Background: Ligaments and tendons do not gain mechanical properties of the native tissue after injury or grafting.
Purpose: To determine the influence of platelet-derived growth factor on tendon graft remodeling.
Study Design: Laboratory animal study.
Methods: Forty-eight sheep underwent anterior cruciate ligament reconstruction and were sacrificed after 3, 6, 12, and 24 weeks. In 6 animals at each time point, platelet-derived growth factor was locally delivered via coated sutures. After mechanical testing, tissue samples were taken for histologic, immunohistochemical, and electron microscopy evaluations.
Results: With platelet-derived growth factor treatment, cross-sectional area was significantly lower at 3 and 12 weeks. Load to failure was significantly higher at 6 weeks. Tensile stress was significantly higher at 3 and 12 weeks. Crimp length was significantly higher at 3 and 6 weeks. Vascular density was significantly higher at 6 weeks. Electron microscopy showed a significantly higher collagen fibril amount at 12 weeks. Differences in these parameters at other time points were not significant.
Conclusions: There were alterations in several but not all time points. The local application of platelet-derived growth factor alters the tissue’s mechanical properties during free tendon graft remodeling after anterior cruciate ligament reconstruction. Growth factors present a promising tool toward the complete mechanical restitution of a healing ligament substitute.
1. Allen MJ, Houlton JE, Adams SB, et al.The surgical anatomy of the stifle joint in sheep. Vet Surg. 1998;27:596-605.
2.
2. Amiel D, Kleiner JB, Akeson WH. The natural history of the anterior cruciate ligament autograft of patellar tendon origin. Am J Sports Med. 1986;14:449-462.
3.
3. Amiel D, Kleiner JB, Roux RD, et al.The phenomenon of “ligamentization”: anterior cruciate ligament reconstruction with autogenous patellar tendon. J Orthop Res. 1986;4:162-172.
4.
4. Amiel D, Nagineni CN, Choi SH, et al.Intrinsic properties of ACL and MCL cells and their responses to growth factors. Med Sci Sports Exerc. 1995;27:844-851.
5.
5. Arnoczky SP, Tarvin GB, Marshall JL. Anterior cruciate ligament replacement using patellar tendon: an evaluation of graft revascularization in the dog. J Bone Joint Surg Am. 1982;64:217-224.
6.
6. Bartold PM, Raben A.Growth factor modulation of fibroblasts in simulated wound healing. J Periodontal Res. 1996;31:205-216.
7.
7. Batten ML, Hansen JC, Dahners LE. Influence of dosage and timing of application of platelet-derived growth factor on early healing of the rat medial collateral ligament. J Orthop Res. 1996;14:736-741.
8.
8. Bennett NT, Schultz GS. Growth factors and wound healing: biochemical properties of growth factors and their receptors. Am J Surg. 1993;165:728-737.
9.
9. Bosch U, Decker B, Moller HD, et al.Collagen fibril organization in the patellar tendon autograft after posterior cruciate ligament reconstruction: a quantitative evaluation in a sheep model. Am J Sports Med. 1995;23:196-202.
10.
10. Bosch U, Kasperczyk WJ. Healing of the patellar tendon autograft after posterior cruciate ligament reconstruction: a process of ligamentization? An experimental study in a sheep model. Am J Sports Med. 1992;20:558-566.
11.
11. Bowen-Pope DF, Malpass TW, Foster DM, et al.Platelet-derived growth factor in vivo: levels, activity, and rate of clearance. Blood. 1984;64:458-469.
12.
12. Claes L.Empfehlung für die mechanische Prüfung der Bandprothesen. Hefte zu der Unfallchirurg. 1996;234:205-210.
13.
13. Claes LE, Durselen L, Rubenacker S.Comparative investigation on the biomechanical properties of ligament replacement in the sheep knee using six different ligament prostheses. Clin Mater. 1994;15: 15-22.
14.
14. Clancy WG Jr, Narechania RG, Rosenberg TD, et al.Anterior and posterior cruciate ligament reconstruction in rhesus monkeys. J Bone Joint Surg Am. 1981;63:1270-1284.
15.
15. DesRosiers EA, Yahia L, Rivard CH. Proliferative and matrix synthesis response of canine anterior cruciate ligament fibroblasts submitted to combined growth factors. J Orthop Res. 1996;14:200-208.
16.
16. Ellis D.Cross-sectional area measurements for tendon specimens: a comparison of several methods. J Biomech. 1968;2:175-186.
17.
