X-ray Phase Contrast Allows Three Dimensional, Quantitative Imaging of Hydrogel Implants

Abstract

Three dimensional imaging techniques are needed for the evaluation and assessment of biomaterials used for tissue engineering and drug delivery applications. Hydrogels are a particularly popular class of materials for medical applications but are difficult to image in tissue using most available imaging modalities. Imaging techniques based on X-ray Phase Contrast (XPC) have shown promise for tissue engineering applications due to their ability to provide image contrast based on multiple X-ray properties. In this manuscript, we investigate the use of XPC for imaging a model hydrogel and soft tissue structure. Porous fibrin loaded poly(ethylene glycol) hydrogels were synthesized and implanted in a rodent subcutaneous model. Samples were explanted and imaged with an analyzer-based XPC technique and processed and stained for histology for comparison. Both hydrogel and soft tissues structures could be identified in XPC images. Structure in skeletal muscle adjacent could be visualized and invading fibrovascular tissue could be quantified. There were no differences between invading tissue measurements from XPC and the gold-standard histology. These results provide evidence of the significant potential of techniques based on XPC for 3D imaging of hydrogel structure and local tissue response.

Imaging of Hydrogel Microsphere Structure and Foreign Body Response Based on Endogenous X-Ray Phase Contrast

“…XPC imaging is a developing category of X-ray techniques that have shown significant potential for imaging biomaterial and soft tissue structures that are difficult to observe with other imaging modalities. Specifically, these techniques have been successful in observing hydrogels in tissue 30,31,35 and low-density scaffolds in water 46 and soft tissue. 33,34 The techniques enable highresolution, large volume imaging of these materials, without the need for exogenous contrast agents.…”

“…The ideal imaging technique would not require exogenous contrast and be nondestructive. X-ray phasecontrast (XPC) imaging is a class of X-ray-based techniques that enable imaging of biomaterial and soft tissue structures, [30][31][32][33][34][35] which are difficult to observe using other imaging modalities. These techniques enable high-resolution and large volume imaging of these samples in the absence of exogenous contrast agents.…”

In Vivo Tracking of Tissue Engineered Constructs

“…Consequently, CT has been extensively used in different bone TE applications [66,67,68,69]. The development of more sensitive techniques like micro-CT has allowed for the study of the morphology and 3D structure of different scaffold geometries in the sub-micron scale as well as the tracking of different cells incorporated into the scaffold structures [70,71,72,73,74,75,76]. These unique advantages have also allowed CT to be used in conjunction with new additive manufacturing techniques, such as 3D (bio)printing, for different implant-manufacturing purposes [66].…”

Advances in bioinks and in vivo imaging of biomaterials for CNS applications

“…During the first week after implantation, animals had daily micro CT scans, which clearly showed the presence of biomaterial in the abdomen. Likewise, Appel et al [110] showed that XPC CT application allows 3D visualization and quantification of hydrated soft tissues and PEG hydrogels in vivo, with no contrast agents. The XPC CT imaging enabled a clear distinction between surrounding tissue after transplantation and the hydrogel structure.…”