Bone response is one of the key determining factors in the overall success of biomaterials intended for bone regeneration and osseointegration. Understanding the formation of bone at an implant surface may lead to the improved design of biomaterials for the future. However, due to the inhomogeneity of bone tissue at an interface, two-dimensional images often lack detail on the interfacial complexity. Furthermore, the increasing use of nanotechnology in the design and production of biomaterials demands characterization techniques on a similar nano length scale.
While current analysis methods, such as X-ray tomography, transmission electron microscopy, focused ion beam microscopy and scanning electron microscopy, provide a basis for analysing biomaterials and biointerfaces, they are incapable of doing so with both nanometre resolution and three-dimensional clarity. In contrast, electron tomography may be used to characterize the three-dimensional structure of biomaterials and their interfaces to bone with nanometre resolution.
In this work, hydroxyapatite scaffolds, and laser-modified titanium and Ti6Al4V implants were studied in contact with human or rabbit bone. Z-contrast electron tomography revealed that the orientation of collagen in bone apposing hydroxyapatite, titanium and Ti6Al4V implants is consistently parallel to the implant surface, where the bioactive layer that precipitates on HA is oriented perpendicular to the implant surface. With this method, complete three-dimensional nanoscale osseointegration of titanium-based implants was also established.
The extension of this technique from interfacial analyses to the design of biomaterials provided an understanding of the pore structure of mesoporous titania. In further investigations, the open three-dimensional pore network, as revealed by electron tomography, showed promise as a coating that improves implant osseointegration and enables site-specific drug-delivery from an implant surface.
In summary, it was demonstrated that two-dimensional characterization techniques were insufficient for the investigation of nanostructured biomaterials, as well as their interfaces to bone. Visualizing biointerfaces and biomaterials with nanometre precision in three-dimensions can expose new fundamental information on materials properties and bone response, enabling better design of biomaterials for the future.
|2012||Alexander B, Daulton TL, Genin GM, Lipner J, Pasteris JD, Wopenka B, Thomopoulos S. The nanometre-scale physiology of bone: steric modelling and scanning transmission electron microscopy of collagen-mineral structure. J R Soc Interface. August 7, 2012;9(73):1774-1786.|
|2011||Grandfield K, Palmquist A, Gonçalves S, Taylor A, Taylor M, Emanuelsson L, Thomsen P, Engqvist H. Free form fabricated features on CoCr implants with and without hydroxyapatite coating in vivo: a comparative study of bone contact and bone growth induction. J Mater Sci Mater Med. April 2011;22(4):899-906.|
|2012||Grandfield K, Engqvist H. Focused ion beam in the study of biomaterials and biological matter. Adv Mater Sci Eng. 2012;2012:841961.|
|1996||Landis WJ, Hodgens KJ, Arena J, Song MJ, McEwen BF. Structural relations between collagen and mineral in bone as determined by high voltage electron microscopic tomography. Microsc Res Tech. 1996;33(2):192-202.|
|2012||Grandfield K, Palmquist A, Ericson F, Malmström J, Emanuelsson L, Slotte C, Adolfsson E, Botton GA, Thomsen P, Engqvist H. Bone response to free‐form fabricated hydroxyapatite and zirconia scaffolds: a transmission electron microscopy study in the human maxilla. Clin Implant Dent Relat Res. June 2012;14(3):461-469.|
|1992||Weiner S, Traub W. Bone structure: from ȧngstroms to microns. FASEB J. February 1992;6(3):879-885.|