Autogenous Osteochondral Graft Associated with IGF-1 in Induced Articular Cartilage Lesion in Rabbits

Authors

  • Fernando Yoiti Kitamura Kawamoto Departamento de Medicina Veterinária, Universidade Federal de Lavras (UFLA), Lavras, MG, Brazil.
  • Leonardo Augusto Lopes Muzzi Departamento de Medicina Veterinária, Universidade Federal de Lavras (UFLA), Lavras, MG, Brazil.
  • Antônio Carlos Cunha Lacreta Junior Departamento de Medicina Veterinária, Universidade Federal de Lavras (UFLA), Lavras, MG, Brazil.
  • Djeison Lutier Raymundo Departamento de Medicina Veterinária, Universidade Federal de Lavras (UFLA), Lavras, MG, Brazil.
  • Rodrigo Gabellini Leonel Alves Departamento de Medicina Veterinária, Universidade de Uberaba (UNIUBE), Uberaba, MG.
  • Willer Guimarães e Silva Departamento de Medicina Veterinária, Universidade Federal de Lavras (UFLA), Lavras, MG, Brazil.
  • Ruthnéa Aparecida Lázaro Muzzi Departamento de Medicina Veterinária, Universidade Federal de Lavras (UFLA), Lavras, MG, Brazil.

DOI:

https://doi.org/10.22456/1679-9216.87212

Abstract

Background: Articular cartilage has a limited capacity for regeneration and of the various treatments proposed, none have reached appropriate therapeutic effectiveness. This study aimed to evaluate autogenous osteochondral grafts in intact or macerated format, in association with or without insulin-like growth factor type-1 (IGF-1) in the repair of osteochondral defects induced in the femoral trochlear groove of rabbits.

Materials, Methods & Results: Seventeen healthy White New Zealand rabbits were selected for this study. The rabbits were female, six months old, and had an average body weight of 4.5 kg. All 34 stifle joints were subjected to autogenous osteochondral grafting in the femoral trochlear groove. The joints were divided into four groups designated as intact osteochondral graft with IGF-1 (INT + IGF), intact osteochondral graft with physiological solution (INT + FIS), macerated osteochondral graft with IGF-1 (MAC + IGF), and macerated osteochondral graft with physiological solution (MAC + FIS). Serial evaluations were performed by orthopedic and radiographic examination. After 6 and 12 weeks postoperatively, the grafted area was subjected to macroscopic, histological, and immunohistochemical analyses. Although no statistically significant differences were found between the groups in relation to clinical, macroscopic, histological, and immunohistochemical aspects, a tendency of IGF-1 to promote tissue repair was evident. In the radiographic evaluation, the articular surface and the recipient site in both groups with IGF-1 showed significantly more effective filling (P ≤ 0.05). Regardless of the group, collagen type 2 production, as assessed by immunohistochemistry, was found to be appropriate on the grafted articular surface.

Discussion: In extensive cartilage lesions, the use of intact osteochondral grafts may be infeasible due to donor site morbidity. An alternative is the use of macerated osteochondral grafts, which cover a larger area and act as a support and cellular source in the repair process. Growth factors have been evaluated in association with grafted tissues to aid tissue repair, and IGF-1 is currently prominent. In the radiographic analysis of the present study, when comparing sites subjected to osteochondral grafting, presence of the whole graft evidenced adequate local filling in all groups. However, graft integration was apparently rapid and effective in the INT + IGF and MAC + IGF groups from the sixth and ninth weeks of the procedure, respectively. In the macroscopic evaluation at the twelfth week, graft integration with the original cartilaginous tissue was more evident, especially in both groups treated with IGF-1. It is likely that the property of IGF-1 to increase chondrogenesis in the cartilage repair of articular lesions in vivo may have contributed to these results in radiographic and macroscopic examinations. Histological examination showed no significant difference between groups in the same period of time; however, it was observed that addition of IGF-1 promoted a more evident tissue reaction and cellular activation, potentiating the process of reabsorption and repair in the grafted tissue. Immunohistochemical analysis showed similar immunoreactivity for collagen type 2 in all groups as early as the sixth week. However, a small portion of these tissues cannot be considered true hyaline cartilage due to the absence of some typical features. In summary, addition of IGF-1 to the autogenous osteochondral graft seemed to stimulate reabsorption and replacement processes in the grafted tissue. The grafts showed adequate ability to repair articular cartilage, displaying formation of collagen type 2 similar to that in the original tissue.

