Feasibility of diffuse Raman spectroscopy to detect in-vivo molecular changes in the tissue induced by subcutaneous implants

Biomaterials are being designed for a broad range of medical applications, but regardless of their endpoint use, they trigger host immune responses, also known as foreign body responses (FBR). This study investigates the feasibility of using diffuse Raman spectroscopy (DRS) to detect <i>in-vivo</i> molecular changes in subcutaneous tissue situated immediately below the dermis. A mouse model of FBR after subcutaneous implantation of woven polyethylene terephthalate (PET) fibres is used to investigate this approach. Numerical modelling of light propagation in tissue is used to optimise the DRS instrument to detect Raman signals related to FBR-induced collagen deposition in tissue surrounding the PET fibres. Post-mortem <i>in-situ</i> measurements on mice (day 14, 21 and 28 post-implantation) showed that the intensity of the 930 cm^-1 Raman band, corresponding to collagen, correlates with the level of FBR observed by histology. The optimised DRS instrument allows the acquisition of <i>in-vivo</i> spectra from on mice under anaesthesia (day 7 and 28 post-implantation). Spectra from live mice (<i>in-vivo</i>) show a similar correlation between the intensity of the 930 cm^-1 collagen Raman band with the level of FBR, in agreement with the histology assessment of the skin. These results demonstrate the feasibility of performing <i>in-vivo</i> DRS measurements on a mouse model to detect molecular changes caused by FBR in the subcutaneous region below the skin. Such measurements can help the design of new biomaterials since it would enable longitudinal measurements of FBR on an individual animal rather the sacrificing animals for histology at specific time endpoints. Furthermore, it is amenable to development for monitoring FBR of implants clinically.