Live monitoring of foreign-body response in animals by diffuse Raman spectroscopy

Implantable medical devices are widely used in healthcare. However, foreign body response (FBR) can lead to chronic inflammation, tissue damage, and fibrosis, resulting in device rejection and failure. The standard method for evaluating FRB in animal models is histological assessment of ex-vivo skin tissue surrounding the implant. Because histology is an end point technique, understanding the time-dependent changes caused by FBR require a large number of animals to be sacrificed and each time point.

Spatially-offset Raman Spectroscopy (SORS) was shown to be able to probe deeper in tissue and measure detailed molecular information of skin and connective tissue in-vivo. Our recent studies using phantom samples and rat cadavers showed that SORS was able to detect differences in collagen concentrations similar to those involved in bone healing. We also showed that Raman spectroscopy can detect changes in ex-vivo skin tissue caused by inflammation. However, the current SORS probes have limited sensitivity levels when measuring the small changes in tissue, such as those involved in FBR.

In this proposal we will develop a portable device based on diffuse Raman spectroscopy (DRS) for in-vivo monitoring of FBR. We will use modelling of light propagation in tissue to maximise the spectral contrast between the regions adjacent to the implant and surrounding tissue. This will be achieved by increasing the number of the laser excitation and detection points and optimising their spatial configuration on the surface of skin. Based on the optimised configuration, we will build a portable device equipped with a fibre optic handheld probe matching the high-throughput spectrometer and CCD, which will be suitable for in-vivo measurements on animal models. The ability to follow FBR on the same animal will provide higher quality data at high temporal resolution while reducing the number of animals used in research.

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Project grant

Status

Pending start

Institution

University of Nottingham

Grant reference number

NC/W001179/1

Award date

Sep 2021 - Feb 2024

Grant amount

£506,474