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Effects of Local Administration of Vascular Endothelial Growth Factor on Properties of the in Situ Frozen-Thawed Anterior Cruciate Ligament in Rabbits

Young-Jin Ju, MD^*,, Harukazu Tohyama, MD, PhD^*,, Eiji Kondo, MD, PhD^*, Toshikazu Yoshikawa, MD, PhD^*, Takeshi Muneta, MD, PhD, Kenichi Shinomiya, MD, PhD and Kazunori Yasuda, MD, PhD^*

From the ^* Department of Sports Medicine and Joint Reconstruction Surgery, Hokkaido University School of Medicine, Sapporo, Japan, the Section of Orthopedic Surgery, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan, and the Department of Orthopaedic Surgery, Tokyo Medical and Dental University School of Medicine, Tokyo, Japan

Address correspondence to Harukazu Tohyama, MD, PhD, Department of Sports Medicine and Joint Reconstruction Surgery, Hokkaido University School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan (e-mail: tohyama{at}med.hokudai.ac.jp).

Background: In the autogenous tendon for anterior cruciate ligament reconstruction, intrinsic fibroblasts are necrotized immediately after surgery, and repopulation and revascularization occur. Vascular endothelial growth factor is considered to be a potent mediator of angiogenesis.

Hypothesis: An application of vascular endothelial growth factor significantly enhances angiogenesis in the in situ frozen anterior cruciate ligament, and the application significantly affects mechanical properties of the in situ frozen anterior cruciate ligament.

Study Design: Controlled laboratory study.

Methods: Right anterior cruciate ligaments from 66 rabbits underwent the freeze-thaw treatment, and animals were then divided into 3 groups. Group I served as a freeze-thaw but otherwise untreated control. In group II, 0.2 mL phosphate-buffered saline alone was applied. In group III, 30 µg vascular endothelial growth factor was applied. The groups were compared on the basis of histologic revascularization examinations using the Chalkley score, an indicator of the microvessel density, and mechanical evaluations, which included the anterior-posterior translation of the tibia relative to the femur during ± 10 N of anterior-posterior load and the mechanical properties of the anteromedial bundle of the anterior cruciate ligament.

Results: Group III’s Chalkley score was significantly greater than that of groups I and II. The tensile strength and the tangent modulus of anterior cruciate ligaments in groups I, II, and III were significantly lower than those of a normal anterior cruciate ligament, although there were no significant differences among groups I, II, and III.

Conclusion: Vascular endothelial growth factor, as administered in this study, significantly promoted angiogenesis in the devitalized anterior cruciate ligament with in situ freeze-thaw treatment, but it did not affect the mechanical properties of the in situ frozen-thawed anterior cruciate ligament in the rabbit model.

Clinical Relevance: An application of the recombinant anterior cruciate ligament is a potential future strategy to enhance revascularization of the autograft in anterior cruciate ligament reconstruction.

Key Words: angiogenesis • anterior cruciate ligament reconstruction • biomechanical properties • vascular endothelial growth factor (VEGF)

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