Complexation and sequestration of BMP-2 from an ECM mimetic hyaluronan gel for improved bone formation.
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-...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3805527?pdf=render |
| _version_ | 1819100023728635904 |
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| author | Marta Kisiel Agnieszka S Klar Manuela Ventura Jos Buijs Marc-Krystelle Mafina Simon M Cool Jöns Hilborn |
| author_facet | Marta Kisiel Agnieszka S Klar Manuela Ventura Jos Buijs Marc-Krystelle Mafina Simon M Cool Jöns Hilborn |
| author_sort | Marta Kisiel |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T00:56:11Z |
| format | Article |
| id | doaj.art-38ea273698694e2f827c90c59cdefbc5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T00:56:11Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-38ea273698694e2f827c90c59cdefbc52022-12-21T18:44:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7855110.1371/journal.pone.0078551Complexation and sequestration of BMP-2 from an ECM mimetic hyaluronan gel for improved bone formation.Marta KisielAgnieszka S KlarManuela VenturaJos BuijsMarc-Krystelle MafinaSimon M CoolJöns HilbornBone 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.http://europepmc.org/articles/PMC3805527?pdf=render |
| spellingShingle | Marta Kisiel Agnieszka S Klar Manuela Ventura Jos Buijs Marc-Krystelle Mafina Simon M Cool Jöns Hilborn Complexation and sequestration of BMP-2 from an ECM mimetic hyaluronan gel for improved bone formation. PLoS ONE |
| title | Complexation and sequestration of BMP-2 from an ECM mimetic hyaluronan gel for improved bone formation. |
| title_full | Complexation and sequestration of BMP-2 from an ECM mimetic hyaluronan gel for improved bone formation. |
| title_fullStr | Complexation and sequestration of BMP-2 from an ECM mimetic hyaluronan gel for improved bone formation. |
| title_full_unstemmed | Complexation and sequestration of BMP-2 from an ECM mimetic hyaluronan gel for improved bone formation. |
| title_short | Complexation and sequestration of BMP-2 from an ECM mimetic hyaluronan gel for improved bone formation. |
| title_sort | complexation and sequestration of bmp 2 from an ecm mimetic hyaluronan gel for improved bone formation |
| url | http://europepmc.org/articles/PMC3805527?pdf=render |
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