Microsphere-Based Strategies for Bone Tissue Engineering

Microsphere-based approaches in bone tissue engineering exploit spherical particles, typically in the range of 50–500 µm, to deliver cells, growth factors and bioactive molecules in a controlled and spatially defined manner. These platforms may be fabricated from polymers (natural or synthetic), ceramics or composites, with tailored porosity, degradation kinetics and surface chemistry. By enabling minimally invasive administration, microspheres support localised osteogenic differentiation, vascular ingrowth and extracellular matrix deposition. Strategies include loading with osteoinductive peptides or growth factors, surface functionalisation to enhance cell adhesion, and fabrication of hierarchical scaffolds through bottom-up assembly of particle modules. Gradient-loaded microspheres mimic the osteochondral interface, while injectable composites combine microspheres with hydrogels to improve handling and conformability to irregular defects. Collectively, these approaches aim to restore bone continuity and function by orchestrating cell recruitment, angiogenesis and matrix mineralisation in situ.

Research from Nature Portfolio

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Research from all publishers

Silk fibroin/gelatin microcarriers have been shown to support mesenchymal stem cell adhesion and osteogenic differentiation under dynamic culture. By blending Bombyx mori‐derived silk fibroin with gelatin in defined ratios, reproducible microcarriers were produced via flow-focusing and assessed for mechanical stiffness and cell compatibility. Under osteogenic conditions, cells on these carriers exhibited alkaline phosphatase activity and mineral deposition, highlighting their utility as injectable building blocks for bone constructs.

Porous polyetheretherketone (PEEK) microcarriers coated with cell-derived mineralised extracellular matrix combine the mechanical robustness of PEEK with a bioactive surface. A wet-chemistry hydroxylation step generated interconnecting pores that facilitated protein adsorption and cell infiltration. Repeated cycles of recellularisation and decellularisation deposited an osteoconductive matrix, which enhanced proliferation and osteogenesis of human mesenchymal stem cells. In a rat calvarial defect model, these carriers accelerated bone repair, demonstrating translational potential.

Photocurable acrylate high-internal-phase emulsion (HIPE) porous microspheres have been explored as injectable bone fillers supporting both angiogenesis and osteogenesis. Fabricated via microfluidic or stirred-tank emulsion methods, these spheres allowed human embryonic stem cell-derived mesenchymal progenitor cells to migrate into surface pores. In vitro, differentiated osteoblasts deposited collagen and calcium, while in vivo chorioallantoic membrane assays revealed enhanced vascularisation around pre-seeded microspheres, emphasising the importance of pore architecture in promoting rapid defect perfusion and subsequent bone formation.

Microsphere-Based Strategies for Bone Tissue Engineering publication trend

The graph below shows the total number of articles in microsphere-based strategies for bone tissue engineering across all publications each year (not limited to Nature Index journals).

Technical terms

Microsphere: A spherical particle, typically 50–500 µm in diameter, used as a carrier for cells, drugs or bioactive agents in tissue engineering.

Microcarrier: A subtype of microsphere designed to support cell adhesion and expansion in three-dimensional culture systems.

Osteogenesis: The process of new bone formation involving the differentiation of progenitor cells into osteoblasts and subsequent mineralised matrix deposition.

Angiogenesis: The formation of new blood vessels from pre-existing vasculature, critical for nutrient delivery and integration of engineered constructs.

Extracellular matrix (ECM): The complex network of proteins and polysaccharides surrounding cells, providing structural support and regulatory cues for tissue formation.

References

1. Elastic porous microspheres/extracellular matrix hydrogel injectable composites releasing dual bio-factors enable tissue regeneration. Nature Communications (2024).
2. Silk fibroin/gelatin microcarriers as scaffolds for bone tissue engineering. Materials Science and Engineering C (2019).
3. Porous polyetheretherketone microcarriers fabricated via hydroxylation together with cell-derived mineralized extracellular matrix coatings promote cell expansion and bone regeneration. Regenerative Biomaterials (2021).
4. Porous microspheres support mesenchymal progenitor cell ingrowth and stimulate angiogenesis. APL Bioengineering (2018).
5. Microsphere-Based Scaffolds Carrying Opposing Gradients of Chondroitin Sulfate and Tricalcium Phosphate. Frontiers in Bioengineering and Biotechnology (2015).
6. Modular Strategies to Build Cell-Free and Cell-Laden Scaffolds towards Bioengineered Tissues and Organs. Journal of Clinical Medicine (2019).