Stem Cell Applications in Bone Tissue Engineering

Bone tissue engineering harnesses the regenerative potential of stem cells to restore or replace damaged skeletal structures. Central to this endeavour are multipotent mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSCs), both of which can be directed towards osteogenic lineages. Combining these cells with biocompatible scaffolds—ranging from hydrogels to composite ceramics—provides a three-dimensional framework that supports cell adhesion, proliferation and differentiation. Recent advances emphasise the importance of vascularisation, immune modulation and the delivery of bioactive factors such as growth factors or extracellular vesicles to mimic native bone microenvironments. Clinical translation has been driven by improvements in scaffold design, scalable cell manufacturing under good manufacturing practice conditions and the demonstration of safety and efficacy in preclinical fracture and defect models. These integrated approaches hold promise for the treatment of non-unions, critical-sized defects and osteoporosis-related fractures.

Research from Nature Portfolio

Human iPSC-derived osteoblasts and osteoclasts have been co-cultured on hydroxyapatite-coated poly(lactic-co-glycolic acid)/poly(L-lactic acid) scaffolds to recreate the cellular crosstalk of bone remodelling. This work demonstrated that co-cultured constructs accelerate matrix deposition and resorption in vitro and form mature bone-like tissue upon subcutaneous implantation in rodent models. These findings underscore the significance of incorporating both bone-forming and bone-resorbing cell types within a defined biomaterial environment to achieve physiologically relevant tissue development and immunomodulatory balance.

Stem Cell Applications in Bone Tissue Engineering publication trend

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

Technical terms

Mesenchymal stem cell (MSC): A multipotent stromal cell capable of differentiating into bone, cartilage and fat lineages, with immunomodulatory properties.

Induced pluripotent stem cell (iPSC): A somatic cell reprogrammed to a pluripotent state, capable of generating all cell types including osteoblasts and osteoclasts.

Scaffold: A three-dimensional biomaterial structure that provides mechanical support and spatial cues for cell attachment, proliferation and differentiation.

Osteogenic differentiation: The process by which progenitor cells acquire the phenotype and function of osteoblasts, the bone-forming cells.

Extracellular vesicle: A membrane-bound nanoparticle released by cells that carries proteins, lipids and nucleic acids to mediate intercellular communication.

References

1. Human iPSC-derived osteoblasts and osteoclasts together promote bone regeneration in 3D biomaterials. Scientific Reports (2016).
2. Mesenchymal Stromal Cell-Based Bone Regeneration Therapies: From Cell Transplantation and Tissue Engineering to Therapeutic Secretomes and Extracellular Vesicles. Frontiers in Bioengineering and Biotechnology (2019).
3. Clinical Application of Bone Marrow Mesenchymal Stem/Stromal Cells to Repair Skeletal Tissue. International Journal of Molecular Sciences (2020).
4. Pre-clinical studies of bone regeneration with human bone marrow stromal cells and biphasic calcium phosphate. Stem Cell Research & Therapy (2014).
5. Immune Modulation by Transplanted Calcium Phosphate Biomaterials and Human Mesenchymal Stromal Cells in Bone Regeneration. Frontiers in Immunology (2019).
6. Use of Autologous Human mesenchymal Stromal Cell/Fibrin Clot Constructs in Upper Limb Non-Unions: Long-Term Assessment. PLOS ONE (2013).