Local administration of autologous synovium-derived cells improve the structural properties of anterior cruciate ligament autograft reconstruction in sheep

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Background : It is well known that the structural properties of a tendon autograft deteriorate during the remodeling phase after anterior cruciate ligament (ACL) reconstruction.Hypothesis : A local application of autologous synovium-derived cells cultured in TGF-betal-supplemented medium may inhibit the deterioration of structural properties of the tendon graft after ACL reconstruction.Study Design : Controlled laboratory studyMethods : Fifty-two mature sheep were used in this study. In each animal, the right knee underwent ACL reconstruction using the semitendinosus tendon autograft. Then, the animals were divided into 5 groups of 10 sheep each. No additional treatments were applied in Group 1, while fibrin sealant was applied around the graft in Group 2. In Group 3, autologous synovium-derived cells cultured in standard medium were applied around the graft with fibrin sealant, while autologous synovium-derived cells cultured in TGF-betal-supplemented medium were applied with fibrin s … More ealant in Group 4. In Group 5, fibrin sealant containing 20-ng TGF-betal was applied around the graft. Each animal was sacrificed at 12 weeks after the surgery. In each group, 7 and 3 sheep were used for biomechanical and histological evaluations, respectively. The remaining two sheep were used to confirm whether the applied cells infiltrated into the graft at 1 week after surgery.Results : Confocal microscope observations showed that the applied cells that were labeled before implantation infiltrated into the superficial portion of the graft at 1 week. Biomechanically, the maximum load and the stiffness of Groups 4 and 5 were significantly greater than those of Groups 1, 2, and 3. Histologically, necrotic lesions were observed in the core portion of the midsubstance in Groups 1 and 2. In Groups 3, 4, and 5, we could not find any necrotic lesions in the midsubstance. Conclusions : A local application of autologous synovium-derived cells cultured in TGF-beta1-supplemented medium, or fibrin sealant containing TGF-betal, significantly inhibit the natural deterioration of the structural properties of the tendon graft after ACL reconstruction. Less