POL Scientific / JBM / Volume 13 / Issue 1 / DOI: 10.14440/jbm.0323
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RESEARCH ARTICLE

Dose-dependent immunomodulatory effects of silver-doped nanostructured bioglasses in calvarial bone repair

Gustavo Henrique Marques Ribeiro1† ,  Rafael Obata Trevisan1† ,  Malu Mateus Santo Obata1 ,  Chamberttan S. Desidério2 ,  Odival Seabra1 ,  Renata Margarida Etchebehere3 ,  Carlo José Freire Oliveira2 ,  Noelio Oliveira Dantas4 ,  Anielle Christine Almeida Silva5 ,  Hugo F. Perini2 ,  Marcos Vinicius da Silva2 ,  Sanívia Aparecida de Lima Pereira6,7 ,  Rodrigo César Rosa1*
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1 Department of Structural Biology, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais 38025-350, Brazil
2 Department of Microbiology, Immunology and Parasitology, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais 38025-350, Brazil
3 Department of Surgical Clinic, Institute of Health Sciences, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais 38025-350, Brazil
4 Department of Physical Sciences, Physics Institute, Federal University of Alagoas, Maceió, Alagoas 57072-900, Brazil
5 Department of Physical Sciences, Physics Institute, Federal University of Uberlândia, Uberlândia, Minas Gerais 38025-350, Brazil
6 Postgraduate Program in Dentistry, University of Uberaba, Uberaba, Minas Gerais 38055-500, Brazil
7 Center for Professional Education, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais 38025-350, Brazil
JBM 2026 , 13(1), e99010098; https://doi.org/10.14440/jbm.0323
Submitted: 7 October 2025 | Revised: 12 December 2025 | Accepted: 22 December 2025 | Published: 3 March 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Background: Silver-doped nanostructured bioglasses have emerged as promising biomaterials for bone repair due to their bioactivity and potential to modulate immune–inflammatory responses. Objective: To assess immune–inflammatory modulation by silver-doped nanostructured bioglasses during bone repair in rat calvarial defects. Methods: In this study, nanostructured bioglasses were synthesized using a melt-quench method with silicon dioxide, sodium carbonate, calcium carbonate, and phosphorus pentoxide as precursors, followed by the incorporation of silver(I) oxide at concentrations ranging from 0.25 to 1.50 wt%. Results: Structural characterization confirmed the amorphous nature of the materials and the homogeneous incorporation of silver (Ag), forming nanoscale features at the bioglass surface. Eighty male Wistar rats were subjected to critical-size calvarial defect surgery to evaluate tissue response, inflammatory modulation, and systemic safety after bioglass implantation. Histological analysis demonstrated limited residual material particles and predominantly mild inflammatory infiltrates across treated groups, while hepatic and renal tissues exhibited preserved histoarchitecture, confirming the absence of systemic toxicity. Systemic cytokine profiling revealed a concentration-dependent immunomodulatory effect. Pure bioglass (Ag-0.00) and high silver content (Ag-1.50) enhanced the production of anti-inflammatory cytokines interleukin-4 and interleukin-10, whereas intermediate Ag concentrations (Ag-0.50–0.75) selectively increased pro-inflammatory mediators, including tumor necrosis factor alpha and interferon gamma. These patterns suggest that Ag content influences the balance between immune activation and resolution phases during bone repair. Intermediate concentrations were associated with improved tissue organization and histological features compatible with early reparative processes, whereas higher concentrations favored a regulatory inflammatory profile compatible with later stages of healing. Conclusion: Overall, the findings demonstrate that Ag incorporation enables fine-tuned, dose-dependent modulation of immune–inflammatory responses while maintaining systemic biocompatibility, supporting the potential of Ag-doped nanostructured bioglasses as multifunctional candidates for bone repair applications.

Keywords
Immunomodulation
Osteoimmunology
Bioglass
Silver nanoparticles
Bone repair
Funding
This study was supported by the Minas Gerais Research Foundation (FAPEMIG) under grants RED-00224-23 (Minas Gerais Network of Translational Nanobioplatforms) and REDAPQ-03655-23 (MultiLab).
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Conflict of interest
The authors declare that they have no competing interests.
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Journal of Biological Methods, Electronic ISSN: 2326-9901 Print ISSN: TBA, Published by POL Scientific
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