fosters cell survival, differentiation and integration with host tissue. Multilayered constructs can be fashioned to achieve desired thickness and mechanical properties, and they can be combined with growth factor-laden gels or mineral particles to further promote bone formation. Co-culture with endothelial or perivascular cells enhances vascularisation, while genetic or biochemical preconditioning can upregulate osteogenic pathways. Advances in temperature-responsive surfaces and magnetic detachment methods now permit reproducible fabrication of uniform sheets. The global significance of this technology lies in its potential to simplify surgical procedures, reduce reliance on synthetic scaffolds and offer tailored therapies for craniofacial, load-bearing and complex segmental defects.

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Cell Sheet Engineering for Bone Regeneration publication trend

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

Technical terms

Cell sheet engineering: A scaffold-free technique for harvesting confluent cell layers along with their native extracellular matrix to form implantable tissue constructs.

Mesenchymal stem cells (MSCs): Multipotent stromal cells capable of differentiating into osteoblasts, chondrocytes and adipocytes, commonly used for bone regenerative therapies.

Extracellular matrix (ECM): A complex network of proteins and glycosaminoglycans secreted by cells, providing structural support and biochemical cues for tissue formation.

Osteoangiogenesis: The coordinated process of new bone formation and vascular growth, essential for the survival and integration of engineered bone constructs.

References

1. Application of mesenchymal stem cell sheet for regeneration of craniomaxillofacial bone defects. Stem Cell Research & Therapy (2023).
2. Extracellular Matrix Deposition Defines the Duration of Cell Sheet Assembly from Human Adipose-Derived MSC. International Journal of Molecular Sciences (2023).
3. A Concise Review on the Use of Mesenchymal Stem Cells in Cell Sheet‐Based Tissue Engineering with Special Emphasis on Bone Tissue Regeneration. Stem Cells International (2017).
4. Combining mesenchymal stem cell sheets with platelet-rich plasma gel/calcium phosphate particles: a novel strategy to promote bone regeneration. Stem Cell Research & Therapy (2015).
5. Perivascular-Like Cells Contribute to the Stability of the Vascular Network of Osteogenic Tissue Formed from Cell Sheet-Based Constructs. PLOS ONE (2012).
6. Cell Sheets of Co-cultured Endothelial Progenitor Cells and Mesenchymal Stromal Cells Promote Osseointegration in Irradiated Rat Bone. Scientific Reports (2017).