title: Imaging of Hydrogel Microsphere Structure and Foreign Body Response Based on Endogenous X-Ray Phase Contrast.
abstract: Transplantation of functional islets encapsulated in stable biomaterials has the potential to cure Type I diabetes. However, the success of these materials requires the ability to quantitatively evaluate their stability. Imaging techniques that enable monitoring of biomaterial performance are critical to further development in the field. X-ray phase-contrast (XPC) imaging is an emerging class of X-ray techniques that have shown significant promise for imaging biomaterial and soft tissue structures. In this study, XPC imaging techniques are shown to enable three dimensional (3D) imaging and evaluation of islet volume, alginate hydrogel structure, and local soft tissue features ex vivo. Rat islets were encapsulated in sterile ultrapurified alginate systems produced using a high-throughput microfluidic system. The encapsulated islets were implanted in omentum pouches created in a rodent model of type 1 diabetes. Microbeads were imaged with XPC imaging before implantation and as whole tissue samples after explantation from the animals. XPC microcomputed tomography (μCT) was performed with systems using tube-based and synchrotron X-ray sources. Islets could be identified within alginate beads and the islet volume was quantified in the synchrotron-based μCT volumes. Omental adipose tissue could be distinguished from inflammatory regions resulting from implanted beads in harvested samples with both XPC imaging techniques. Individual beads and the local encapsulation response were observed and quantified using quantitative measurements, which showed good agreement with histology. The 3D structure of the microbeads could be characterized with XPC imaging and failed beads could also be identified. These results point to the substantial potential of XPC imaging as a tool for imaging biomaterials in small animal models and deliver a critical step toward in vivo imaging.
authors: 1 Department of Biomedical Engineering, Illinois Institute of Technology , Chicago, Illinois.|2 Research Services, Edward Hines Jr. VA Hospital , Chicago, Illinois.
authors: Alyssa A
authors: AA
authors: Appel
authors: 1 Department of Biomedical Engineering, Illinois Institute of Technology , Chicago, Illinois.
authors: Veronica
authors: V
authors: Ibarra
authors: 1 Department of Biomedical Engineering, Illinois Institute of Technology , Chicago, Illinois.
authors: Sami I
authors: SI
authors: Somo
authors: 1 Department of Biomedical Engineering, Illinois Institute of Technology , Chicago, Illinois.|2 Research Services, Edward Hines Jr. VA Hospital , Chicago, Illinois.
authors: Jeffery C
authors: JC
authors: Larson
authors: 3 Department of Biomedical Engineering, Washington University in St. Louis , St. Louis, Missouri.
authors: Alfred B
authors: AB
authors: Garson
authors: 3 Department of Biomedical Engineering, Washington University in St. Louis , St. Louis, Missouri.
authors: Huifeng
authors: H
authors: Guan
authors: 4 Wake Forest Institute of Regenerative Medicine , Winston-Salem, North Carolina.
authors: John Patrick
authors: JP
authors: McQuilling
authors: 5 National Synchrotron Light Source, Brookhaven National Laboratory , Upton, New York.
authors: Zhong
authors: Z
authors: Zhong
authors: 3 Department of Biomedical Engineering, Washington University in St. Louis , St. Louis, Missouri.
authors: Mark A
authors: MA
authors: Anastasio
authors: 4 Wake Forest Institute of Regenerative Medicine , Winston-Salem, North Carolina.
authors: Emmanuel C
authors: EC
authors: Opara
authors: 1 Department of Biomedical Engineering, Illinois Institute of Technology , Chicago, Illinois.|2 Research Services, Edward Hines Jr. VA Hospital , Chicago, Illinois.
authors: Eric M
authors: EM
authors: Brey
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D005547:Foreign Bodies / Q000503:physiopathology*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007515:Islets of Langerhans / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D008858:Microscopy, Phase-Contrast / Q000379:methods*; D008863:Microspheres; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D055114:X-Ray Microtomography
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020723:Glucuronic Acid
keywords: MicroCT; X-ray phase contrast; alginate hydrogel; analyzer-based imaging