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Non-invasive tri-modal visualisation via PET/SPECT/μCT of recombinant human bone morphogenetic protein-2 retention and associated bone regeneration: A proof of concept
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET-MRI Platform.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
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2018 (English)In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 285, p. 178-186Article in journal (Refereed) Published
Abstract [en]

Bone morphogenetic proteins (BMP's) are vital for bone and cartilage formation, where bone morphogenetic protein-2 (BMP-2) is acknowledged as a growth factor in osteoblast differentiation. However, uncontrolled delivery may result in adverse clinical effects. In this study we investigated the possibility for longitudinal and non-invasive monitoring of implanted [125I]BMP-2 retention and its relation to ossification at the site of implantation. A unilateral critically sized femoral defect was produced in the left limb of rats while the right femur was retained intact as a paired reference control. The defect was filled with a hyaluronan hydrogel with 25% hydroxyapatite alone (carrier control; n = 2) or combined with a mixture of [125I]BMP-2 (150 μg/ml; n = 4). Bone formation was monitored using micro computed tomography (μCT) scans at 1, 3, 5, 7, 9 and 12 weeks. The retention of [125I]BMP-2 was assessed with single photon emission computed tomography (SPECT), and the bone healing process was followed with sodium fluoride (Na18F) using positron emission tomography (PET) at day 3 and at week 2, 4, and 6. A rapid burst release of [125I]BMP-2 was detected via SPECT. This was followed by a progressive increase in uptake levels of [18F]fluoride depicted by PET imaging that was confirmed as bone formation via μCT. We propose that this functional, non-invasive imaging method allows tri-modal visualisation of the release of BMP-2 and the following in vivo response. We suggest that the potential of this novel technique could be considered for preclinical evaluation of novel smart materials on bone regeneration.

Place, publisher, year, edition, pages
2018. Vol. 285, p. 178-186
Keywords [en]
Bone morphogenetic protein 2, Bone tissue engineering, Hydrogel, Micro computed tomography, Positron emission tomography, Single-photon emission computed tomography
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-356465DOI: 10.1016/j.jconrel.2018.07.012ISI: 000441737400015PubMedID: 30005906OAI: oai:DiVA.org:uu-356465DiVA, id: diva2:1235860
Funder
EU, FP7, Seventh Framework Programme, 262948
Note

G. Hulsart-Billström and R. K. Selvaraju contributed equally to this work and should be regarded as joint first authors.

Available from: 2018-07-28 Created: 2018-07-28 Last updated: 2018-10-10Bibliographically approved

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Hulsart Billström, GrySelvaraju, RamkumarEstrada, SergioLubberink, MarkAsplund, VeronikaMarsell, RichardLarsson, SuneAntoni, Gunnar

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Hulsart Billström, GrySelvaraju, RamkumarEstrada, SergioLubberink, MarkAsplund, VeronikaMarsell, RichardLarsson, SuneAntoni, Gunnar
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OrthopaedicsPreclinical PET-MRI PlatformRadiologyDepartment of Medicinal ChemistryPreparative Medicinal Chemistry
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