Reverse Dynamization: Influence of Fixator Stiffness on the Mode and Efficiency of Large-Bone-Defect Healing at Different Doses of rhBMP-2.
BACKGROUND
Reverse dynamization is a technology for enhancing the healing of osseous defects. With use of an external fixator, the axial stiffness across the defect is initially set low and subsequently increased. The purpose of the study described in this paper was to explore the efficacy of reverse dynamization under different conditions.


METHODS
Rat femoral defects were stabilized with external fixators that allowed the stiffness to be modulated on living animals. Recombinant human bone morphogenetic protein-2 (rhBMP-2) was implanted into the defects on a collagen sponge. Following a dose-response experiment, 5.5 μg of rhBMP-2 was placed into the defect under conditions of very low (25.4-N/mm), low (114-N/mm), medium (185-N/mm), or high (254-N/mm) stiffness. Reverse dynamization was evaluated with 2 different starting stiffnesses: low (114 N/mm) and very low (25.4 N/mm). In both cases, high stiffness (254 N/mm) was imposed after 2 weeks. Healing was assessed with radiographs, micro-computed tomography (μCT), histological analysis, and mechanical testing.


RESULTS
In the absence of dynamization, the medium-stiffness fixators provided the best healing. Reverse dynamization starting with very low stiffness was detrimental to healing. However, with low initial stiffness, reverse dynamization considerably improved healing with minimal residual cartilage, enhanced cortication, increased mechanical strength, and smaller callus. Histological analysis suggested that, in all cases, healing provoked by rhBMP-2 occurred by endochondral ossification.


CONCLUSIONS
These data confirm the potential utility of reverse dynamization as a way of improving bone healing but indicate that the stiffness parameters need to be selected carefully.


CONCLUSIONS
Reverse dynamization may reduce the amount of rhBMP-2 needed to induce healing of recalcitrant osseous lesions, reduce the time to union, and decrease the need for prolonged external fixation.
Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, Queensland, Australia vaida.glatt@qut.edu.au.
Vaida
V
Glatt
Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, Queensland, Australia.
Nicole
N
Bartnikowski
Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, Queensland, Australia Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, Minnesota.
Nicholas
N
Quirk
Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, Queensland, Australia Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Michael
M
Schuetz
Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, Minnesota.
Christopher
C
Evans
D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D005592:Fracture Fixation / Q000379:methods*; D017102:Fracture Healing / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D016212:Transforming Growth Factor beta / Q000008:administration & dosage*; D016896:Treatment Outcome
D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2