17. Frank CB, Jackson DW. The science of reconstruction of the anterior cruciate ligament. J Bone Joint Surg Am. 1997;79:1556-1576.
18.
18. Hannafin JA, Attia ET, Warren RF, et al.Characterization of chemotactic migration and growth kinetics of canine knee ligament fibroblasts. J Orthop Res. 1999;17:398-404.
19.
19. Hildebrand KA, Woo SL, Smith DW, et al.The effects of platelet-derived growth factor-BB on healing of the rabbit medial collateral ligament: an in vivo study. Am J Sports Med. 1998;26:549-554.
20.
20. Kasperczyk WJ, Bosch U, Oestern HJ, et al.Staging of patellar tendon autograft healing after posterior cruciate ligament reconstruction: a biomechanical and histological study in a sheep model. Clin Orthop. 1993;286:271-282.
21.
21. Kobayashi D, Kurosaka M, Yoshiya S, et al.Effect of basic fibroblast growth factor on the healing of defects in the canine anterior cruciate ligament [comments]. Knee Surg Sports Traumatol Arthrosc. 1997;5:189-194.
22.
22. Kuroda R, Kurosaka M, Yoshiya S, et al.Localization of growth factors in the reconstructed anterior cruciate ligament: immunohistological study in dogs. Knee Surg Sports Traumatol Arthrosc. 2000;8:120-126.
23.
23. Lambert KL. Vascularized patellar tendon graft with rigid internal fixation for anterior cruciate ligament insufficiency. Clin Orthop. 1983;172:85-89.
24.
24. Lattermann C, Baltzer AWA, Whalen JD, et al.Gene therapy in sports medicine. Sports Med Arthrosc Rev. 1998;6:83-88.
25.
25. Lee J, Green MH, Amiel D.Synergistic effect of growth factors on cell outgrowth from explants of rabbit anterior cruciate and medial collateral ligaments. J Orthop Res. 1995;13:435-441.
26.
26. Lee J, Harwood FL, Akeson WH, et al.Growth factor expression in healing rabbit medial collateral and anterior cruciate ligaments. Iowa Orthop J. 1998;18:19-25.
27.
27. Lepisto J, Laato M, Niinikoski J, et al.Effects of homodimeric iso-forms of platelet-derived growth factor (PDGF-AA and PDGF-BB) on wound healing in rat. J Surg Res. 1992;53:596-601.
28.
28. Letson AK, Dahners LE. The effect of combinations of growth factors on ligament healing. Clin Orthop. 1994;308:207-212.
29.
29. Lynch SE, de Castilla GR, Williams RC, et al.The effects of short-term application of a combination of platelet-derived and insulin-like growth factors on periodontal wound healing. J Periodontol. 1991;62:458-467.
30.
30. Lynch SE, Nixon JC, Colvin RB, et al.Role of platelet-derived growth factor in wound healing: synergistic effects with other growth factors. Proc Natl Acad Sci U S A. 1987;84:696-700.
31.
31. Marui T, Niyibizi C, Georgescu HI, et al.Effect of growth factors on matrix synthesis by ligament fibroblasts. J Orthop Res. 1997;15:18-23.
32.
32. McFarland EG, Morrey BF, An KN, et al.The relationship of vascularity and water content to tensile strength in a patellar tendon replacement of the anterior cruciate in dogs. Am J Sports Med. 1986;14:436-448.
33.
33. McGee GS, Davidson JM, Buckley A, et al.Recombinant basic fibroblast growth factor accelerates wound healing. J Surg Res. 1988;45:145-153.
34.
34. Menetrey J, Kasemkijwattana C, Day CS, et al.Direct-, fibroblast- and myoblast-mediated gene transfer to the anterior cruciate ligament. Tissue Eng. 1999;5:435-442.
35.
35. Nagineni CN, Amiel D, Green MH, et al.Characterization of the intrinsic properties of the anterior cruciate and medial collateral ligament cells: an in vitro cell culture study. J Orthop Res. 1992;10:465-475.
36.
36. Nakamura N, Shino K, Natsuume T, et al.Early biological effect of in vivo gene transfer of platelet-derived growth factor (PDGF)-B into healing patellar ligament. Gene Ther. 1998;5:1165-1170.
37.
37. Natsu-ume T, Nakamura N, Shino K, et al.Temporal and spatial expression of transforming growth factor-beta in the healing patellar ligament of the rat. J Orthop Res. 1997;15:837-843.
38.
