Effects of separate application of three growth factors (TGF-beta1, EGF, and PDGF-BB) on mechanical properties of the in situ frozen-thawed anterior cruciate ligament.
OBJECTIVE
To clarify effects of a separate application of TGF-beta1, EGF, and PDGF-BB on the material properties of the in situ frozen-thawed anterior cruciate ligament.


METHODS
Twenty-eight rabbits were divided into four groups after undergoing the in situ freeze-thaw treatment in the right anterior cruciate ligament. In 3 of the 4 groups, 4 ng TGF-beta1, 20 ng EGF, and 4 microg PDGF-BB was applied to the frozen anterior cruciate ligament, respectively. In the remaining sham treatment group, only fibrin sealant as a vehicle was applied. Each animal was sacrificed at 12 weeks after surgery.


BACKGROUND
If the role of growth factors in ligament healing and remodeling is understood, better therapies can be designed for ligament trauma.


METHODS
The freeze-thaw treatment was performed three times using the originally developed cryo-probe. The cross-sectional area of the anterior cruciate ligament was measured by the optical non-contact method. After preconditioning, each specimen was stretched to failure. The ligament strain was determined with a video dimension analyzer.


RESULTS
The tensile strength and the tangent modulus of the anterior cruciate ligament in the TGF-beta1 group was significantly higher than in the sham group, but significantly lower than in the normal control group. There were no significant differences in the strength and the modulus between the EGF group, the PDGF-BB group, and the sham group.


CONCLUSIONS
In this model, an application of 4 ng TGF-beta1 significantly inhibited some of the material deterioration that occurs in the in situ frozen-thawed anterior cruciate ligament, while an application of 20 ng EGF or 4 microg PDGF-BB did not significantly affect the deterioration.


CONCLUSIONS
This information will be useful in the future to develop a new biological therapy for ligament reconstruction to prevent the graft deterioration after transplantation.
Nagumo
Akira
A
Department of Sports Medicine and Joint Reconstruction Surgery, Hokkaido University School of Medicine, Kita-ku, Sapporo 060-8638, Japan.
Yasuda
Kazunori
K
Numazaki
Hironori
H
Azuma
Hirotaka
H
Tanabe
Yoshie
Y
Kikuchi
Shin-ichi
S
Harata
Seikou
S
Tohyama
Harukazu
H
D000818:Animals; D016118:Anterior Cruciate Ligament / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology*; D000077214:Becaplermin; D001696:Biomechanical Phenomena / Q000379:methods; D015925:Cryopreservation / Q000379:methods*; D004548:Elasticity / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D011817:Rabbits; D013718:Tensile Strength / Q000187:drug effects / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000077214:Becaplermin; D004815:Epidermal Growth Factor