Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

In Vivo Analysis of the Immune Response to Strontium- and Copper-doped Bioglasses

Version 1 : Received: 22 May 2022 / Approved: 23 May 2022 / Online: 23 May 2022 (05:24:12 CEST)

How to cite: Alkildani, S.; Mandlule, A.; Radenković, M.; Najman, S.; Stojanovic, S.; Jung, O.; Ren, Y.; Cai, B.; Görke, O.; Schmidt, F.; Barbeck, M. In Vivo Analysis of the Immune Response to Strontium- and Copper-doped Bioglasses. Preprints 2022, 2022050286 (doi: 10.20944/preprints202205.0286.v1). Alkildani, S.; Mandlule, A.; Radenković, M.; Najman, S.; Stojanovic, S.; Jung, O.; Ren, Y.; Cai, B.; Görke, O.; Schmidt, F.; Barbeck, M. In Vivo Analysis of the Immune Response to Strontium- and Copper-doped Bioglasses. Preprints 2022, 2022050286 (doi: 10.20944/preprints202205.0286.v1).

Abstract

Bioglasses are highly adoptable bone substitute materials, which can be combined with so-called therapeutic ions. These ions have shown to influence underlying molecular processes of the bone regeneration cascade. Moreover, it is known that bone substitutes induce an immune reaction within their implantation area involving macrophages and their pro- and anti-inflammatory subtypes dependent on their chemical composition. However, only poor knowledge exists regarding the influence of therapeutic ions onto the immune reactions and the associated bone healing. Thus, the aim of this work was to investigate the influence of strontium- and copper-doped bioglasses on the induction of M1- and M2-macrophages as well as the implant bed vascularization. (2) Methods: For this study, two alkali glasses were produced on basis of ICIE-16 bioglass via the melt-quench route with the addition of 5 wt% copper or strontium (ICIE16-Cu and ICIE16-Sr). Pure ICIE16 and 45S5 bioglasses were used as control materials. The bioactivity (ion release), chemical composition and the surface pattern were investigated, as well as an in vivo experiment was performed using the subcutaneous implantation model in rats. (3) Results: SEM imaging showed different formations of hydroxyapatite on the surfaces of the bioglass systems after submersion in simulated body fluid. EDX analysis confirmed the doping process by showing the release kinetics. Copper-doped bioglass exhibited a higher ion release than strontium-doped bioglass. Copper induced both a low immune cell migration and triggered a low number of M1- and M2-macrophages but also of blood vessels. The strontium-containing bioactive glass induced higher numbers of M1-macrophages after 30 days. Both copper- and strontium-doped bioglasses induced comparable numbers of M2-macrophages as found in the control groups. (4) Conclusions: Bioglass doping with copper and strontium did not exhibit significant influence on the foreign body response or the implantation bed vascularization in vivo. However, the prepared bioglass systems seemed to be biocompatible.

Keywords

bioglass; ion release; hydroxyapatite deposition; bone tissue regeneration; macrophages; vascularization; copper doping; strontium doping; 45S5; ICIE16

Subject

MEDICINE & PHARMACOLOGY, Dentistry

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