Regenerative Medicine: Effect of Treatment with Biphasic Cross-Linked Hyaluronic Acid in Osteochondral Lesions
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Published:
Aug 20, 2024
Keywords:
Hyaluronic acid, cartilage regeneration, osteochondral injury
Main Article Content
Abstract
Objective: To demonstrate whether treatment with biphasic cross-linked hyaluronic acid in osteochondral lesions promotes the regeneration of cartilage tissue.
Materials and Methods: Fifteen adult female rabbits were randomly assigned to three groups. G1 was the control group, whereas G2 and G3 underwent surgery to treat an osteochondral injury in the right knee (4mm diameter, 5mm depth). G3 received treatment with 0.2 ml of hyaluronic acid intrarticularly after surgery. Clinical, biochemical, histopathological controls and imaging studies were performed.
Results: Clinically, G3 exhibited less pain on palpation than G2 after 45 days. In G3, almost all samples showed evidence of cartilage tissue regeneration at the injury site, with neither bone edema or considerable joint effusion detected on MRI. The histological tests of G3 samples revealed an increase in the extracellular matrix of cartilaginous tissue when compared to G2, with hypercellularity caused by chondrocytes that formed axial and coronal isogenic groups.
Conclusions: This study provides evidence that treatment with biphasic cross-linked hyaluronic acid in experimental units of rabbits with osteochondral injuries did not cause pain in the early stages of the injury. In turn, imaging and histopathological studies revealed that the injured tissue had been repaired.
Materials and Methods: Fifteen adult female rabbits were randomly assigned to three groups. G1 was the control group, whereas G2 and G3 underwent surgery to treat an osteochondral injury in the right knee (4mm diameter, 5mm depth). G3 received treatment with 0.2 ml of hyaluronic acid intrarticularly after surgery. Clinical, biochemical, histopathological controls and imaging studies were performed.
Results: Clinically, G3 exhibited less pain on palpation than G2 after 45 days. In G3, almost all samples showed evidence of cartilage tissue regeneration at the injury site, with neither bone edema or considerable joint effusion detected on MRI. The histological tests of G3 samples revealed an increase in the extracellular matrix of cartilaginous tissue when compared to G2, with hypercellularity caused by chondrocytes that formed axial and coronal isogenic groups.
Conclusions: This study provides evidence that treatment with biphasic cross-linked hyaluronic acid in experimental units of rabbits with osteochondral injuries did not cause pain in the early stages of the injury. In turn, imaging and histopathological studies revealed that the injured tissue had been repaired.
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Álvarez, J. L., Francioni , N., Operti, C., Orellana , M. F., Santiago , O., Sarrio, L., Stur, M., Mardegan Issa , J. P., Fonseca, S., & Feldman, S. (2024). Regenerative Medicine: Effect of Treatment with Biphasic Cross-Linked Hyaluronic Acid in Osteochondral Lesions. Revista De La Asociación Argentina De Ortopedia Y Traumatología, 89(4), 374-384. https://doi.org/10.15417/issn.1852-7434.2024.89.4.1871
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subchondral bone. Knee Surg Sports Traumatol Arthrosc 2010;18(4):448-62.
https://doi.org/10.1007/s00167-010-1052-1
8. Bravo Molina B, Forriol F, Álvarez Lozano E. Regenerar el cartílago articular: perspectivas y futuro. Rev Esp
Artrosc Cir Articul 2021;28(1):51-62. Disponible en: https://fondoscience.com/sites/default/files/articles/pdf/
reaca.28171.fs1911064-regenerar-cartilago-articular-perspectivas-futuro.pdf
9. Savage-Elliott I, Ross KA, Smyth NA, Murawski CD, Kennedy JG. Osteochondral lesions of the talus:
a current concepts review and evidence-based treatment paradigm. Foot Ankle Spec 2014;7(5):414-22.
https://doi.org/10.1177/1938640014543362
10. Meyer K, Palmer J. The polysaccharide of the vitreous humor. J Biol Chem 1934;107(3):629-34.
https://doi.org/10.1016/S0021-9258(18)75338-6
11. García-Fuentes M, Meinel AJ, Hilbe M, Meinel L, Merkle HP. Silk fibroin/hyaluronan scaffolds for human
mesenchymal stem cell culture in tissue engineering. Biomaterials 2009;30(28):5068-76.
