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https://doi.org/10.1371/journal.pone.0078551
Title: | Complexation and Sequestration of BMP-2 from an ECM Mimetic Hyaluronan Gel for Improved Bone Formation | Authors: | Kisiel M. Klar A.S. Ventura M. Buijs J. Mafina M.-K. Cool S.M. Hilborn J. |
Keywords: | alkaline phosphatase bone morphogenetic protein 2 dermatan sulfate glycosaminoglycan heparin hyaluronic acid Bmp2 protein, rat bone morphogenetic protein 2 hyaluronic acid immobilized protein immunological adjuvant angiogenesis animal experiment animal model article assay binding affinity binding kinetics biological activity bone mass bone mineral bone structure complex formation controlled study covalent bond enzyme activity extracellular matrix histology immunohistochemistry in vitro study in vivo study male micro-computed tomography nonhuman ossification protein metabolism protein secretion protein stability rat scanning electron microscopy surface plasmon resonance animal bone development cell culture chemistry drug effects human Sprague Dawley rat time Adjuvants, Immunologic Animals Bone Morphogenetic Protein 2 Cells, Cultured Humans Hyaluronic Acid Immobilized Proteins Male Osteogenesis Rats Rats, Sprague-Dawley Time Factors |
Issue Date: | 2013 | Citation: | Kisiel M., Klar A.S., Ventura M., Buijs J., Mafina M.-K., Cool S.M., Hilborn J. (2013). Complexation and Sequestration of BMP-2 from an ECM Mimetic Hyaluronan Gel for Improved Bone Formation. PLoS ONE 8 (10) : e78551. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0078551 | Rights: | Attribution 4.0 International | Abstract: | Bone morphogenetic protein-2 (BMP-2) is considered a promising adjuvant for the treatment of skeletal non-union and spinal fusion. However, BMP-2 delivery in a conventional collagen scaffold necessitates a high dose to achieve an efficacious outcome. To lower its effective dose, we precomplexed BMP-2 with the glycosaminoglycans (GAGs) dermatan sulfate (DS) or heparin (HP), prior to loading it into a hyaluronic acid (HA) hydrogel. In vitro release studies showed that BMP-2 precomplexed with DS or HP had a prolonged delivery compared to without GAG. BMP-2-DS complexes achieved a slightly faster release in the first 24 h than HP; however, both delivered BMP-2 for an equal duration. Analysis of the kinetic interaction between BMP-2 and DS or HP showed that HP had approximately 10 times higher affinity for BMP-2 than DS, yet it equally stabilized the protein, as determined by alkaline phosphatase activity. Ectopic bone formation assays at subcutaneous sites in rats demonstrated that HA hydrogel-delivered BMP-2 precomplexed with GAG induced twice the volume of bone compared with BMP-2 delivered uncomplexed to GAG. © 2013 Kisiel et al. | Source Title: | PLoS ONE | URI: | https://scholarbank.nus.edu.sg/handle/10635/161459 | ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0078551 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
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