title: Using bimodal MRI/fluorescence imaging to identify host angiogenic response to implants.
abstract: Therapies that promote angiogenesis have been successfully applied using various combinations of proangiogenic factors together with a biodegradable delivery vehicle. In this study we used bimodal noninvasive monitoring to show that the host response to a proangiogenic biomaterial can be drastically affected by the mode of implantation and the surface area-to-volume ratio of the implant material. Fluorescence/MRI probes were covalently conjugated to VEGF-bearing biodegradable PEG-fibrinogen hydrogel implants and used to document the in vivo degradation and liberation of bioactive constituents in an s.c. rat implantation model. The hydrogel biodegradation and angiogenic host response with three types of VEGF-bearing implant configurations were compared: preformed cylindrical plugs, preformed injectable microbeads, and hydrogel precursor, injected and polymerized in situ. Although all three were made with identical amounts of precursor constituents, the MRI data revealed that in situ polymerized hydrogels were fully degraded within 2 wk; microbead degradation was more moderate, and plugs degraded significantly more slowly than the other configurations. The presence of hydrogel degradation products containing the fluorescent label in the surrounding tissues revealed a distinct biphasic release profile for each type of implant configuration. The purported in vivo VEGF release profile from the microbeads resulted in highly vascularized s.c. tissue containing up to 16-fold more capillaries in comparison with controls. These findings demonstrate that the configuration of an implant can play an important role not only in the degradation and resorption properties of the materials, but also in consequent host angiogenic response.
authors.affiliation: Faculty of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel; and.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Berdichevski
authors.affiliation: Faculty of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel; and.
authors.forename: Haneen
authors.initials: H
authors.lastname: Simaan Yameen
authors.affiliation: Departments of Veterinary Resources and.
authors.forename: Hagit
authors.initials: H
authors.lastname: Dafni
authors.affiliation: Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Neeman
authors.affiliation: Faculty of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel; and dror@bm.technion.ac.il.
authors.forename: Dror
authors.initials: D
authors.lastname: Seliktar
mesh_terms: D000818:Animals; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005453:Fluorescence; D020100:Hydrogels / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019736:Prostheses and Implants; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D003432:Cross-Linking Reagents; D020100:Hydrogels; D042461:Vascular Endothelial Growth Factor A
keywords: angiogenesis; biomaterial scaffold; contrast agents; hydrogel; tissue regeneration
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