Dual non-invasive visualization of recombinant human bone morphogenetic protein-2 release and associated bone regeneration
2014 (English)Manuscript (preprint) (Other academic)
Bone morphogenetic proteins (BMP’s) are vital for bone and cartilage formation. BMP-2 is acknowledged as a key family member in osteoblast differentiation. In this study we investigated the possibility for longitudinal and non-invasive monitoring of implanted [125I]BMP-2 release and its correlation to ossification at the site of implantation. We used a unilateral rodent model with a critically sized femoral defect on the left side that was stabilized with an external fixator while the contralateral intact right femur was used as control. Male Sprague Dawley rats were randomized into two groups. The defect was filled with a hyaluronan hydrogel with 25% hydroxyapatite (n=2) alone or with the same compound combined a mixture of 30 µg of [125I]BMP-2 at a concentration of 150 µg/mL. Bone formation was followed by microCT (µCT) post surgery and thereafter at six occasions over 12 weeks. The release of [125I]BMP-2 was assessed with single photon emission computed tomography (SPECT), and the bone healing process was followed with [18F]sodium fluoride (NaF) using positron emission tomography (PET)at day 3 and at weeks 2, 4, and 6.
In the defects filled with hydrogel andBMP-2 a rapid burst release of [125I]BMP-2 was observed between day 3 and 2 weeks. A progressive increase in uptake levels of [18F]sodium fluoride followed, which reached a maximum 4 weeks post surgery. Bone formation was seen by µCT for all 12 weeks. In the hydrogel alone group, bone regeneration was observed by PET and CT at week 2 and 3 but later on no bone formation was observed in the defect. We propose that the functional, noninvasive imaging method described allow dual visualization of the release of BMP-2 and the following in vivo response, and should hereby be considered a potential novel tool for studies on bone regeneration.
Place, publisher, year, edition, pages
bone tissue engineering; hydrogel; computed tomography; positron emission tomography; single-photon emission computed tomography; bone morphogenetic protein 2
Biological Sciences Other Medical Sciences
Research subject Biology
IdentifiersURN: urn:nbn:se:uu:diva-234698OAI: oai:DiVA.org:uu-234698DiVA: diva2:758000
FunderEU, FP7, Seventh Framework Programme