Osteogenic biphasic calcium sulphate dihydrate/iron-modified α-tricalcium phosphate bone cement for spinal applications: In vivo study

Abstract

In this study, the biocompatibility and the osteogenic features of a new iron-modified α-tricalcium phosphate (IM/α-TCP) and calcium sulphate dihydrate (CSD) biphasic cement (IM/α-TCP/CSD-BC) have been investigated in terms of the in vivo cement resorption, bone tissue formation and host tissue response on sheep animal model. Histological evaluation performed on undecalcified cement–bone specimens assessed the in vivo behaviour. It has been shown that the new IM/α-TCP/CSD-BC has the ability to produce firm bone binding in vivo (i.e. bioactivity). Qualitative histology proved cement biocompatibility, osteoconduction and favourable resorption, mainly through a macrophage-mediated mechanism. The results showed that the new cements have biocompatible and osteogenic features of interest as possible cancellous bone replacement biomaterial for minimally invasive spinal surgery applications.

Introduction

Since the first calcium phosphate bone cement (CPBC) synthesized by Brown and Chow [1] many different formulations have been studied and have resulted in various commercial products (i.e. Norian SRS^©, Cementek^©, Biocement-D^©, α-BSM^©, BoneSource^© and/or Biopex^©) [2], [3] used in a wide range of clinical applications (bone fractures, bone tumours, osteoporosis and craniofacial affections) [4], [5], [6], [7], [8], mainly due to the similar bone-like apatite structure evolved during their setting [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], their high biocompatibility and their good osteointegration after being implanted in vivo [19], [20], [21], [22].

Despite these advantages, it is generally accepted that CPBCs need further improvements to broaden their potential clinical applications [23] due to the fact that apatitic (i.e. the end setting product being hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂; HA) and/or calcium-deficient hydroxyapatite (Ca₉HPO₄(PO₄)₅OH; CDHA) [24], [25], [26]) bone cements are so stable in vivo that bone cement’s resorption takes a long time, i.e. months to years [27], [28], [29], [30]. In order to accelerate new bone apposition and resorption of the cement implant, several authors have improved the macroporosity, i.e. more and larger pores, of apatitic bone cements in several ways [31], [32], [33], [34], [35], [36], [37]. Moreover, depending on the degree of crystallinity and porosity, CPBCs can be made to be more or less stable after implantation [20], [29], [38], [39], [40]. In this sense, our research group presented a new method [41] to improve the osteointegration of α-tricalcium phosphate (α-TCP)-based cements by the modification of the cement’s powder phase with different amounts of calcium sulphate dihydrate (CSD). The resulting hardening properties of the new biphasic cements were a combination of the progressive hardening due to the main α-TCP reactant and the progressive dissolution of the CSD phase, which render a porous material [41]. In fact, CSD (first implanted by Dreesmann [42]) has been of interest to many scientists, who have used it as a filler material and/or as a replacement for cancellous bone graft due to its widely proved biocompatibility and rapid resorption [43], [44], [45], [46], [47]. Bohner [48] has even shown that small amounts of CSD added to the liquid phase can have interesting effects on the cement setting reactions, suggesting a complex effect of its sulphate ions.

In addition to the above, it should be noted that CPBCs lack high mechanical strength, and this limits their applications to non-load-bearing situations [23]. Moreover, with the advent of minimally spinal invasive surgery techniques (vertebro- and kyphoplasty), it has been put forward that apatitic cements are difficult to inject into compression fractured osteoporotic vertebrae [23], [49], [50]. However, our research group has been working on new methods to improve the osteointegration [41], as well as the injectability and strength of apatitic bone cements [51], [52], by iron modification of the main reactives, which is of interest to spinal applications.

Thus, the present study is a combination of the ideas previously published by our research group [41], [51], [53] and, it adds new data for the whole comprehension of the in vivo behaviour of new iron-modified α-tricalcium phosphate (IM/α-TCP) and calcium sulphate dihydrate (CSD) biphasic cements (IM/α-TCP/CSD-BCs). Thus, the objective of this research was to investigate the biocompatibility features of the new IM/α-TCP/CSD-BCs and their bioactivity (in the sense of osteoconduction and resorption) after implantation in a sheep model.