TY - JOUR

T1 - The effect of an rhBMP-2 absorbable collagen sponge-targeted system on bone formation in vivo

AU - Visser, Rick

AU - Arrabal, Pilar M.

AU - Becerra, Jose

AU - Rinas, Ursula

AU - Cifuentes, Manuel

N1 - Funding Information: The authors would like to thank Ms. Silvia Hernández and Ms. Eva Jiménez for technical support. Thanks also to Dr. Luis Felipe Vallejo for his valuable help in protein production and refolding. This work was partially supported by Red TerCel RD06/0010/0014 (Ministerio de Sanidad y Consumo), BIO2006-03599 (Ministerio de Educación y Ciencia), TCRM 0012/2006 (Consejería de Salud, Junta de Andalucía) and P07-CVI-02781 (Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía).

PY - 2009/4

Y1 - 2009/4

N2 - Reparation of bone defects remains a major clinical and economic concern, with more than 3 million bone grafts performed annually only in the United States and the EU. The search for alternatives to autologous bone grafting led to the approval by the FDA of an absorbable collagen carrier combined with rhBMP-2 for the treatment of certain bone diseases and fractures. The present work is focused on the production of a collagen-targeted rhBMP-2 based system to improve bone formation. We produced a modified rhBMP-2 with only an additional collagen-binding decapeptide derived from the von Willebrand factor and tested its affinity to collagen and its ability to induce ectopic bone formation in vivo when implanted in combination with absorbable collagen sponges or hydroxyapatite. The results showed not only that the rhBMP2-CBD had an increased affinity to collagen, but also that this binding was very stable during a prolonged period of time. In vivo experiments demonstrated that this rhBMP2-CBD maintained its osteoinductive activity, being capable of inducing new bone formation even at lower concentrations than native rhBMP-2. These results indicate that the combination of the fusion protein with absorbable collagen may be a suitable and safer alternative to rhBMP-2 for bone repair purposes.

AB - Reparation of bone defects remains a major clinical and economic concern, with more than 3 million bone grafts performed annually only in the United States and the EU. The search for alternatives to autologous bone grafting led to the approval by the FDA of an absorbable collagen carrier combined with rhBMP-2 for the treatment of certain bone diseases and fractures. The present work is focused on the production of a collagen-targeted rhBMP-2 based system to improve bone formation. We produced a modified rhBMP-2 with only an additional collagen-binding decapeptide derived from the von Willebrand factor and tested its affinity to collagen and its ability to induce ectopic bone formation in vivo when implanted in combination with absorbable collagen sponges or hydroxyapatite. The results showed not only that the rhBMP2-CBD had an increased affinity to collagen, but also that this binding was very stable during a prolonged period of time. In vivo experiments demonstrated that this rhBMP2-CBD maintained its osteoinductive activity, being capable of inducing new bone formation even at lower concentrations than native rhBMP-2. These results indicate that the combination of the fusion protein with absorbable collagen may be a suitable and safer alternative to rhBMP-2 for bone repair purposes.

KW - BMP (bone morphogenetic protein)

KW - Bone tissue engineering

KW - Collagen

KW - Osteogenesis

KW - Recombinant protein

UR - http://www.scopus.com/inward/record.url?scp=59849120814&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2008.12.046

DO - 10.1016/j.biomaterials.2008.12.046

M3 - Article

C2 - 19155065

AN - SCOPUS:59849120814

VL - 30

SP - 2032

EP - 2037

JO - BIOMATERIALS

JF - BIOMATERIALS

SN - 0142-9612

IS - 11

ER -