Downloads

Download data is not yet available.

References

Clark A., Milbrandt T.A., Hilt J.Z. & Puleo D.A. 2014. Retention of insulin-like growth factor I bioactivity during the fabrication of sintered polymeric scaffolds. Biomedical Materials. 9(2): 1-8.

Cotter E.J., Wang K.C., Yanke A.B. & Chubinskaya S. 2018. Bone marrow aspirate concentrate for cartilage defects of the knee: from bench to bedside evidence. Cartilage. 9(2): 161-170.

Fitzpatrick N., Van Terheijden C., Yeadon R. & Smith T.J. 2010. Osteochondral autograft transfer for treatment of osteochondritis dissecans of the caudocentral humeral head in dogs. Veterinary Surgery. 39(8): 925-935.

Gugjoo M.B., Amarpal, Abdelbaset-Ismail A., Aithal H.P., Kinjavdekar P., Pawde A.M., Kumar G.S. & Sharma G.T. 2017. Mesenchymal stem cells with IGF-1 and TGF- 1 in laminin gel for osteochondral defects in rabbits. Biomedicine & Pharmacotherapy. 93: 1165-1174.

Jakob R.P., Franz T., Gautier E. & Mainil-Varlet P. 2002. Autologous osteochondral grafting in the knee: indication,

results, and reflections. Clinical Orthopaedics and Related Research. 1(401): 170-184.

Kim K., Lam J., Lu S., Spicer P.P., Lueckgen A, Tabata Y, Wong M.E., Jansen J.A., Mikos A.G. & Kasper F.K. 2013. Osteochondral tissue regeneration using a bilayered composite hydrogel with modulating dual growth factor release kinetics in a rabbit model. Journal of Controlled Release. 168(2): 166-178.

Krusche-Mandl I., Schmitt B., Zak L., Apprich S., Aldrian S., Juras V., Friedrich K.M., Marlovits S., Weber M. & Trattnig S. 2012. Long-term results 8 years after autologous osteochondral transplantation: 7T gagCEST and sodium magnetic resonance imaging with morphological and clinical correlation. Osteoarthritis and Cartilage. 20(5): 357-363.

Liu S., Wu J., Liu X, Chen D., Bowlin G.L., Cao L., Lu J., Li F., Mo X. & Fan C. 2015. Osteochondral regeneration using an oriented nanofiber yarn-collagen type I/hyaluronate hybrid/TCP biphasic scaffold. Journal of Biomedical Materials Research. Part A. 103(2): 581-592.

Loffredo F.S., Pancoast J.R., Cai L., Vannelli T., Dong J.Z., Lee R.T. & Patwari P. 2014. Targeted delivery to cartilage is critical for in vivo efficacy of insulin-like growth factor 1 in a rat model of osteoarthritis. Arthritis & Rheumatology. 66(5): 1247-1255.

Lu Y., Dhanaraj S., Wang Z., Bradley D.M., Bowman S.M., Cole B.J. & Binette F. 2006. Minced cartilage without cell culture serves as an effective intraoperative cell source for cartilage repair. Journal of Orthopaedic Research. 24(6): 1261-1270.

Madry H., Kaul G., Cucchiarini M., Stein U., Zurakowski D., Remberger K., Menger M.D., Kohn D. & Trippel S.B. 2005. Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulinlike growth factor I (IGF-I). Gene Therapy. 12(15): 1171-1179.

Madry H., Orth P., Kaul G., Zurakowski D., Menger M.D., Kohn D. & Cucchiarini M. 2010. Acceleration of articular cartilage repair by combined gene transfer of human insulin-like growth factor I and fibroblast growth factor-2 in vivo. Archives of Orthopaedic and Trauma Surgery. 130(10): 1311-1322.

Marmotti A., Bruzzone M., Bonasia D.E., Castoldi F., Rossi R., Piras L., Maiello A., Realmuto C. & Peretti G.M. 2012. One-Step osteochondral repair with cartilage fragments in a composite scaffold. Knee Surgery, Sports Traumatology, Arthroscopy. 20(12): 2590-2601.

