title: Protein composition alters in vivo resorption of PEG-based hydrogels as monitored by contrast-enhanced MRI.
abstract: We report on the use of magnetic resonance imaging (MRI)-based non-invasive monitoring to document the role of protein adjuvants in hydrogel implant integration in vivo. Polyethylene glycol (PEG) hydrogels were formed with different protein constituents, including albumin, fibrinogen and gelatin. The hydrogels were designed to exhibit similar material properties, including modulus, swelling and hydrolytic degradation kinetics. The in vivo resorption properties of these PEG-based hydrogels, which contained a tethered gadolinium contrast agent, were characterized by MRI and histology, and compared to their in vitro characteristics. MRI data revealed that PEG-Albumin implants remained completely intact throughout the experiments, PEG-Fibrinogen implants lost about 10% of their volume and PEG-Gelatin implants underwent prominent swelling and returned to their initial volume by day 25. Fully synthetic PEG-diacrylate (PEG-DA) control hydrogels lost about half of their volume after 25 days in vivo. Transverse MRI cross-sections of the implants revealed distinct mechanisms of the hydrogel's biodegradation: PEG-Fibrinogen and PEG-Albumin underwent surface erosion, whereas PEG-Gelatin and PEG-DA hydrogels mainly underwent bulk degradation. Histological findings substantiated the MRI data and demonstrated significant cellular response towards PEG-DA and PEG-Gelatin scaffolds with relatively low reaction towards PEG-Fibrinogen and PEG-Albumin hydrogels. These findings demonstrate that PEG-protein hydrogels can degrade via a different mechanism than PEG hydrogels, and that this difference can be linked to a reduced foreign body response.
authors.affiliation: Faculty of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Berdichevski
authors.affiliation: Regentis Biomaterials Ltd., Or Akiva 30600, Israel.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Shachaf
authors.affiliation: Regentis Biomaterials Ltd., Or Akiva 30600, Israel.
authors.forename: Roni
authors.initials: R
authors.lastname: Wechsler
authors.affiliation: Faculty of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel. Electronic address: dror@bm.technion.ac.il.
authors.forename: Dror
authors.initials: D
authors.lastname: Seliktar
mesh_terms: D000818:Animals; D002138:Calibration; D002417:Cattle; D003287:Contrast Media; D005340:Fibrinogen / Q000378:metabolism; D005682:Gadolinium / Q000737:chemistry; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D011917:Rats, Inbred Lew; D012710:Serum Albumin, Bovine / Q000378:metabolism; D040521:Subcutaneous Tissue / Q000473:pathology; D034421:Sus scrofa
chemical_list: D003287:Contrast Media; D020100:Hydrogels; D011506:Proteins; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D005780:Gelatin; D005340:Fibrinogen; D005682:Gadolinium
keywords: Biodegradation; Biomaterial scaffold; Contrast agents; Implant biocompatibility; MRI; PEG hydrogel