In VivoAnalysis of the Immune Response to Strontium- and Copper-doped Bioglass

Abstract

Background: Bioglass is a highly adoptable bone substitute material which can be combined with so-called therapeutic ions. However, knowledge is poor regarding the influence of therapeutic ions on immune reactions and associated bone healing. Thus, the aim of this work was to investigate the influence of strontium-and copper-doped bioglass on the induction of M1 and M2 macrophages, as well as vascularization. Materials and Methods: Two types of alkali glass were produced based on ICIE16 bioglass via the melt-quench method with the addition of 5 wt% copper or strontium . Pure ICIE16 and 45S5 bioglass were used as control materials. The ion release and chemical composition of the bioglass were investigated, and an in vivo experiment was subcutaneously performed on Sprague-Dawley rats. Results: Scanning electron microscopy revealed significant differences in the surface morphology of the bioglass materials. Energy dispersive X-ray spectroscopy confirmed the efficiency of the doping process by showing the ion-release kinetics. ICIE16-Cu exhibited a higher ion release than ICIE16-Sr. ICIE16-Cu induced low immune cell migration and triggered not only a low number of M1 and M2 macrophages but also of blood vessels. ICIE16-Sr induced higher numbers of M1 macrophages after 30 days. Both bioglass types induced numbers of M2 macrophages comparable with those found in the control groups. Conclusion: Bioglass doping with copper and strontium did not significantly influence the foreign body response nor vascularization of the implantation bed in vivo. However, all the studied bioglass materials seemed to be biocompatible.Bone substitute materials (BSMs) are a small group including biomaterials mainly based on natural or synthetic calcium phosphates and similar compounds (1). Bioactive glass is a specific subgroup which has been shown to be a good BSM due to its optimal bonding to newly formed bone tissue and due to the formation of a hydroxycarbonate apatite layer which supports bone regeneration (2). Since the invention of bioactive glass materials in the 1970s by Professor Larry L. Hench, with 45S5 ® bioglass being one of the first developed materials, much research has been conducted on bioactive glass (3). Silicate-based bioactive glass and glass ceramics, such as Perioglas ® (4) and Ceravital ® (5, 6), have been clinically used as BSMs for several decades. Nevertheless, 2149

A surface metal ion-modified 3D-printed Ti-6Al-4V implant with direct and immunoregulatory antibacterial and osteogenic activity

“…Frontiers in Bioengineering and Biotechnology frontiersin.org and strontium ions can be introduced into the implant materials to regulate the immune (Barbeck et al, 2022).…”

“…As an essential osteophilic trace element for the human body, strontium ions induce and maintain the anti-inflammatory microenvironment, which is conducive to inhibiting the inflammatory response and promoting tissue repair ( Cai et al, 2021 ; You et al, 2022 ). Therefore, copper and strontium ions can be introduced into the implant materials to regulate the immune ( Barbeck et al, 2022 ).…”

Influence of Strontium on the Biological Behavior of Bioactive Glasses for Bone Regeneration

“…Barbeck et al [9] prepared ICIE16 glass (48SiO 2 -6.6Na 2 O-32.9CaO-2.5P 2 O 5 -10K 2 O) doped with 5 wt% Sr 2+ using the melt quench method, and performed an in vivo experiment subcutaneously in Sprague-Dawley rats. Their results indicated that the ICIE16-Sr bioactive glass induced a greater number of M1 macrophages after 30 days and a few M2 macrophages comparable to those found in the control groups, which did not significantly influence the foreign body response or the vascularization of the implantation bed in vivo.…”

“…These materials stimulate bone gene expression and angiogenesis, promoting excellent osteosynthesis, bioavailability, biodegradability and cellular conductivity [7]. However, these materials have some disadvantages, such as a small processing window, promoting to crystallization during the production process and negatively influencing bioactivity [8,9]. Furthermore, the original BG composition contains a large amount of sodium [10], and so could lead to cell death [11].…”

Immunomodulatory Effects Mediated by Nano Amorphous Calcium Phosphate/Chitosan Oligosaccharide Lactate Coatings Decorated with Selenium on Titanium Implants

“…According to the International Organization for Standardization (ISO), medical devices/implants might be considered biocompatible if after implantation in soft tissue are found to have a thin fibrous capsule with little evidence of ongoing inflammatory reaction [32]. Consequently, the determination of biocompatibility of materials for potential application in humans is aimed at the histological examination of fibrous capsule thickness and the presence of inflammatory cells at various time points after subcutaneous implantation [33][34][35][36][37][38]. In 2021, a paper has been published that proposed to redefine the term biocompatibility in order to describe materials that lead to vascularized, reconstructive healing and functional tissue integration with little or no fibrosis [39].…”