Maruyama M., Satake H., Suzuki T., Honma R., Naganuma Y., Takakubo Y. & Takagi M. 2017. Comparison of the effects of osteochondral autograft transplantation with platelet-rich plasma or platelet-rich fibrin on osteochondral defects in a rabbit model. The American Journal of Sports Medicine. 45(14): 3280-3288.

Morisset S., Frisbie D.D., Robbins P.D., Nixon A.J. & McIlwraith C.W. 2007. IL-1ra/IGF-1 gene therapy modulates repair of microfractured chondral defects. Clinical Orthopaedics and Related Research. 462: 221-228.

Nixon A.J., Fortier L.A., Williams J. & Mohammed H. 1999. Enhanced repair of extensive articular defects by insulin-like growth factor-I-laden fibrin composites. Journal of Orthopaedic Research. 17(4): 475-487.

Orth P., Kaul G., Cucchiarini M., Zurakowski D., Menger M.D., Kohn D. & Madry H. 2011. Transplanted articular chondrocytes co-overexpressing IGF-I and FGF-2 stimulate cartilage repair in vivo. Knee Surgery, Sports Traumatology, Arthroscopy. 19(12): 2119-2130.

Rodríguez-Merchán E.C. 2012. The treatment of cartilage defects in the knee joint: microfracture, mosaicoplasty, and

autologous chondrocyte implantation. American Journal of Orthopedics. 41(5): 236-239.

Sellers R.S., Peluso D. & Morris E.A. 1997. The effect of Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2)

on the healing of full-thickness defects of articular cartilage. The Journal of Bone and Joint Surgery. American Volume. 79(10): 1452-1463.

Singh N.K., Singh G.R., Amarpal, Kinjavdekar P., Sharma A.K., Mohanty T.R., Kumar S., Chae H.S., Yoo Y.M. & Ahn C.N. 2007. Articular cartilage repair with autografting under the influence of insulin-like growth factor-1 in rabbits. Journal of Veterinary Medicine. A, Physiology, Pathology, Clinical Medicine. 54(4): 210-218.

Singh N.K., Singh G.R., Jeong D.K. & Lee S.J. 2013. Healing of full-thickness articular cartilage defects treated with cultured autologous chondrogenic satellite cells isolated from chondral stem cell niche in rabbits. Journal of Surgical Research. 183(2): 629-638.

Tiwary R., Pal A., Aithal H.P., Kinjavdekar P., Pawde A.M. & Singh R. 2013. Effect of IGF-1 and uncultured autologous

bone-marrow-derived mononuclear cells on repair of osteochondral defect in rabbits. Cartilage. 5(1): 43-54.

Wakitani S., Goto T., Pineda S.J., Young R.G., Mansour J.M., Caplan A.I. & Goldberg V.M. 1994. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. The Journal of Bone Joint Surgery. American Volume. 76(4): 579-592.

Walczak B.E., Nies M.S., Trask D.J., Hetzel S., Roney P.J., Squire M.W. & Baer G.S. 2018. Osteochondral graft size is significantly associated with increased force and decreased chondrocyte viability. The American Journal of Sports Medicine. 46(3): 623-631.

Zhang Z., Li L., Yang W., Cao Y., Shi Y., Li X. & Zhang Q. 2017. The effects of different doses of IGF-1 on cartilage and subchondral bone during the repair of full-thickness articular cartilage defects in rabbits. Osteoarthritis and Cartilage. 25(2): 309-320.

Published

2018-01-01

How to Cite

Kawamoto, F. Y. K., Muzzi, L. A. L., Lacreta Junior, A. C. C., Raymundo, D. L., Alves, R. G. L., Guimarães e Silva, W., & Lázaro Muzzi, R. A. (2018). Autogenous Osteochondral Graft Associated with IGF-1 in Induced Articular Cartilage Lesion in Rabbits. Acta Scientiae Veterinariae, 46(1), 10. https://doi.org/10.22456/1679-9216.87212

Issue

Section

Articles

Most read articles by the same author(s)

1 2 3 > >>