Complexation and sequestration of BMP-2 from an ECM mimetic hyaluronan gel for improved bone formation.
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Kisiel M, Klar AS, Ventura M, Buijs J, Mafina MK, Cool SM, Hilborn J
PLoS ONE 8 (10) e78551 [2013-10-22; online 2013-10-22]
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.
PubMed 24167632
DOI 10.1371/journal.pone.0078551
Crossref 10.1371/journal.pone.0078551
pii: PONE-D-13-23835
pmc: PMC3805527