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Proteomic insights into the immunomodulatory effects of Ca/Sr co-doped sol-gel coatings for titanium implants.

Iñaki García-Arnáez·Francisco Romero-Gavilán·Andreia Cerqueira·Fabio Savastano·Mikel Azkargorta·Félix Elortza·Julio Suay·Isabel Goñi·Mariló Gurruchaga
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Abstract

Ionic functionalization of biomaterial coatings has emerged as a powerful strategy to regulate early host responses at the implant interface. However, how combined Ca/Sr incorporation governs the adsorbed proteome and downstream immune signaling remains poorly understood. This study analyses, employing in vitro tests and proteomics, the effect of adding Sr and Ca to Si-based coatings designed to bioactivate Ti implants. Hybrid Si-based coatings were synthesized by the sol-gel route with a fixed Ca content (0.5 wt%) and increasing Sr contents (0.5, 1.0, 1.5 wt%), and their physicochemical properties, ion release kinetics, and hydrolytic stability were characterized. The coatings remained highly crosslinked despite Ca/Sr incorporation, whereas the highest Sr content increased hydrolytic degradation to around 70% after 56 days. Proteomic analysis identified 183 adsorbed proteins, of which 56 were differentially adsorbed on Ca/Sr-coatings, mainly associated with immune and coagulation pathways. In vitro, RAW 264.7 showed increased gene expression of TNF-α and TGF-β; with an enhanced TNF-α secretion by the addition of Ca and Sr. In parallel, MC3T3-E1 indicated that Ca/Sr-coatings were not cytotoxic and did not impair cell proliferation. However, ALP activity was reduced in the co-doped groups, indicating that the immunomodulatory effects induced by Ca/Sr incorporation were not accompanied by enhanced early osteogenic differentiation. The Ca/Sr combination induced alterations in the adsorption of immune-related proteins, which correlated with the in vitro findings. The deeper insight into how Ca/Sr mixtures modulate protein adsorption on biomaterial surfaces may be key to understanding the immunomodulatory capacity of these bioactive cations.

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AnimalsTitaniumStrontiumMiceCoated Materials, BiocompatibleProteomicsCalciumRAW 264.7 CellsCell ProliferationSurface PropertiesTumor Necrosis Factor-alphaImmunologic FactorsProstheses and ImplantsGelsBioinorganicsImmunomodulationTi implantsJournal Article

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Iñaki García-Arnáez, Francisco Romero-Gavilán, Andreia Cerqueira, Fabio Savastano, Mikel Azkargorta, Félix Elortza, Julio Suay, Isabel Goñi, Mariló Gurruchaga. 2026-07-16. Proteomic insights into the immunomodulatory effects of Ca/Sr co-doped sol-gel coatings for titanium implants.. https://doi.org/10.1016/j.colsurfb.2026.115991

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Journal Article resourceAnimals subjectCalcium subjectCell Proliferation subjectJournal Article subjectMice subjectProstheses and Implants subject

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