Low dose effect of bisphosphonates on hMSCs osteogenic response to titanium surface in vitro

N.R Alqhtani,N.J Logan,S Meghji,R Leeson,P.M Brett

doi:10.1016/j.bonr.2017.02.002

Abstract

Since the 1980s, titanium (Ti) implants have been routinely used to replace missing teeth. This success is mainly due to the good biocompatibility of Ti and the phenomenon of osseointegration, with very early events at implant placement being important in determining good osseointegration. However, enhancing implant performance with coatings such as hydroxyapatite (HA) and calcium phosphate has proved largely unsuccessful. Human mesenchymal stem cells (hMSCs) are the first osteogenic cells to colonise implant surfaces and offer a target for enhancing osseointegration. We previously reported that small doses of bisphosphonate (BP) may play an integral role in enhancing hMSC proliferation and osteogenic differentiation. The aim of this study is to investigate whether small doses of bisphosphonates enhance proliferation and osteogenic differentiation of hMSCs on Ti surfaces, to enhance bone osseointegration and to accelerate wound healing around the implant surface. Our data suggests that treating cells with small doses of BP (100nM & 10nM) induces significant hMSC stimulation of osteogenic markers including calcium, collagen type I and ALP compared to control group on titanium surfaces (P<0.05). In addition, cell proliferation and migration were significantly enhanced on titanium surfaces (P<0.05).

Highlights

In recent decades, titanium (Ti) implants have been successfully used to replace missing teeth
We have shown that various types of bisphosphonates promote osteogenic differentiation of Human mesenchymal stem cells (hMSCs) in vitro (Alqhtani et al, 2014)
We investigated whether low doses of BPs enhanced proliferation and osteogenic differentiation of hMSCs on Ti surfaces. hMSCs were used as they are the first cells to colonise implant surfaces and offer a target for enhancing osseointegration (Davies, 2003)

Summary

Introduction

Titanium (Ti) implants have been successfully used to replace missing teeth. This success is mainly due to the good biocompatibility of Ti and the phenomenon of osseointegration. Formation of fibrous tissue around the implant will lead to the clinical failure of the implant, whereas formation of new bone on the implant surface without interfering connective tissue is the desired outcome (Baas et al, 2012). It has been reported that optimal surface roughness can lead to effective osseointegration (Halldin et al, 2014). This effect was due to increased osteoblast proliferation, differentiation and matrix protein production, e.g. collagen type I. Surface hydrophilicity enhances cell interaction and adhesion to dental implants (Zhao et al, 2005, Logan et al, 2014a)

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