Abstract
The present study was conducted to test a hypothesis that the ex vivo supplementation of TGF-beta1 into medium will significantly improve the mechanical properties of the fibrous tissue regenerated in the patellar tendon defect after transplantation of cultured autologous synovium-derived fibroblasts. Thirty rabbits were divided into the following three groups. In Group A, we applied phosphate buffered saline of 0.1 ml to the defect created in the patellar tendon. In Group B, we transplanted autologous fibroblasts, which had been cultured into the tendon defect. In Group C, we transplanted autologous fibroblasts, which had been cultured with supplementation of TGF-beta1, into the tendon defect. Animals were killed at 6 weeks, and the regenerated tissue was examined for biomechanics and histology. The tangent modulus and the tensile strength of Group C were significantly higher than that of Group B, while the tensile strength of Group C was significantly lower than that of Group A. Histologically, vascular formation was abundantly found in the regenerated tissue of Groups B and C as compared to the regenerated tissues in Group A. The present study showed that transplantation of cultured autologous synovium-derived fibroblasts enhanced vascular formation in the fibrous tissue regenerated in the patellar tendon defect, while cell transplantation deteriorated the mechanical properties of the regenerated fibrous tissue. However, the ex vivo supplementation of TGF-beta1 into the medium significantly decreased mechanical deterioration of the fibrous tissue regenerated in the tendon defect after transplantation of cultured autologous synovium-derived fibroblasts.
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Alvares O, Klebe R, Grant G, Cochran DL (1995) Growth factor effects on the expression of collagenase and TIMP-1 in periodontal ligament cells. J Periodontol 66:552–558
Anaguchi Y, Yasuda K, Majima T, Tohyama H, Minami A, Hayashi K (2005) The effect of transforming growth factor-beta on mechanical properties of the fibrous tissue regenerated in the patellar tendon after resecting the central portion. Clin Biomech (Bristol, Avon) 20:959–965
Azuma H, Yasuda K, Tohyama H, Sakai T, Majima T, Aoki Y, Minami A (2003) Timing of administration of transforming growth factor-beta and epidermal growth factor influences the effect on material properties of the in situ frozen-thawed anterior cruciate ligament. J Biomech 36(3):373–381
Awad HA, Butler DL, Boivin GP, Smith FN, Malaviya P, Huibregtse B, Caplan AI (1999) Autologous mesenchymal stem cell-mediated repair of tendon. Tissue Eng 5:267–277
Awad HA, Boivin GP, Dressler MR, Smith FN, Young RG, Butler DL (2003) Repair of patellar tendon injuries using a cell-collagen composite. J Orthop Res 21:420–431
Beck LS, DeGuzman L, Lee WP, Xu Y, Siegel MW, Amento EP (1993) One systemic administration of transforming growth factor-beta 1 reverses age- or glucocorticoid-impaired wound healing. J Clin Invest 92:2841–2849
Beynnon BD, Proffer D, Drez DJ Jr, Stankewich CJ, Johnson RJ (1995) Biomechanical assessment of the healing response of the rabbit patellar tendon after removal of its central third. Am J Sports Med 23:452–457
Burks RT, Haut RC, Lancaster RL (1990) Biomechanical and histological observations of the dog patellar tendon after removal of its central one-third. Am J Sports Med 18:146–153
DesRosiers EA, Yahia L, Rivard CH (1996) Proliferative and matrix synthesis response of canine anterior cruciate ligament fibroblasts submitted to combined growth factors. J Orthop Res 14:200–208
Dunn MG, Liesch JB, Tiku ML, Zawadsky JP (1995) Development of fibroblast-seeded ligament analogs for ACL reconstruction. J Biomed Mater Res 29:1363–1371