38. Ng GY, Oakes BW, Deacon OW, et al.Biomechanics of patellar tendon autograft for reconstruction of the anterior cruciate ligament in the goat: three-year study. J Orthop Res. 1995;13:602-608.
39.
39. Ng GY, Oakes BW, Deacon OW, et al.Long-term study of the biochemistry and biomechanics of anterior cruciate ligament-patellar tendon autografts in goats. J Orthop Res. 1996;14:851-856.
40.
40. Panossian V, Liu SH, Lane JM, et al.Fibroblast growth factor and epidermal growth factor receptors in ligament healing. Clin Orthop. 1997;342:173-180.
41.
41. Pierce GF, Mustoe TA, Lingelbach J, et al.Platelet-derived growth factor and transforming growth factor-beta enhance tissue repair activities by unique mechanisms. J Cell Biol. 1989;109:429-440.
42.
42. Pierce GF, Vande Berg J, Rudolph R, et al.Platelet-derived growth factor-BB and transforming growth factor beta 1 selectively modulate glycosaminoglycans, collagen, and myofibroblasts in excisional wounds. Am J Pathol. 1991;138:629-646.
43.
43. Ross R, Raines EW, Bowen-Pope DF. The biology of platelet-derived growth factor. Cell. 1986;46:155-169.
44.
44. Scherping SC Jr, Schmidt CC, Georgescu HI, et al.Effect of growth factors on the proliferation of ligament fibroblasts from skeletally mature rabbits. Connect Tissue Res. 1997;36:1-8.
45.
45. Schmidmaier G, Wildemann B, Bail H, et al.Local application of growth factors (insulin-like growth factor-1 and transforming growth factor-beta1) from a biodegradable poly(D, L-lactide) coating of osteosynthetic implants accelerates fracture healing in rats. Bone. 2001;28:341-350.
46.
46. Schmidmaier G, Wildemann B, Stemberger A, et al.Biodegradable poly(D, L-lactide) coating of implants for continuous release of growth factors. J Biomed Mater Res. 2001;58:449-455.
47.
47. Schmidt CC, Georgescu HI, Kwoh CK, et al.Effect of growth factors on the proliferation of fibroblasts from the medial collateral and anterior cruciate ligaments. J Orthop Res. 1995;13:184-190.
48.
48. Spindler KP, Imro AK, Mayes CE, et al.Patellar tendon and anterior cruciate ligament have different mitogenic responses to platelet-derived growth factor and transforming growth factor beta. J Orthop Res. 1996;14:542-546.
49.
49. Unterhauser FN, Weiler A, Bail H, et al.Endoligamentous revascularization of a free soft tissue graft after ACL reconstruction. Paper presented at: 48th Annual Meeting of the Orthopaedic Research Society; February 2002; Dallas, Tex.
50.
50. Weiler A, Peine R, Pashmineh-Azar A, et al.Tendon healing in a bone tunnel, part I: biomechanical results after biodegradable interference fit fixation in a model of anterior cruciate ligament reconstruction in sheep. Arthroscopy. 2002;18:113-123.
51.
51. Weiler A, Peters G, Maurer J, et al.Biomechanical properties and vascularity of an anterior cruciate ligament graft can be predicted by contrast-enhanced magnetic resonance imaging: a two-year study in sheep. Am J Sports Med. 2001;29:751-761.
52.
52. Weiler A, Unterhauser FN, Bail H-J, et al.Alpha-smooth muscle actin is expressed by fibroblastic cells of the ovine anterior cruciate ligament and its free tendon graft during remodeling. J Orthop Res. 2002;20:310-317.
53.
53. Woo SL, Hildebrand K, Watanabe N, et al.Tissue engineering of ligament and tendon healing. Clin Orthop. 1999;367(suppl):S312-S323.
54.
54. Woo SL, Smith DW, Hildebrand KA, et al.Engineering the healing of the rabbit medial collateral ligament. Med Biol Eng Comput. 1998;36:359-364.
55.
55. Woo SL-Y, Suh J-K, Parsons IM, et al.Biologic intervention in ligament healing. Sports Med Arthrosc Rev. 1998;6:74-82.
56.
56. Yasuda K, Hayashi K.Remodeling of tendon graft in ligament reconstruction. In: Hayashi K, Kamiya A, Ono K, eds. Biomechanics: Functional Adaptation and Remodeling. Heidelberg, NY: Springer; 1997:213-250.
57.
57. Yoshida M, Fujii K.Differences in cellular properties and responses to growth factors between human ACL and MCL cells. J Orthop Sci. 1999;4:293-298.
