Non-Invasive Observation
If implants or tissue substitutes are being prepared on an industrial scale, non-invasive control is essential during manufacture and before use. This control accompanies the whole process of research and development. It starts with the observation and characterisation of the cell-implant interaction in vitro and ends with the first in vivo studies in the animal model or in clinical use.
Implant scaffolds are examined both before and after specific surface modification - ideally non-invasively and without contact. This is predominantly performed with optical imaging procedures, as these allow characterisation of the biocompatible matrices (scaffold) and surfaces with respect to colonisation by cells, together with the cell-implant interaction. Aside from straightforward measurements and biometrics, spectrophotometric and fluorescence methods are applied, particularly to characterise the interactions between the implant and scaffold and tissue or cells. For example, this can be used to demonstrate the efficacy of an implant modification.
A wide variety of techniques are used, including the scanning laser tomography procedure (SLOT) developed in the Hannover Laser Centre. This has been successfully employed to record bacterial colonisation on metal tooth implants in 3D over time. This procedure can be used to resolve the cells in relatively large metallic and non-metallic implants and scaffold structures. Optical coherence tomography (OCT) is an alternative procedure and this can be used in vivo. This has been used clinically in both ophthalmology and in cardiovascular medicine and allows the measurement of implants, both in vivo and in vitro.
Dye-free imaging with new contrast mechanisms is an important component of basic research in non-invasive observation. For example, non-linear imaging methods such as second and third harmonic microscopy (SHG and TGH) can be used to give dye-free high resolution images, thus allowing the non-invasive observation of cellular processes, initially in vitro. Several international research groups have achieved non-linear imaging on the skin in vivo and this allows tissue reactions to be studied in subcellular resolution - for example, on percutaneous implants. Another objective is to characterise the development of biofilms and infections with optical methods. Preliminary studies have already included non-linear laser microscopy in combination with scattered light imaging.
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