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Effect of Sintering Temperature of Bioactive Glass Nanoceramics on the Hemolytic Activity and Oxidative Stress Biomarkers in Erythrocytes



The nature of the surface is critical in determining the biological activity of silica powders. A novel correlation between toxicity and surface properties of bioactive glass ceramics (BGCs) synthesized via the sol–gel method was attempted in this study.


The behavior of BGCs after their attachment to the surface of red blood cells (RBCs) was evaluated and their toxic effects were determined based on hemolysis, membrane injury via anti-phosphotyrosine immunoblot of Band 3, lipid peroxidation, potential to generate reactive oxygen species, and antioxidant enzyme production. In particular, three BGCs were synthesized and treated at three sintering temperatures (T1 = 835 °C, T2 = 1000 °C and T3 = 1100 °C) to investigate possible relation between surface charge or structure and hemolytic potential.


Their toxicity based on hemolysis was dose dependent, while BGC-T2 had the best hemocompatibility in compare with the other BGCs.No BGCs in dosages lower than 0.125 mg/mL could damage erythrocytes. On the other hand, all BGCs promoted the production of reactive oxygen species in certain concentrations, with the BGC-T2 producing the lowest ROS and increasing the glutathione levels in RBCs protecting their damage.


The results suggest that various factors such as size, a probable different proportion of surface silanols, a balanced mechanism between calcium and magnesium cellular uptake or the different crystalline nature may have contributed to this finding; however, future research is needed to clarify the underlying mechanisms.

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The authors would like to thank for their support MSc student Laura De Diego and Ph.D student Cristina D’Avino.

Conflict of Interest

Ioannis Tsamesid is declares that he has no conflicts of interest. Konstantina Kazeli declares that she has no conflicts of interest. Evgenia Lymperaki declares that she has no conflicts of interest. Georgia K. Pouroutzidou declares that she has no conflicts of interest. Ilias M. Oikonomou declares that he has no conflicts of interest. Philomela Komninou declares that she has no conflicts of interest. George Zachariadis declares that he has no conflicts of interest. Karine Reybier declares that she has no conflicts of interest. Antonella Pantaleo declares that she has no conflicts of interest. Eleana Kontonasaki declares that she has no conflicts of interest.

Ethical Standards

Patients, all adults, provided written, informed consent before entering the study. The study was conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki. Ethical approval to perform the present study was obtained from the Ethical committee of the ASL. 1-Sassari. No animal experiments were performed in this study.

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IT and KK designed and executed experiments, interpreted data, were primary contributors to the text and figures and writing of the manuscript. EK designed experiments, interpreted data, wrote and revised the manuscript. EL designed experiments, interpreted data and revised the manuscript. GP designed and executed experiments regarding the characterization of the BGCs. GZ performed ICP analysis. KR and AP designed experiments and revised the manuscript. FK and IMO performed TEM analysis. All the co-authors have made significant contributions to improve the manuscript.

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Correspondence to Ioannis Tsamesidis.

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Tsamesidis, I., Kazeli, K., Lymperaki, E. et al. Effect of Sintering Temperature of Bioactive Glass Nanoceramics on the Hemolytic Activity and Oxidative Stress Biomarkers in Erythrocytes. Cel. Mol. Bioeng. 13, 201–218 (2020).

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  • Bioactive glass–ceramic nanoparticles
  • Red blood cells
  • Hemolysis
  • ROS production