Ehbmp-2

Abstract

For the first time a non natural BMP-variant (EHBMP-2) with osteoinductive properties was produced by expression in E. coli through specific mutation of the amino acid sequence. The substitution of 12 N-terminal amino acids by a nonsense sequence results in a neglectible affinity of EHBMP-2 to the extracellular matrix. In vitro EHBMP-2 induces dose-dependent cartilage formation in neonatal muscle tissue. Single intramuscular implantation in mice results in the formation of an ossicle with functional active bone marrow. The size of the ossicle depends on the amount of implanted EHBMP-2 and can significantly be increased by the combination with a collagen carrier. The largest bone formation is observed after injection of EHBMP-2 containing collagen suspensions. In rats a stronger osteoinductive activity can be achieved by coupling of EHBMP-2 to collagen discs than by coupling natural BMP-2 to the same collagen carrier. Critical size defects in rats' mandibular angels can be restored by the combination of granular collagenous bone matrix (ICBM) with EHBMP-2. Further investigations have to show whether the altered pharmacokinetics of EHBMP-2 has advantages regarding its therapeutical use and tissue-engineering.

Analysis of hydrolyzable polyethylene glycol hydrogels and deproteinized bone mineral as delivery systems for glycosylated and non-glycosylated bone morphogenetic protein-2

“…Moreover, instead of the expected release after immersion of to hydroxyapatite is higher than the affinity of bovine serum albumin to hydroxyapatite [37]. The reduced activity of the supernatant, however, does not necessarily imply a reduced activity in vivo, as indicated by successful studies on the combination of DBBM and rhBMP-2 [9,32,39]. rhBMP-2 could be adsorbed to DBBM in an active or a denatured form, or it could be that it is reactivated upon release after the slow degradation of DBBM in vivo.…”