title: Longitudinal in vivo evaluation of bone regeneration by combined measurement of multi-pinhole SPECT and micro-CT for tissue engineering.
abstract: Over the last decades, great strides were made in the development of novel implants for the treatment of bone defects. The increasing versatility and complexity of these implant designs request for concurrent advances in means to assess in vivo the course of induced bone formation in preclinical models. Since its discovery, micro-computed tomography (micro-CT) has excelled as powerful high-resolution technique for non-invasive assessment of newly formed bone tissue. However, micro-CT fails to provide spatiotemporal information on biological processes ongoing during bone regeneration. Conversely, due to the versatile applicability and cost-effectiveness, single photon emission computed tomography (SPECT) would be an ideal technique for assessing such biological processes with high sensitivity and for nuclear imaging comparably high resolution (<1 mm). Herein, we employ modular designed poly(ethylene glycol)-based hydrogels that release bone morphogenetic protein to guide the healing of critical sized calvarial bone defects. By combined in vivo longitudinal multi-pinhole SPECT and micro-CT evaluations we determine the spatiotemporal course of bone formation and remodeling within this synthetic hydrogel implant. End point evaluations by high resolution micro-CT and histological evaluation confirm the value of this approach to follow and optimize bone-inducing biomaterials.
authors.affiliation: Laboratory for Cell and Tissue Engineering, Department of Obstetrics, University Hospital Zurich, Schmelzbergstr. 12, 8091 Zurich, Switzerland.
authors.forename: Philipp S
authors.initials: PS
authors.lastname: Lienemann
authors.affiliation: Laboratory for Cell and Tissue Engineering, Department of Obstetrics, University Hospital Zurich, Schmelzbergstr. 12, 8091 Zurich, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Metzger
authors.affiliation: Laboratory for Cell and Tissue Engineering, Department of Obstetrics, University Hospital Zurich, Schmelzbergstr. 12, 8091 Zurich, Switzerland.
authors.forename: Anna-Sofia
authors.initials: AS
authors.lastname: Kiveliö
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, OIPA/103, 5232 Villigen, Switzerland.
authors.forename: Alain
authors.initials: A
authors.lastname: Blanc
authors.affiliation: Laboratory for Cell and Tissue Engineering, Department of Obstetrics, University Hospital Zurich, Schmelzbergstr. 12, 8091 Zurich, Switzerland.
authors.forename: Panagiota
authors.initials: P
authors.lastname: Papageorgiou
authors.affiliation: Swiss Light Source, Paul Scherrer Institute, 5232 Villigen, Switzerland.
authors.forename: Alberto
authors.initials: A
authors.lastname: Astolfo
authors.affiliation: Swiss Light Source, Paul Scherrer Institute, 5232 Villigen, Switzerland.
authors.forename: Bernd R
authors.initials: BR
authors.lastname: Pinzer
authors.affiliation: Division of Trauma Surgery, Center for Clinical Research, University Hospital Zurich, Sternwartstrasse 14, 8091 Zurich, Switzerland.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cinelli
authors.affiliation: Department of Cranio-Maxillofacial Surgery, Oral Biotechnology and Bioengineering, University Hospital Zurich, Frauenklinikstrasse 24, 8091 Zurich, Switzerland.
authors.forename: Franz E
authors.initials: FE
authors.lastname: Weber
authors.affiliation: 1] Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, OIPA/103, 5232 Villigen, Switzerland [2] Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, OIPA/103, 5232 Villigen, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Béhé
authors.affiliation: Laboratory for Cell and Tissue Engineering, Department of Obstetrics, University Hospital Zurich, Schmelzbergstr. 12, 8091 Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Ehrbar
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000627:therapeutic use*; D001861:Bone Regeneration / Q000502:physiology*; D001842:Bone and Bones / Q000002:abnormalities / Q000000981:diagnostic imaging* / Q000601:surgery; D004337:Drug Carriers / Q000627:therapeutic use; D005260:Female; D020100:Hydrogels / Q000737:chemistry / Q000627:therapeutic use; D006882:Hydroxyapatites / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011092:Polyethylene Glycols / Q000737:chemistry / Q000627:therapeutic use; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D055114:X-Ray Microtomography / Q000379:methods*
chemical_list: D019485:Bone Morphogenetic Proteins; D004337:Drug Carriers; D020100:Hydrogels; D006882:Hydroxyapatites; D011092:Polyethylene Glycols