Details

Autor(en) / Beteiligte

• van de Watering, F.C.J.
• van den Beucken, J.J.J.P.
• van der Woning, S.P.
• Briest, A.
• Eek, A.
• Qureshi, H.
• Winnubst, L.
• Boerman, O.C.
• Jansen, J.A.

Titel

Non-glycosylated BMP-2 can induce ectopic bone formation at lower concentrations compared to glycosylated BMP-2

Ist Teil von

• Journal of controlled release, 2012-04, Vol.159 (1), p.69-77

Ort / Verlag

Kidlington: Elsevier B.V

Erscheinungsjahr

2012

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Bone morphogenic protein-2 (BMP-2) is a well-known growth factor that can improve the biological performance of bone substitute materials. BMP-2 produced via bacterial expression systems are non-glycosylated (ng) whereas native and recombinant equivalents produced in mammalian cell expression systems are glycosylated (g) proteins. ngBMP-2 is less soluble, resulting in lower BMP-2 release from carriers as used as bone substitute materials. This seems promising for reducing the amount of included growth factor in bone substitute materials. Hence, it was hypothesized that ngBMP-2 would induce formation of the same amount of bone at an ectopic site at lower dosage as gBMP-2. To that end, gBMP-2 and ngBMP-2 were firstly in vitro comparatively evaluated for biological activity and release from a calcium phosphate (CaP) based bone substitute material. Thereafter, an ectopic implantation model in rats was used, in which gBMP-2 and ngBMP2 were loaded in various dosages (2–20μg/implant) on the CaP-based bone substitute material and implanted for 4 and 12weeks. The results revealed that both the in vitro biological activity of and the in vitro release of ngBMP-2 are lower compared to gBMP2. Upon ectopic implantation, however, ngBMP-2 loaded implants induced more bone formation at lower concentrations from 4-weeks onward compared to gBMP-2 equivalents, indicating the value of ngBMP-2 as a potential alternative for mammalian produced recombinant BMP-2 for bone regenerative therapies. Calcium phosphate based bone substitute material was loaded with non-glycosylated or glycosylated BMP-2. Despite lower release in vitro, ngBMP-2 significantly increased ectopic bone formation compared to gBMP-2. [Display omitted]