Human bone marrow-derived mesenchymal stem cells and osteoblast differentiation on titanium with surface-grafted chitosan and immobilized bone morphogenetic protein-2

Abstract

Circulating progenitor cells are known to home to various organs to repair injured tissues or to routinely replace old cells and maintain tissue integrity. Similarly, circulating progenitor bone cells can possibly home to a bone implant, differentiate, and eventually osteointegrate with the prosthesis. Osteointegration of bone cells with the prosthesis can help to reduce the risk of implant failure due to constant movement between bone tissue and implant surface. In this study, we aim to investigate if immobilized bone morphogenetic protein-2 (BMP2) on chitosan-grafted titanium substrate (Ti-CS-BMP2) will enhance bone marrow-derived mesenchymal stem cell (BMMSC) adhesion onto the substrate surface and further induce their differentiation into osteoblasts. The results show that our Ti-CS-BMP2 substrate is able to retain adsorbed BMP2, and is capable of slow release of this growth factor. Despite the lesser number of BMMSCs initially attached onto the Ti-CS-BMP2 substrates and consequently the lower level of cell proliferation, Ti-CS-BMP2 cells had the highest level of ALP activity. RT-PCR results show that Ti-CS-BMP2 cells had a relatively higher level of transcription activity of Runx2, compared with that of bone cell-derived osteoblasts (BC-OB), an indication that the BMMSCs were actively differentiating into osteoblasts. Finally, alizarin red staining reveals the presence of calcium deposits in the differentiated cells. Hence our Ti-CS-BMP2 substrates possess an osteoconductive effect and can possibly be used to fabricate bone implants that can osteointegrate with host bone tissue.

Chitosan as a potential osteogenic factor compared with dexamethasone in cultured macaque dental pulp stromal cells

“…The data seem to contradict previous reports that demonstrate enhanced mineralization following treatment with chitosan (Ambre et al 2013;Lim et al 2009;Wang et al 2011). However, these studies have shown that human bone-marrowderived mesenchymal stromal cells (hBMSCs) secrete a higher calcium content in the mineral deposit when hBMSCs are cultured with a chitosan-hydroxyapatite composite scaffold.…”

“…The osteoconductive property of hydroxyapatite has been widely studied. Thus, the positive stimulation on mineralization might be related to the incorporation of chitosan with this osteoconductive material (Ambre et al 2013;Lim et al 2009;Wang et al 2011). Our results are partially consistent with the study reported by Guzmàn-Morales and colleagues (2009) concerning the osteogenic effect of chitosan in hBMSCs culture compared with that of dexamethasone.…”

Application of BCBB/BMP/bFGF Complex in Repairing Femoral Head Necrosis in Rabbit Models

“…Bone morphogenetic protein (BMP) and basic fibroblast growth factor (bFGF) have been well studied in recent years [6][7][8] . BMP can induce mesenchymal stem cells (MSCs) to differentiate into chondrocytes and osteoblasts 9,10) . The bFGF promotes the proliferation of differentiated MSCs, and it is also a powerful angiogenic growth factor 11) .…”

Acidic pH resistance of grafted chitosan on dental implant

“…However, the attachment, stability and bioactivity maintenance of chitosan coatings at implant surfaces under drastic environments such as the oral cavity have proven to be highly influenced by different factors such as pH value variations [15,16]. To improve the strength of the covalent adhesion bindings and consequently the immobilization of chitosan molecules on the Ti surfaces, organic coupling agents such as glutaraldehyde [17,18] or silanated intermediaries such as 3-aminopropyltriethoxysilane (APTES) [19,20] or triethoxysylilbutyraldehyde (TESBA) molecules [21] have been employed. Currently, a novel chemical functionalization of Ti surfaces by peptide bonds has provided greater mechanical and immobilization properties of chitosan coatings [22].…”