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The Strontium Ion Reprograms Monocyte Subsets via TRPM2 Channel Regulation to Enhance Osseointegration.
Congrui Zhao1,2, Antian Xu1,2, Jingyao Gong1,2
1Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Zhejiang Key Laboratory of Oral Biomedical, Hangzhou 310000, China.
Biomaterials Research
|November 26, 2025
Summary
Strontium-doped implants reprogram immune cells called monocytes, reducing inflammation and improving bone healing around implants. This material-based immune modulation enhances osseointegration by targeting the TRPM2-NLRP3 pathway.
Area of Science:
- Biomaterials Science
- Immunology
- Orthopedic Engineering
Background:
- Successful osseointegration requires early immune homeostasis at the biomaterial-tissue interface.
- Strontium (Sr)-modified biomaterials show promise for enhancing osseointegration, but their immunomodulatory effects on monocytes are unclear.
- Understanding Sr's impact on monocyte subsets is crucial for designing effective biomaterials.
Purpose of the Study:
- To investigate how localized strontium release from engineered implants reprograms monocyte subsets.
- To elucidate the underlying molecular mechanisms of Sr-mediated immunomodulation.
- To assess the impact of these changes on osseointegration and bone regeneration.
Main Methods:
- Engineered strontium-doped sandblasted, large-grit, and acid-etched (Sr-SLA) titanium implants.
- Single-cell RNA sequencing to analyze monocyte subset dynamics around implants.
- In vitro validation of strontium ion effects on monocyte inflammasome activation (TRPM2-NLRP3 axis) and cytokine profiles.
- In vivo studies assessing osseointegration with and without monocyte depletion.
Main Results:
- Sr-SLA implants created an anti-inflammatory microenvironment, promoting osseointegration.
- Sr-SLA suppressed pro-inflammatory classical monocytes (Ly6Chi) by inhibiting the TRPM2-Ca2+-NLRP3 inflammasome pathway.
- Sr-SLA promoted regenerative nonclassical monocytes (Ly6Clo), leading to a cytokine profile that enhanced bone marrow mesenchymal stromal cell osteogenic differentiation.
- Monocyte depletion significantly impaired osseointegration in vivo.
Conclusions:
- Sr-SLA implants effectively reprogram monocyte subsets via the TRPM2-Ca2+-NLRP3 axis, reducing inflammation and enhancing bone regeneration.
- This study links biomaterial properties to immune response and bone healing, identifying an engineerable target for immunomodulatory biomaterials.
- Monocytes play an indispensable role in implant-mediated bone regeneration.
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