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Gelatin- hydroxyapatite- calcium sulphate based biomaterial for long term sustained delivery of bone morphogenic protein-2 and zoledronic acid for increased bone formation: In-vitro and in-vivo carrier properties
Umeå University, Faculty of Medicine. Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopedics, Lund 221 85, Sweden.
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2018 (English)In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 272, p. 83-96Article in journal (Refereed) Published
Abstract [en]

In this study, a novel macroporous composite biomaterial consisting of gelatin-hydroxyapatite-calcium sulphate for delivery of bone morphogenic protein-2 (rhBMP-2) and zoledronic acid (ZA) has been developed. The biomaterial scaffold has a porous structure and functionalization of the scaffold with rhBMP-2 induces osteogenic differentiation of MC3T3-e1 cells seen by a significant increase in biochemical and genetic markers of osteoblastic differentiation. In-vivo muscle pouch experiments showed higher mineralization using scaffold + rhBMP-2 when compared to an approved absorbable collagen sponge (ACS) + rhBMP-2 as verified by micro-CT. Co-delivery of rhBMP-2 + ZA via the novel scaffold enabled a reduction in the effective rhBMP-2 doses. The presence of tartrate resistant acid phosphatase staining in the rhBMP-2 group indicates osteoclastic resorption, which could be stalled by adding ZA, which by speculation could explain the net increase in mineralization. The new scaffold allowed for slow release of rhBMP-2 in-vitro (3.3 +/- 0.1%) after 4 weeks. Using single photon emission computed tomography (SPECT), the release kinetics of I-125-rhBMP-2 in-vivo was followed for 4 weeks and a total of 65.3 +/- 15.2% I-125-rhBMP-2 was released from the scaffolds. In-vitro C-14-ZA release curve shows an initial burst release on day 1 (8.8 +/- 0.7%) followed by a slow release during the following 4 weeks (13 +/- 0.1%). In-vivo, an initial release of 43.2 +/- 7.6% of C-14-ZA was detected after 1 day, after which the scaffold retained the remaining ZA during 4-weeks. Taken together, our results show that the developed biomaterial is an efficient carrier for spatio-temporal delivery of rhBMP-2 and ZA leading to increased bone formation compared to commercially available carrier for rhBMP-2.

Place, publisher, year, edition, pages
2018. Vol. 272, p. 83-96
Keywords [en]
Cryogels, Bone morphogenic protein (BMP), Zoledronic acid (ZA), In-vivo BMP release, In-vivo ZA lease, Gelatin, Hydroxyapatite
National Category
Medical Materials
Identifiers
URN: urn:nbn:se:umu:diva-145583DOI: 10.1016/j.jconrel.2018.01.006ISI: 000425380700009PubMedID: 29329716OAI: oai:DiVA.org:umu-145583DiVA, id: diva2:1192255
Funder
Swedish Research Council, 2015-06717VINNOVA, 2017-00269Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2018-03-22Bibliographically approved

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