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. Raina, D. B., Larsson, D., Mrkonjic, F., Isaksson, H., Kumar, A., Lidgren, L., & Tägil, M. Journal of Controlled Release: Official Journal of the Controlled Release Society, 272:83–96, 2018. doi abstract bibtex 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 4weeks. Using single photon emission computed tomography (SPECT), the release kinetics of 125I-rhBMP-2 in-vivo was followed for 4weeks 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 4weeks (13±0.1%). In-vivo, an initial release of 43.2±7.6% of 14C-ZA was detected after 1day, 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.
@article{raina_gelatin-_2018,
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},
volume = {272},
issn = {1873-4995},
doi = {10.1016/j.jconrel.2018.01.006},
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. 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 4weeks. Using single photon emission computed tomography (SPECT), the release kinetics of 125I-rhBMP-2 in-vivo was followed for 4weeks 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 4weeks (13±0.1\%). In-vivo, an initial release of 43.2±7.6\% of 14C-ZA was detected after 1day, 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.},
language = {eng},
journal = {Journal of Controlled Release: Official Journal of the Controlled Release Society},
author = {Raina, Deepak Bushan and Larsson, David and Mrkonjic, Filip and Isaksson, Hanna and Kumar, Ashok and Lidgren, Lars and Tägil, Magnus},
year = {2018},
pmid = {29329716},
keywords = {Animals, Biocompatible Materials, Bone Density Conservation Agents, Bone Morphogenetic Protein 2, Bone morphogenic protein (BMP), Calcium Sulfate, Cell Line, Cell Survival, Cryogels, Delayed-Action Preparations, Durapatite, Gelatin, Hydroxyapatite, In-vivo BMP release, In-vivo ZA release, Male, Mice, Osteogenesis, Rats, Sprague-Dawley, Recombinant Proteins, Transforming Growth Factor beta, Zoledronic Acid, Zoledronic acid (ZA)},
pages = {83--96},
}
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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 4weeks. Using single photon emission computed tomography (SPECT), the release kinetics of 125I-rhBMP-2 in-vivo was followed for 4weeks 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 4weeks (13±0.1%). In-vivo, an initial release of 43.2±7.6% of 14C-ZA was detected after 1day, 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.","language":"eng","journal":"Journal of Controlled Release: Official Journal of the Controlled Release Society","author":[{"propositions":[],"lastnames":["Raina"],"firstnames":["Deepak","Bushan"],"suffixes":[]},{"propositions":[],"lastnames":["Larsson"],"firstnames":["David"],"suffixes":[]},{"propositions":[],"lastnames":["Mrkonjic"],"firstnames":["Filip"],"suffixes":[]},{"propositions":[],"lastnames":["Isaksson"],"firstnames":["Hanna"],"suffixes":[]},{"propositions":[],"lastnames":["Kumar"],"firstnames":["Ashok"],"suffixes":[]},{"propositions":[],"lastnames":["Lidgren"],"firstnames":["Lars"],"suffixes":[]},{"propositions":[],"lastnames":["Tägil"],"firstnames":["Magnus"],"suffixes":[]}],"year":"2018","pmid":"29329716","keywords":"Animals, Biocompatible Materials, Bone Density Conservation Agents, Bone Morphogenetic Protein 2, Bone morphogenic protein (BMP), Calcium Sulfate, Cell Line, Cell Survival, Cryogels, Delayed-Action Preparations, Durapatite, Gelatin, Hydroxyapatite, In-vivo BMP release, In-vivo ZA release, Male, Mice, Osteogenesis, Rats, Sprague-Dawley, Recombinant Proteins, Transforming Growth Factor beta, Zoledronic Acid, Zoledronic acid (ZA)","pages":"83–96","bibtex":"@article{raina_gelatin-_2018,\n\ttitle = {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},\n\tvolume = {272},\n\tissn = {1873-4995},\n\tdoi = {10.1016/j.jconrel.2018.01.006},\n\tabstract = {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 4weeks. Using single photon emission computed tomography (SPECT), the release kinetics of 125I-rhBMP-2 in-vivo was followed for 4weeks 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 4weeks (13±0.1\\%). In-vivo, an initial release of 43.2±7.6\\% of 14C-ZA was detected after 1day, after which the scaffold retained the remaining ZA during 4-weeks. 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