https://doi.org/10.1016/j.biomaterials.2009.06.008
12. Salter DM, Godolphin JL, Gourlay MS, Lawson MF, Hughes DE, Dunne E. Analysis of human articular
chondrocyte CD44 isoform expression and function in health and disease. J Pathol 1996;179(4):396-402.
https://doi.org/10.1002/ (SICI) 1096-9896(199608)179:4<396: AID-PATH606>3.0.CO; 2-G
13. Knudson CB, Knudson W. Hyaluronan and CD44: modulators of chondrocyte metabolism. Clin Orthop Relat Res 2004;(427 Suppl):S152-62. PMID: 15480059
14. Arnold W, Fullerton DS, Holder S, May CS. Viscosupplementation: managed care issue for osteoarthritis of the
knee. J Manag Care Pharm 2007;13(4):S3-19. https://doi.org/10.18553/jmcp.2007.13.s4.3
15. Volpi N, Schiller J, Stern R, Soltés L. Role, metabolism, chemical modifications and applications of hyaluronan.
Curr Med Chem 2009;16(14):1718-45. https://doi.org/10.2174/092986709788186138
16. Peck J, Slovek A, Miro P, Vij N, Traube B, Lee C, et al. A comprehensive review of viscosupplementation in
osteoarthritis of the knee. Orthop Rev (Pavia) 2021;13(2):25549. https://doi.org/10.52965/001c.25549
17. Marshall KW. Intra-articular hyaluronan therapy. Curr Opin Rheumatol 2000;12(5):468-74.
https://doi.org/10.1097/00002281-200009000-00022
18. Pereira H, Sousa DA, Cunha A, Andrade R, Espregueira-Mendes J, Oliveira JM, et al. Hyaluronic acid. Adv Exp
Med Biol 2018;1059:137-53. https://doi.org/10.1007/978-3-319-76735-2_6
19. Roemer FW, Guermazi A, Demehri S, Wirth W, Kijowski R. Imaging in osteoarthritis. Osteoarthritis Cartilage
2022;30(7):913-934. https://doi.org/10.1016/j.joca.2021.04.018
20. Figueroa D, Calvo R, Vaisman A, Carrasco MA, Moraga C, Delgado I. Knee chondral lesions: incidence and
correlation between arthroscopic and magnetic resonance findings. Arthroscopy 2007;23(3):312-5.
https://doi.org/10.1016/j.arthro.2006.11.015
21. Sifre V, Ten-Esteve A, Serra CI, Soler C, Alberich-Bayarri Á, Segarra S, et al. Knee cartilage and subcondral bone evaluations by magnetic resonance imaging correlate with histological biomarkers in an osteoarthritis rabbit model. Cartilage 2022;13(3):19476035221118166. https://doi.org/10.1177/19476035221118166
22. D’Ambrosi R, Maccario C, Ursino C, Serra N, Usuelli FG. The role of bone marrow edema on osteochondral
lesions of the talus. Foot Ankle Surg 2018;24(3):229-35. https://doi.org/10.1016/j.fas.2017.02.010
23. Ahn J, Choi JG, Jeong BO. Clinical outcomes after arthroscopic microfracture for osteochondral lesions of the talus are better in patients with decreased postoperative subchondral bone marrow edema. Knee Surg Sports Traumatol Arthrosc 2021;29(5):1570-6. https://doi.org/10.1007/s00167-020-06303-y
24. Roemer FW, Guermazi A, Felson DT, Niu J, Nevitt MC, Crema MD, et al. Presence of MRI-detected joint effusion
and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST
study. Ann Rheum Dis 2011;70(10):1804-9. https://doi.org/10.1136/ard.2011.150243.
