Osteogenic potential of sol–gel bioactive glasses containing manganese

Abstract

We report that the release of manganese ions from bioactive glass provoked human mesenchymal stem cell (hMSC) differentiation down a bone pathway, whereas hMSCs exposed to the Mn-free glass did not differentiate. Bioactive glasses (BGs) are widely used for bone regeneration, and allow the incorporation of different ions with therapeutic properties into the glass network. Amongst the different ions with therapeutic benefits, manganese (Mn) has been shown to influence bone metabolism and activate human osteoblasts integrins, improving cell adhesion, proliferation and spreading. Mn has also been incorporated into bioceramics as a therapeutic ion for improved osteogenesis. Here, up to 4.4 mol% MnO was substituted for CaO in the 58S composition (60 mol% SiO2, 36 mol% CaO, 4 mol% P2O5) and its effects on the glass properties and capability to influence the osteogenic differentiation were evaluated. Mncontaining BGs with amorphous structure, high specific surface area and nanoporosity were obtained. The presence of Mn 2+ species was confirmed by X-ray photoelectron spectroscopy (XPS). Mn-containing BGs presented no cytotoxic effect on human mesenchymal stem cells (hMSCs) and enabled sustained ion release in culture medium. hMSCs osteogenic differentiation stimulation and influence on the mineralisation process was also confirmed through the alkaline phosphatase (ALP) activity, and expression of osteogenic differentiation markers, such as collagen type I, osteopontin and osteocalcin, which presented higher expression in the presence of Mn-containing samples compared to control. Mn incorporation offers great promise for obtaining glasses with superior properties for bone tissue regeneration.

Effect of manganese, zinc, and copper on the biological and osteogenic properties of mesoporous bioactive glass nanoparticles

“…In this context, Mn ions have been shown to upregulate osteogenic marker genes and to improve extracellular matrix (ECM) formation when added to cell culture settings 7,13‐17 . There are several other ions with distinct therapeutic activity, which are interesting for application in BTE such as zinc (Zn) and copper (Cu) 8,18 .…”

Essentiality of Manganese for Bone Health: An Overview and Update

“…12 That Mn can stimulate the growth of osteoblasts and bone regeneration has also emerged from in vitro studies on bioactive glass, in which it has been observed how the addition of Mn is able to promote, in cultures of human osteoblasts, the expression of alkaline phosphatase (ALP) and some bone morphogenetic proteins (BMPs), 13 and to stimulate the osteogenetic differentiation of human mesenchymal stem cells (hMSCs) and influence the mineralization process by increasing the expression of markers of osteogenetic differentiation, such as type I collagen, osteopontin and osteocalcin. 14…”

The impact of environmental and occupational exposures of manganese on pulmonary, hepatic, and renal functions

“…Manganese (Mn) is one of the most abundant transition metals in the earth's crust and is an essential trace element of the human body. Mn is involved in regulating metabolism of macromolecules (carbohydrates, lipids, and proteins), immune response, bone formation, free radical scavenging, and reproduction (Barrioni et al, 2019; Kehl‐Fie & Skaar, 2010; Lee et al, 2006; Li & Yang, 2018). This trace element also acts as an activator and cofactor of many enzymes, including transferases, hydrolases, and oxidoreductases (Crowley et al, 2000).…”