Development and evaluation of biocompatible inks for the local measurement of oxygen using in vivo EPR

Abstract

In vivo EPR oximetry is a powerful minimally invasive method that allows the measurement of oxygen in tissues through the use of a paramagnetic probe. In the present study, we investigated new strategies for preparing biocompatible inks containing carbon black particles (Printex U), which could be used as oxygen sensors. The carbon black particles were dispersed in solutions of biocompatible polymers of carboxy methyl cellulose (CMC), hydroxypropyl methyl cellulose (HPMC) or polyvinyl pyrrolidone (PVP). A total of 12 polymers with different molecular weights were tested. A physico-chemical characterization of the inks was carried out to assess the sedimentation of the particles, the rheological behavior of these inks, and the relative diffusion of the inks. The preparations with CMC and PVP had the highest viscosity and stability. The presence of the polymers did not modify the calibration curves (EPR linewidth as a function of the pO 2 ) of the carbon black. In vivo, the oxygen sensors were stable for at least one month in muscles as the EPR linewidth remained fully sensitive to induced ischemia or carbogen challenge. The calibration curve was not modified after this period of implantation. A first study of biocompatibility was carried out in vitro (hemolysis and cytotoxicity assay) and in vivo (histological examination). No sign of toxicity was observed using these inks. These preparations are good candidates for future in vivo studies including clinical trials.

Repetitive Tissue pO2 Measurements by Electron Paramagnetic Resonance Oximetry: Current Status and Future Potential for Experimental and Clinical Studies

“…Results indicate that the SAR measured in our clinical setup is well below the established limits (53). We have initiated the clinical studies using India ink as an oximetry probe, which is sensitive to tissue pO 2 , is very stable in tissue, and already has been approved for use in human subjects (8,37,38,61). This ink is prepared using components that are already in use in various pharmaceutical preparations.…”

“…This ink is prepared using components that are already in use in various pharmaceutical preparations. The reproducibility of this ink and its sensitivity to oxygen has been thoroughly examined and is found to be very satisfactory (8).…”

“…These measurements are being performed using India ink as the oximetry probe (8,37,38,61). India ink is sensitive to changes in pO 2 , has a stable and predictable response to these changes, and is already used in the clinic as a fiducial marker for radiation therapy and to delineate lymphatics, etc., in surgical procedures.…”

Comparative Study on Effects of Silver and Resin Fragments Injected into Periodontal Tissues in Healthy (m + /m +) and Diabetic Model (db/db) Mice with Special Reference to Histopathological and Immunohistochemical Observation

“…CMC is known to be bioabsorbable for high molecular weight materials and has good biocompatibility; therefore, it has been used as a solvent or coupling material for in vivo studies of biomaterials (13,14) . The histopathological results indicated inflammatory cell infiltration around the precipitated fragments of both silver and resin, with hemorrhage and capillary dilatation/proliferation followed by the appearance of foamy macrophages and fibrosis.…”

Clinical applications of in vivo EPR: Rationale and initial results

“…The India ink used in these experiments is prepared under strictly controlled conditions with components that are already in use in various pharmaceutical preparations. The reproducibility of this ink and its sensitivity to oxygen in different batches has been thoroughly examined and is found to be very satisfactory [14]. The ink (20 q was injected under the first metatarsal head, the site of greatest risk for patients with petipheral vascular diseases, anda series of pO2 measurements were carried out over the last year (Fig.…”