Titanium Is a Highly Thrombogenic Biomaterial: Possible Implications for Osteogenesis

Abstract

SummaryTitanium has superior osteointegrating properties compared to other biomaterials. The mechanism for this is unknown. During the initial phase of bone implantation the biomaterial comes into direct contact with whole blood. In this study we use a newly developed in vitro chamber model to compare different commonly used biomaterials in contact with whole blood. These materials were selected with respect to their different osteointegrating properties in order to correlate these properties with the response to whole blood. In the presence of 3 IU/ml of heparin only titanium induced macroscopic clotting. This was reflected by the generation of thrombin-antithrombin which was much increased in blood in contact with titanium compared with steel and PVC. The coagulation activation caused by titanium was triggered by the intrinsic pathway because the generation of FXIIa-AT/C1 esterase inhibitor paralleled that of thrombin-antithrombin, and both thrombinantithrombin complex and FXIIa-AT/C1 esterase inhibitor generation were abrogated by corn trypsin inhibitor, which is a specific inhibitor of FXIIa. The binding of platelets was increased on the titanium surface compared to the other biomaterial surfaces and the state of platelet activation was much more pronounced as reflected by the levels of β-thromboglobulin and PDGF. This study indicates that titanium is unsuitable as a biomaterial in devices which are in direct contact with blood for a prolonged period. Furthermore, PDGF and other α-granule proteins e.g. TGF-β, are known to be potent promotors of osteogenesis which suggests that the pronounced thrombogenic properties of titanium might contribute to the good osteointegrating properties.

Alkali treatment of microrough titanium surfaces affects macrophage/monocyte adhesion, platelet activation and architecture of blood clot formation

“…Several in vitro studies have addressed the infl uence of topographical (Park et al, 2001;Di Iorio et al, 2005) and physicochemical surface properties (Nygren et al, 1997;Hong et al, 1999;Eriksson and Nygren, 2001;Hong et al, 2005;Arvidsson et al, 2007) of Ti surfaces Alkali treatment of microrough titanium surfaces on the activation of blood coagulation, the adhesion of blood cells or the adsorption of plasma proteins. These studies indicate that native Ti is intrinsically highly thrombogenic due to strong contact activation (Hong et al, 1998;Hong et al, 1999;Arvidsson et al, 2007). Furthermore, both topographical and physicochemical properties of the surfaces were reported to infl uence the activation of blood coagulation.…”

“…for bone fi xation might be directly influenced by the physicochemical properties of the implant surface (Gorbet and Sefton, 2004;Stanford, 2010). Titanium (Ti), which is currently considered as the material of choice for manufacturing of load-bearing endosseous implants, has been reported to be highly thrombogenic -being one of the reasons for the materials outstanding osseointegrative characteristics (Hong et al, 1999). Recently, Ti implants with superhydrophilic microrough surfaces have attracted much interest due to their superb osseointegrative potential (Schwarz et al, 2009).…”

Introductory Chapter: Multi-Aspect Bibliographic Analysis of the Synergy of Technical, Biological and Medical Sciences Concerning Materials and Technologies Used for Medical and Dental Implantable Devices

“…Titanium is a very thrombogenic material [240]. The biocompatibility, especially thrombocompatibility, of Ti can be enhanced by introducing alloy elements [325]. Some publications [326][327][328][329][330][331][332][333][334] provide limited information on the toxic activity of V as an alloy element in the Ti6Al4V alloy, because it was found that V could be regarded as a potentially toxic factor [335,336], which is, however, true only for a considerable concentration of V in a body, due to development of its undesired immunological response, when the freed V ions migrate from the material surface to a soft tissue, binding with proteins [337,338].…”

“…Some research on cells implies that Ti6Al4V exhibits high cytotoxicity [307][308][309][310][311]339]; there are reports that V may cause sterile abscesses, and Al may cause scarring, while Ti, Zr, Nb and Ta show good biocompatibility [340]. Some publications argue that a risk associated with an unfavourable effect of Ti alloys can be limited by replacing V, as in, e.g., Ti6Al4V alloy, by Nb, e.g., in Ti6Al7Nb alloy, which would show better properties, e.g., corrosion resistance and bioavailability [334,[341][342][343][344][345][346]. It was revealed, however, by direct comparison in the same conditions that differences between Nb and V in Ti alloys are not too high [334], and even that Ti6Al4V alloys exhibit better properties than Ti6Al7Nb alloy [334,[347][348][349], such as thrombocompatibility, more intensive antibacterial activity and resistance to colonisation of Gram-positive bacteria, although worse for colonisation of Gram-negative bacteria [334].…”

Implantateinheilung

“…Die direkt nach erfolgter Implantatinsertion objektivierbare Primärstabilität ist eine Funktion aus mechanischer Knochenqualität, Implantat-(schrauben-)geometrie und Eindrehmoment [20,21] [11,15,19,23]. So findet sich auf rauen (z.B.…”