25. Wang X, Blizzard L, Jin X, Chen Z, Zhu Z, Han W, et al. Quantitative assessment of knee effusion-synovitis in older adults: Association with knee structural abnormalities. Arthritis Rheumatol 2016;68(4):837-44.
https://doi.org/10.1002/art.39526
26. Kleemann RU, Krocker D, Cedraro A, Tuischer J, Duda GN. Altered cartilage mechanics and histology in knee
osteoarthritis: relation to clinical assessment (ICRS Grade). Osteoarthritis Cartilage 2005;13(11):958-63.
https://doi.org/10.1016/j.joca.2005.06.008
27. Huey DJ, Hu JC, Athanasiou KA. Unlike bone, cartilage regeneration remains elusive. Science 2012;338(6109):917-21. https://doi.org/10.1126/science.1222454
28. Legré-Boyer V. Viscosupplementation: techniques, indications, results. Orthop Traumatol Surg Res 2015;101(1
Suppl):S101-8. https://doi.org/10.1016/j.otsr.2014.07.027
29. Montarele LF, Pitol DL, Fiorelini Pereira B, Feldman S, Sassoli Fazan VP, Mardegan Issa JP. Histological and
immunohistochemical analysis of the effects of topical melatonin treatment associated with collagen sponge and
rhBMP-2 protein on bone remodeling. Biomolecules 2022;12(12):1738. https://doi.org/10.3390/biom12121738
30. Salamanna F, Giavaresi G, Parrilli A, Martini L, Nicoli Aldini N, Abatangelo G, et al. Effects of intra-articular
hyaluronic acid associated to Chitlac (arty-duo®) in a rat knee osteoarthritis model. J Orthop Res 2019;37(4):867-
876. https://doi.org/10.1002/jor.24259
31. Cardoneanu A, Macovei LA, Burlui AM, Mihai IR, Bratoiu I, Rezus II, et al. Temporomandibular joint
osteoarthritis: Pathogenic mechanisms involving the cartilage and subchondral bone, and potential therapeutic
strategies for joint regeneration. Int J Mol Sci 2022;24(1):171. https://doi.org/10.3390/ijms24010171
32. Park YB, Ha CW, Lee CH, Yoon YC, Park YG. Cartilage regeneration in osteoarthritic patients by a composite of
allogeneic umbilical cord blood-derived mesenchymal stem cells and hyaluronate hydrogel: Results from a clinical trial for safety and proof-of-concept with 7 years of extended follow-up. Stem Cells Transl Med 2017;6(2):613-21. https://doi.org/10.5966/sctm.2016-0157
33. KhaliliJafarabad N, Behnamghader A, Khorasani MT, Mozafari M. Platelet-rich plasma-hyaluronic acid/chondrotin sulfate/carboxymethyl chitosan hydrogel for cartilage regeneration. Biotechnol Appl Biochem 2022;69(2):534-47. https://doi.org/10.1002/bab.2130
34. Gümüş N, Acaban MB, Demirbağ HO. Hyaluronic acid dermal filler promotes cartilage reshaping in rabbit ears. Aesthetic Plast Surg 2022;46(4):1932-41. https://doi.org/10.1007/s00266-022-02873-z
35. Ozkan FU, Uzer G, Türkmen I, Yildiz Y, Senol S, Ozkan K, et al. Intra-articular hyaluronate, tenoxicam and vitamin E in a rat model of osteoarthritis: evaluation and comparison of chondroprotective efficacy. Int J Clin Exp Med 2015;8(1):1018-26. PMID: 25785088
36. Vitello Xavier M, Farez N, Salvatierra PL, Jardini AL, Kharmandayan P, Feldman S. Biological performance of
a bioabsorbable Poly (L-Lactic Acid) produced in polymerization unit: in vivo studies. F1000Res 2021;10:1275.
https://doi.org/10.12688/f1000research.73754.1
37. Paulini M, Camal Ruggieri IN, Ramallo M, Alonso M, Rodriguez-Cabello JC, Esbrit P, et al. Recombinant proteinsbased strategies in bone tissue engineering. Biomolecules 2021;12(1):3. https://doi.org/10.3390/biom12010003
38. Mardegan Issa JP, dos Santos Neto OM, Macedo AP, Gonçalves Gonzaga M, Lara Pereira YC, Feldman S.
Evaluation of tissue in repair with natural latex and/or hyaluronic acid in surgical bone defects. Braz Dent J 2021;32(4):83-95. https://doi.org/10.1590/0103-6440202104302
39. Ramallo M, Carreras-Sánchez I, López-Fernández A, Vélez R, Aguirre M, Feldman S, et al. Advances in
translational orthopedic research with species-specific multipotent mesenchymal stromal cells derived from the
umbilical cord. Preclinical research with MSCs from the umbilical cord. Histol Histopathol 2021;36(1):19-30.
https://doi.org/10.14670/HH-18-249
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