Bone regeneration in sheep model induced by strontium-containing mesoporous bioactive glasses
Javier Jiménez-Holguín1, Daniel Lozano2, Melchor Saiz-Pardo3
1Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
Biomaterials Advances
|January 5, 2025
Summary
Strontium-containing bioactive mesoporous glasses (Sr-MBGs) significantly enhance bone regeneration in sheep models. Sr-MBGs promote osteogenesis and angiogenesis, offering a promising strategy for critical bone defect repair.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Materials Chemistry
Background:
- Local delivery of therapeutic ions from bioactive mesoporous glasses (MBGs) is a key strategy for bone defect regeneration.
- Strontium (Sr2+) is a promising therapeutic ion incorporated into MBGs for enhanced bone healing.
- Understanding the in vivo effects of Sr-containing MBGs is crucial for clinical translation.
Purpose of the Study:
- To investigate the bone regeneration potential of Sr-containing MBGs in a large animal model.
- To evaluate the impact of Sr2+ incorporation on the osteogenic and angiogenic properties of MBGs.
- To elucidate the mechanisms underlying Sr2+-enhanced bone formation.
Main Methods:
- MBGs with varying SrO content (0, 2.5, 5 mol%) were synthesized using the evaporation induced self-assembly (EISA) method.
- In vitro studies assessed apatite formation, preosteoblast (MC3T3-E1) viability, ALP activity, and gene expression (Runx2, ALP, VEGF).
- In vivo studies involved implanting MBGs and Sr-MBGs into cavitary bone defects in sheep, followed by histomorphometrical analysis and immunohistochemistry.
Main Results:
- Sr-MBGs exhibited similar apatite-forming ability to Sr-free MBGs in simulated body fluid (SBF).
- In vitro, Sr2+ enhanced MC3T3-E1 cell ALP activity and gene expression of Runx2, ALP, and VEGF, without affecting viability.
- HUVEC cell proliferation and VEGF expression increased with Sr2+ content.
- In vivo, Sr-MBGs significantly increased ossification area (20% vs 7%) and newly formed trabeculae thickness (30 μm vs 15 μm) compared to MBGs.
- Histological analysis indicated transient osteoclastogenesis inhibition and increased osteogenesis-angiogenesis.
Conclusions:
- Sr-MBGs demonstrate superior osteoregenerating potential compared to Sr-free MBGs in a large animal model.
- The enhanced bone formation is attributed to Sr2+-mediated osteogenesis and angiogenesis, potentially via osteoclastogenesis inhibition.
- Sr-containing MBGs represent a promising biomaterial for the treatment of critical bone defects.
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