Halliday DA, Clemente G, Rathjen DA, Ferrante A (2000) Rapid degradation of articular cartilage proteoglycan by neutrophils: comparison with macrophages and synovial fibroblasts. Inflamm Res 49:441–444
Kondo E, Katsura T, Azuma C, Taniguro Y, Hayashi R, Tohyama H, Yasuda K (2007) Local administration of synovium-derived fibroblasts cultured in TGF-beta1 supplemented medium inhibits reduction of structural properties of the tendon autograft after anterior cruciate ligament reconstruction: a sheep model study. In: Transaction of the 53rd annual meeting of the orthopaedic research society, San Diego, California, p 808
Lee TQ, Woo SL-Y (1988) A new method for determining cross-sectional shape and area of soft tissues. J Biomech Eng 110:110–114
Marui T, Niyibizi C, Georgescu HI, Cao M, Kavalkovich KW, Levine RE, Woo SLV (1997) Effect of growth factors on matrix synthesis by ligament fibroblasts. J Orthop Res 15:18–23
Mauviel A (1993) Cytokine regulation of metalloproteinase gene expression. J Cell Biochem 53:288–295
Miyashita H, Ochi M, Ikuta Y (1997) Histological and biomechanical observations of the rabbit patellar tendon after removal of its central one-third. Arch Orthop Trauma Surg 116:454–462
Nagumo A, Yasuda K, Numazaki H, Azuma H, Tanabe Y, Kikuchi S, Harata S, Tohyama H (2005) 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. Clin Biomech (Bristol, Avon) 20(3):283–290
O’Kane S, Ferguson MW (1997) Transforming growth factor beta s and wound healing. Int J Biochem Cell Biol 29:63–78
Okuizumi T, Tohyama H, Kondo E, Yasuda K (2004) The effect of cell-based therapy with autologous synovial fibroblasts activated by exogenous TGF-beta1 on the in situ frozen-thawed anterior cruciate ligament. J Orthop Sci 9:488–494
Sakai T, Yasuda K, Tohyama H, Azuma H, Nagumo A, Majima T, Frank CB (2002) Effects of combined administration of transforming growth factor-beta1 and epidermal growth factor on properties of the in situ frozen anterior cruciate ligament in rabbits. J Orthop Res 20(6):1345–1351
Tohyama H, Yasuda K, Kitamura Y, Yamamoto E, Hayashi K (2003) The changes in mechanical properties of regenerated and residual tissues in the patellar tendon after removal of its central portion. Clin Biomech 18:765–772
Uria JA, Jimenez MG, Balbin M, Freije JM, Lopez-Otin C (1998) Differential effects of transforming growth factor-beta on the expression of collagenase-1 and collagenase-3 in human fibroblasts. J Biol Chem 273:9769–9777
Woo SL, Hildebrand K, Watanabe N, Fenwick JA, Papageorgiou CD, Wang JH (1999) Tissue engineering of ligament and tendon healing. Clin Orthop Relat Res 367:S312–S323
Yamamoto N, Hayashi K, Kuriyama H, Ohno K, Yasuda K, Kaneda K (1992) Mechanical properties of the rabbit patellar tendon. J Biomech Eng 114:332–337
Yamamoto E, Hayashi K, Yamamoto N (1999) Mechanical properties of collagen fascicles from the rabbit patellar tendon. J Biomech Eng 121:124–131
Yasuda K, Tomita F, Yamazaki S, Minami A, Tohyama H (2004) The effect of growth factors on biomechanical properties of the bone-patellar tendon-bone graft after anterior cruciate ligament reconstruction: a canine model study. Am J Sports Med 32(4):870–880
Young RG, Butler DL, Weber W, Caplan AI, Gorden SL, Fink DJ (1998) Use of mesenchymal stem cells in a collagen matrix for Achilles tendon repair. J Orthop Res 16:406–413
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Okamoto, S., Tohyama, H., Kondo, E. et al. Ex vivo supplementation of TGF-beta1 enhances the fibrous tissue regeneration effect of synovium-derived fibroblast transplantation in a tendon defect: a biomechanical study. Knee Surg Sports Traumatol Arthr 16, 333–339 (2008). https://doi.org/10.1007/s00167-007-0400-2
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DOI: https://doi.org/10.1007/s00167-007-0400-2