Molecular biointerface characterisation for an implanted medical device using cryogenic orbitrap secondary ion mass spectrometry (Cryo-OrbiSIMS)

Abstract

Despite their wide adoption, implanted medical device failures due to FBR remain significant and this process is poorly understood. Silicone rubber is a commonly employed material for implants, so here a poly(dimethyl siloxane) catheter is considered. Cryo-OrbiSIMS has for the first time been evaluated for characterisation of the biological deposition on implanted medical devices to expand our molecular biointerfacial description of the foreign body reaction (FBR) cascade. We remove subcutaneously implanted tube sections after 1 and 28 days in mice. Time-of-flight (ToF) SIMS was used for imaging, whilst OrbiSIMS analysis was used on the same instrument to characterise the metabolites in the biointerface at the surface of the explanted samples. Molecular formula predictor (MFP) peak assignments were coupled with both the machine learning logistic regression analysis approach and statistical comparisons to decipher changes in biomolecular makeup on the catheter surface. The analysis reveals elevated levels of sugars and itaconate were observed at 1 day while markers for inflammation such as urate, the common saturated fatty acids, myristic acid ( FA 14:0) and palmitic acid (FA 16:0) were higher on the catheter surfaces after 28 days of implantation. Analysis of the molecular depth profiles of the biointerface formed after 28 days of implantation reveals two distinct layers of biomolecule mixtures, where the layer next to the surface of the catheter is enriched in lipids while the area proximal to the collagenous capsule and host cell layer revealed by histology is dominated by fatty acids, amino acids from proteins and nucleic acid bases from RNA and DNA. The proteins and oligonucleotides are thought to originate from the cells whilst we postulate that the fatty acids are the original molecules deposited on the polymer device upon implantation. After only 1 day of implantation, few lipids are dominant, specifically the oxidised glycerophosphoglycerol PG (39:1;O) and the unsaturated fatty acid, FA 18:2 which are also found at the polymer surface after depth profiling through the biointerface of the 28-day implant, suggesting their importance in in the initial implant recognition. This is consistent with literature correlating oxidised lipids with inflammation. The information gained contributes to understanding the host response to implanted biomaterials to aid the design medical devices with reduced FBR.