high-spatial-resolution-chemical-imaging-implant-associated

High Spatial Resolution Chemical Imaging of Implant-Associated Infections with X-ray Excited Luminescence Chemical Imaging Through Tissue

Microbial infections associated with implantable medical devices are a major concern in fracture fixation failure. Early diagnosis of such infection will ...

Clemson University

Two terbium germanates have been synthesized via high-temperature and high-pressure hydrothermal synthesis with 20 M KOH as a mineralizer using TbO as a starting material. Tb(GeO)O(OH) crystallizes in trigonal space group R3̅, is built up of isolated GeO units, and contains a complex arrangement of terbium oxide polyhedra. KTbGeO is a terbium(4+) pyrogermanate that is isostructural with KZrGeO and displays a rare stable Tb oxidation state in the solid state.

One-Pot Hydrothermal Synthesis of Tb(GeO)O(OH) and KTbGeO: Preparation of a Stable Terbium(4+) Complex.

We describe a pH-indicating material that can be directly implanted or coated on orthopedic implant surfaces to provide high-spatial-resolution pH mapping through tissue by X-ray excited luminescence chemical imaging (XELCI). This is especially useful for detecting local pH changes during treatment of implant-associated infections. The material has two layers: an X-ray scintillator layer with GdOS:Eu in epoxy, which emits 620 and 700 nm light when irradiated with X-rays, and a pH indicator dye layer, which absorbs some of the 620 nm light in a pH-dependent fashion. To acquire each pixel in the image, a focused X-ray beam irradiates a small region of scintillators and the ratio of 620 to 700 nm light is acquired through the tissue. Scanning the X-ray beam across the implant surface generates high-spatial-resolution chemical measurements. Two associated challenges are (1) to make robust sensors that can be implanted in tissue to measure local chemical concentrations specifically for metal orthopedic implants and (2) to conformally coat the implant surface with scintillators and pH indicator dyes in order to make measurements over a large area. Previously, we have physically pressed or glued a pH-sensitive hydrogel sensor onto the surface of an implant, but this is impractical for imaging over large irregular device areas such as an orthopedic plate with holes and edges. Herein, we describe a chemically sensitive and biocompatible XELCI sensor material that can conformally coat the implant surface. A two-part commercial-grade epoxy resin was mixed with GdOS:Eu and adhered to the titanium surface. Sugar and salt particles were added to the surface of the epoxy as it cured to create a roughened surface and increase the surface area. On this roughened surface, a secondary layer of diacrylated polyethylene glycol (PEG) hydrogel, containing a pH sensitive dye, was polymerized. This combination of epoxy-PEG layers was found to adhere well to the metal implant unlike other previously tested polymer surfaces, which delaminated when exposed to water or humidity. The focused X-ray beam enabled 0.5 mm spatial resolution through 1 cm-thick tissue. The pH sensor-coated orthopedic plate was imaged with XELCI, through tissue, with different pH levels to acquire a calibration curve. The plates were also imaged through tissue, with a low pH region on one section due to growth of a  biofilm. A pH sensor-coated stainless-steel rod with two distinct pH regions was inserted in a rabbit tibia specimen, and the pH was imaged through both bone and soft tissue. These studies demonstrate the use of pH sensor-coated orthopedic plates and rods for mapping the local pH through tissue during biofilm formation by XELCI.

Conformal Coating of Orthopedic Plates with X-ray Scintillators and pH Indicators for X-ray Excited Luminescence Chemical Imaging through Tissue.

X-ray excited optical luminescence from nanophosphors can be used to selectively generate light in tissue for imaging and stimulating light-responsive materials and cells. Herein, we synthesized X-ray scintillating NaGdF:Eu and Tb nanophosphors  co-precipitate and hydrothermal methods, encapsulated with silica, functionalized with biotin, and characterized by X-ray excited optical luminescence spectroscopy and imaging. The nanophosphors synthesized by co-precipitate method were ∼90 and ∼106 nm in diameter, respectively, with hydrothermally synthesized particles showing the highest luminescence intensity. More importantly, we investigated the effect of thermal annealing/calcination on the X-ray excited luminescence spectra and intensity. At above 1000 °C, the luminescence intensity increased, but particles fused together. Coating with a 15 nm thick silica shell prevented particle fusion and enabled silane-based chemical functionalization, although luminescence decreased largely due to the increased mass of non-luminescent material. We observed an increase in luminesce intensity with temperature until at 400 °C. At above 600 °C, NaGdF:Eu@SiO converts to NaGdSiO:Eu, an X-ray scintillator brighter than annealed NPs at 400 °C and dimmer than NPs synthesized using the hydrothermal method. The particles generate light through tissue and can be selectively excited using a focused X-ray source for imaging and light generation applications. The particles also act as MRI contrast agents for multi-modal localization.

Article	Year
One-Pot Hydrothermal Synthesis of Tb(GeO)O(OH) and KTbGeO: Preparation of a Stable Terbium(4+) Complex. Inorganic chemistry\| PubMed ID: 28537716	2017
Conformal Coating of Orthopedic Plates with X-ray Scintillators and pH Indicators for X-ray Excited Luminescence Chemical Imaging through Tissue. ACS applied materials & interfaces\| PubMed ID: 33181017	2020
X-ray excited luminescence spectroscopy and imaging with NaGdF:Eu and Tb. RSC advances\| PubMed ID: 35496840	2021

Apeksha C. Rajamanthrilage

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