Behavior of bone cells in contact with magnesium implant material

Abstract

Magnesium-based implants exhibit several advantages, such as biodegradability and possible osteoinductive properties. Whether the degradation may induce cell typespecific changes in metabolism still remains unclear. To examine the osteoinductivity mechanisms, the reaction of bone-derived cells (MG63, U2OS, SaoS2, and primary human osteoblasts (OB)) to magnesium (Mg) was determined. Mg-based extracts were used to mimic more realistic Mg degradation conditions. Moreover, the influence of cells having direct contact with the degrading Mg metal was investigated. In exposure to extracts and in direct contact, the cells decreased pH and osmolality due to metabolic activity. Proliferating cells showed no significant reaction to extracts, whereas differentiating cells were negatively influenced. In contrast to extract exposure, where cell size increased, in direct contact to magnesium, cell size was stable or even decreased. The amount of focal adhesions decreased over time on all materials. Genes involved in bone formation were significantly upregulated, especially for primary human osteoblasts. Some osteoinductive indicators were observed for OB: (i) an increased cell count after extract addition indicated a higher proliferation potential; (ii) increased cell sizes after extract supplementation in combination with augmented adhesion behavior of these cells suggest an early switch to differentiation; and (iii) bone-inducing gene expression patterns were determined for all analyzed conditions. The results from the cell lines were inhomogeneous and showed no specific stimulus of Mg. The comparison of the different cell types showed that primary cells of the investigated tissue should be used as an in vitro model if Mg is analyzed.

Mg-corrosion, hydroxyapatite, and bone healing

“…Similar in vitro systems have been used by others. 6,7,21 The results of XPS-analysis of Mg, MgO, and MgCO 3 after incubation for 72 h in tissue culture medium are shown in Fig. 5.…”

Magnesium alloys: A stony pathway from intensive research to clinical reality. Different test methods and approval‐related considerations

“…This dynamic tissue‐implant interface is of special interest when evaluating biocompatibility, as here the cells or tissues come into direct contact with the material or its degradation products. In addition, changes in physiological parameters, such as pH, ion concentrations and so forth, may trigger unwanted physiological reactions …”

“…21,[32][33][34][35] Notably, magnesium alloy extracts increase the pH of medium in which they are incubated; they also release potentially toxic ions and increase the osmolality. L929 cells can balance extracellular pH and osmolality to a certain extent 36 ; however, the high osmolality of magnesium alloy extracts can cause hyperosmotic shock in the first hours after the growth medium is replaced with extract. 37 Osmolality >500 mOsm kg 21 causes apoptosis, 38 and lower values might impact cell viability.…”

“…In addition, changes in physiological parameters, such as pH, ion concentrations and so forth, may trigger unwanted physiological reactions. 36,70,71 The crucial, but very fragile, tissue implant interface of biodegradable implants is a unique challenge for histological analysis, and the situation becomes even more challenging, when the surrounding tissue is not soft, such as a stented artery, but a hard tissue like bone.…”

Cellulose acetate membranes functionalized with resveratrol by covalent immobilization for improved osseointegration

“…This natural function of osteoblasts might be influenced by the presence of a degradable implant [36] [39]. Recent investigations have shown that magnesium (Mg) itself has the capacity to stimulate the osteoblasts and to induce osteoinductive properties [37][38][39][40] [40][41][42][43]. However, the rapid degradation rate of Mg remains a critical challenge.…”