Calcium phosphate surfaces promote osteogenic differentiation of mesenchymal stem cells

Abstract

Although studies in vivo revealed promising results in bone regeneration after implantation of scaffolds together with osteogenic progenitor cells, basic questions remain how material surfaces control the biology of mesenchymal stem cells (MSC). We used human MSC derived from bone marrow and studied the osteogenic differentiation on calcium phosphate surfaces. In osteogenic differentiation medium MSC differentiated to osteoblasts on hydroxyapatite and BONITmatrix®, a degradable xerogel composite, within 14 days. Cells revealed a higher alkaline phosphatase (ALP) activity and increased RNA expression of collagen I and osteocalcin using real-time RTPCR compared with cells on tissue culture plastic. To test whether material surface characteristics alone are able to stimulate osteogenic differentiation, MSC were cultured on the materials in expansion medium without soluble additives for osteogenic differentiation. Indeed, cells on calcium phosphate without osteogenic differentiation additives developed to osteoblasts as shown by increased ALP activity and expression of osteogenic genes, which was not the case on tissue culture plastic. Because we reasoned that the stimulating effect on osteogenesis by calcium phosphate surfaces depends on an altered cell–extracellular matrix interaction we studied the dynamic behaviour of focal adhesions using cells transfected with GFP labelled vinculin. On BONITmatrix®, an increased mobility of focal adhesions was observed compared with cells on tissue culture plastic. In conclusion, calcium phosphate surfaces are able to drive MSC to osteoblasts in the absence of osteogenic differentiation supplements in the medium. An altered dynamic behaviour of focal adhesions on calcium phosphate surfaces might be involved in the molecular mechanisms which promote osteogenic differentiation.

Cell-material interaction

“…These coatings are described to induce an increased bone-to-implant contact and are regarded as osteoinductive [65]. In vitro, several studies have shown that a calcium phosphate coated implant surface promotes osteogenic differentiation of mesenchymal stem cells, which implies a stimulating effect of calcium phosphate for the formation of new bone [66][67][68].…”

Nano-ceramic Composite Scaffolds for Bioreactor-based Bone Engineering

“…Calcium phosphate ceramics, especially HA, are bioactive materials capable of promoting osteogenesis of MSCs [14,47]. Substrate topography comprised of various microand nanofeatures influences cellular behavior [46].…”

Biomaterials Applicable for Alveolar Sockets Preservation: In Vivo and In Vitro Studies

“…Similar to the outcomes of other bone substitution materials like NanoBone ® and their influence on bone healing process (Gotz et al 2008), the expression of Runx2 gene was unaltered after application of BONITmatrix ® and OSSA NOVA. Otherwise BONITmatrix ® slightly increased the expression of the osteogenic transcription factor Runx2 in mesenchymal stem cells (Muller et al 2008). In addition, it was suggested that diverse forms of hydroxyapatite nanoparticles may differentially affect the osteoblast cell function as shown on gene and protein levels (Xu et al 2009).…”

“…Furthermore, Real-time RT-PCR analyses showed that the amount of the osteocalcin and Alpl mRNA was significantly increased after treatment with BONITmatrix ® . It was recently shown that mesenchymal stem cells differentiated to osteoblasts within 14 days on hydroxyapatite and BONITmatrix ® in expansion medium with and without osteogenic differentiation additives (Muller et al 2008). Cells revealed a higher Alpl activity and increased mRNA expression of osteocalcin and collagen 1 (Muller et al 2008).…”

“…It was recently shown that mesenchymal stem cells differentiated to osteoblasts within 14 days on hydroxyapatite and BONITmatrix ® in expansion medium with and without osteogenic differentiation additives (Muller et al 2008). Cells revealed a higher Alpl activity and increased mRNA expression of osteocalcin and collagen 1 (Muller et al 2008). Another bone graft material consisting of nanocrystalline hydroxyapatite embedded in a porous silica gel matrix, Nanobone ® was implanted in the mandible of minipigs.…”