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
(2018) In Journal of Controlled Release 272. p.83-96- Abstract
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.... (More)
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 125I–rhBMP-2 in-vivo was followed for 4 weeks and a total of 65.3 ± 15.2% 125I–rhBMP-2 was released from the scaffolds. In-vitro 14C–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 14C–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.
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- author
- Raina, Deepak Bushan LU ; Larsson, David LU ; Mrkonjic, Filip ; Isaksson, Hanna LU ; Kumar, Ashok LU ; Lidgren, Lars LU and Tägil, Magnus LU
- organization
- publishing date
- 2018-02-28
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Bone morphogenic protein (BMP), Cryogels, Gelatin, Hydroxyapatite, In-vivo BMP release, In-vivo ZA release, Zoledronic acid (ZA)
- in
- Journal of Controlled Release
- volume
- 272
- pages
- 14 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:29329716
- scopus:85040315693
- ISSN
- 0168-3659
- DOI
- 10.1016/j.jconrel.2018.01.006
- language
- English
- LU publication?
- yes
- id
- be1306b9-dc13-4ed6-a7ab-e01a4adac0e2
- date added to LUP
- 2018-01-22 09:12:42
- date last changed
- 2024-09-16 15:31:38
@article{be1306b9-dc13-4ed6-a7ab-e01a4adac0e2, abstract = {{<p>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 <sup>125</sup>I–rhBMP-2 in-vivo was followed for 4 weeks and a total of 65.3 ± 15.2% <sup>125</sup>I–rhBMP-2 was released from the scaffolds. In-vitro <sup>14</sup>C–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 <sup>14</sup>C–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.</p>}}, author = {{Raina, Deepak Bushan and Larsson, David and Mrkonjic, Filip and Isaksson, Hanna and Kumar, Ashok and Lidgren, Lars and Tägil, Magnus}}, issn = {{0168-3659}}, keywords = {{Bone morphogenic protein (BMP); Cryogels; Gelatin; Hydroxyapatite; In-vivo BMP release; In-vivo ZA release; Zoledronic acid (ZA)}}, language = {{eng}}, month = {{02}}, pages = {{83--96}}, publisher = {{Elsevier}}, series = {{Journal of Controlled Release}}, title = {{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}}, url = {{http://dx.doi.org/10.1016/j.jconrel.2018.01.006}}, doi = {{10.1016/j.jconrel.2018.01.006}}, volume = {{272}}, year = {{2018}}, }