Effects of osteoinduction on bone regeneration in distraction: Results of a pilot study

Kroczek, A.; Park, J.; Birkholz, T.; Neukam, F.W.; Wiltfang, J.; Kessler, P.

doi:10.1016/j.jcms.2009.10.010

« Previous Next »Journal of Cranio-Maxillo-Facial Surgery
Volume 38, Issue 5 , Pages 334-344, July 2010

Effects of osteoinduction on bone regeneration in distraction: Results of a pilot study☆

A. Kroczek, DDS
- Department of Oral and Maxillofacial Surgery, University Hospitals Erlangen, Glueckstrasse 11, D-91054 Erlangen, Germany
J. Park, DDS
- Nikolaus Fiebiger Centre of Molecular Medicine, Department of Experimental Medicine I, University of Erlangen-Nuremberg, Glueckstrasse 6, D-91054 Erlangen, Germany
T. Birkholz, MD
- Department of Anaesthesiology, University Hospitals Erlangen, Krankenhausstrasse 12, D-91054 Erlangen, Germany
F.W. Neukam, MD, DDS (Professor, Director)
- Department of Oral and Maxillofacial Surgery, University Hospitals Erlangen, Glueckstrasse 11, D-91054 Erlangen, Germany
J. Wiltfang, MD, DDS (Professor, Director)
- Department of Oral and Maxillofacial Surgery, University Hospital Kiel, Arnold-Heller-Strasse 16, D-24105 Kiel, Germany
P. Kessler, MD, DDS (Professor, Director)
- Department of Cranio-Maxillofacial Surgery, Maastricht Universitair Medisch Centrum, P. Debyelaan 24, Postbus 5800, NL-6200 Maastricht, The Netherlands
- Prof. P. KESSLER, MD, DDS, Department of Cranio-Maxillofacial Surgery, MUMC Maastricht Universitair Medisch Centrum, Postbus 5800, NL-6200 AZ Maastricht, The Netherlands. Tel.: +31 43 3872010; Fax: +31 43 3871734.

Received 4 January 2009; accepted 6 October 2009. published online 12 November 2009.

Summary

Rate and frequency of distraction as well as stimulatory effects transmitted by growth factors and local gene therapy have a decisive influence on bone regeneration.

In a pilot study we tested the effect of four different morphogenetic and mitotic proteins and a genetically transferred vector system on bone healing in continuous osteodistraction in a large animal experiment on 24 Goettingen mini-pigs. For this purpose bone morphogenetic protein (BMP-2), BMP-7, TGF-β, IGF-1 and a liposome vector were instilled into the distraction gap. The animals were killed after 1–4 weeks of consolidation.

Histological and radiological evaluations showed maximum bone formation after the application of BMP-2/7, whereas the application of TGF-β, IGF-1 and the liposomal vector had only a limited effect on bone regeneration. The quantitative analysis demonstrated an average amount of bone in the distraction gap of 50% and 61% after instillation of BMP-2 and 7, respectively. The BMP-2 expression, however, was maximal after induction with the non-viral vector. Only after BMP-2/7 application could physical, radiographic and histological evidence of bone union be detected.

In bone distraction with a short observation period the application of morphogenetic proteins seems to enhance bone regeneration significantly. Before application in humans further studies are necessary to measure the dose-effect relationship, the mode of application and the efficacy of different inductive proteins. The combination of osteodistraction with osteoinduction, however, could shorten treatment times dramatically.

Keywords: distraction, osteoinduction, gene therapy, bone regeneration