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

Alyssa A. Appel, Jeffery C. Larson, Bin Jiang, Zhong Zhong, Mark A. Anastasio, Eric M. Brey

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.