Osteogenic differentiation of cultured rat and human bone marrow cells on the surface of zinc‐releasing calcium phosphate ceramics

Abstract

Rat and human bone marrow cells (BMCs) were cultured on a composite ceramic of zinc-containing beta-tricalcium phosphate and hydroxyapatite (ZnTCP/HAP) with a (Ca+Zn)/P molar ratio of 1.60 and varying zinc contents. After a 2-week culture of the BMCs in the presence of beta-glycerophosphate and dexamethasone, many macroscopic mineralized areas with high alkaline phosphatase (ALP) activity were seen on the ZnTCP/HAP ceramic disks. The ALP activity increased with increasing zinc content in the ceramics. The highest ALP activity was observed when the BMCs were cultured on the ceramics with 1.26 wt % zinc, and the ceramics released zinc ions at concentrations from 2.2 to 7.2 microg/mL into the culture medium. Zinc ions were incorporated into mineralized areas produced by BMCs. BMCs also were directly cultured onto the culture dish surface, and the addition of 100 microM of free ZnCl(2) (6.5 microg/mL) to the culture medium significantly increased the ALP activity of the BMCs relative to the culture medium without the ZnCl(2)addition. The maximum zinc concentration required to enhance mineralization was higher in human BMCs than in rat BMCs. The present study demonstrates the superiority of ZnTCP/HAP ceramics over TCP/HAP in supporting the osteogenic differentiation of BMCs, and thus these ceramics are safe and useful in clinical settings, such as for bone reconstructive surgery.

In vitro studies of osteoblasts response onto zinc aluminate ceramic films

“…The Ca/P composition ratio of the mineral-like tissue was 1.63 which corresponds well with the biological hydroxyapatite value (Figure 7b). These results show that mineralization was not affected by the ZnAl 2 O 4 composition of the films and the mineral deposition enhance was in concordance with previous studies of zinc-containing biomaterials that had shown an osteoconductive material for bone-related tissue engineering applications [40][41][42][43] .…”

Improving the bone forming ability of synthetic bone substitutes using trace element additions

“…These findings are in line with the finding of Ito et al, who observed that both rat and human bone marrow stromal cells (BMSc) cultured on zinc-containing BCP differentiated into osteoblast-like cells more than cells on zinc-free ceramics [135]. Elevated zinc released in the medium would potentially play an important role in cell differentiation since it has been reported that supplementing zinc in the medium significantly increases the osteogenic differentiation of both rat and human BMSc [198]. Thus, it is possible that blood/bone marrow stem cells homing to the implantation site due to the inflammatory foreign body reaction may have infiltrated the materials and then differentiated into osteoblasts due to elevated zinc released by the ceramics.…”

“…Since the osteogenic differentiation of mesenchymal stem cells can be promoted by trace elements in vitro [198,199], we hypothesise that their addition in calcium phosphate-based materials can result in inductive bone formation. As the incorporation of these elements will also change the physical parameters of the calcium phosphate material (e.g.…”

Concept and Development of Vector Ceramics for Bio-interface Engineering

“…82) An implant of the zincdoped calcium phosphate ceramics significantly raised the cortical bone apposition rates of the femora of osteoporosismodeled rats. 83), 84) The zincdoped calcium phosphate ceramics were not absorbed due to the suppressive effects of the released zinc ions to osteoclasts in the area directly contacting the bone tissues.…”