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Journals / Manas Journal of Agriculture Veterinary and Life Sciences / 2026 / Cilt: 16 Sayı: 1

Evaluation of Cytotoxicity and Genotoxicity af An Intra-Articular Hyaluronic Acid Gel Implant by Some In Vitro Biocompatibility Tests.

Bir İntra Artiküler Hiyalüronik Asit Jel İmplantın Bazı İn Vitro Biyouyumluluk Testleri ile Sitotoksisitesinin ve Genotoksisitesinin Değerlendirilmesi

Yasin Ozkabadayı(Kırıkkale Üniversitesi Veteriner Fakültesi Histoloji-Embriyoloji Anabilim Dalı)0000-0003-0326-3407
Rümeysa Çelik(KIRIKKALE ÜNİVERSİTESİ, SAĞLIK BİLİMLERİ ENSTİTÜSÜ, VETERİNER HİSTOLOJİ-EMBRİYOLOJİ (DR))0009-0006-4089-8793
Yasemin Sezgin(KIRIKKALE ÜNİVERSİTESİ, VETERİNER FAKÜLTESİ, HASTALIKLAR VE KLİNİK BİLİMLERİ BÖLÜMÜ, VETERİNERLİK FARMAKOLOJİ VE TOKSİKOLOJİSİ ANABİLİM DALI)0009-0006-7119-3200
Pages
74–83
Publication Date
2026-06-23
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Therefore, when selecting tests and evaluating results, it is recommended to consider the physical and chemical properties of the sample and to apply both direct and indirect cytotoxicity tests when necessary.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:The first step in testing the biocompatibility of medical devices is cytotoxicity testing.
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Key Findings & Data:In the MTT test, cell viability at a 1:1 concentration was 52.41% and 3.44%, indicating that the sample was cytotoxic.
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Conclusion & Impact:Therefore, when selecting tests and evaluating results, it is recommended to consider the physical and chemical properties of the sample and to apply both direct and indirect cytotoxicity tests when necessary.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:Biyouyumluluk · sitotoksisite · genotoksisite

Abstract

The first step in testing the biocompatibility of medical devices is cytotoxicity testing. Genotoxicity tests, another important aspect of biocompatibility risk assessment, are also performed to analyze carcinogenic, mutagenic, and genital toxicity. Subjecting medical devices to a series of tests, such as cytotoxicity and genotoxicity tests, before clinical use is a necessity for both risk assessment and the licensing process. In this study, the cytotoxicity of a newly produced commercial medical device based on hyaluronic acid was evaluated using MTT and agar diffusion tests, and its genotoxicity was evaluated using the in vitro micronucleus test. In the MTT test, cell viability at a 1:1 concentration was 52.41% and 3.44%, indicating that the sample was cytotoxic. In the agar diffusion test, there was no reaction in the cells to which the sample was applied, and the result was grade=0, indicating that it was not cytotoxic. In the in vitro micronucleus test, statistical calculations showed that the sample was not genotoxic. Direct cytotoxicity testing of viscous/gel-like samples may lead to false positive or false negative results. Therefore, when selecting tests and evaluating results, it is recommended to consider the physical and chemical properties of the sample and to apply both direct and indirect cytotoxicity tests when necessary. In conclusion, to accurately evaluate the results of biocompatibility tests, tests appropriate to the sample must be selected.

Özet

Tıbbi cihazların biyouyumluluğunu test etmenin ilk adımı sitotoksisite testidir. Biyouyumluluk risk değerlendirmesinin önemli bir ayağı olan genotoksisite testleri de karsinojenite, mutajenite ve genital toksisiteyi analiz etmek için yapılır. Tıbbi cihazların klinik kullanım öncesinde biyouyumluluk testlerine tabii tutulması hem risk değerlendirmesi hem de ruhsatlandırma süreci için bir zorunluluktur. Bu çalışmada, hiyalüronik asit bazlı yeni üretilen ticari bir tıbbi cihazın MTT testi ve agar difüzyon testleri ile sitotoksisitesi, in vitro mikronükleus testi ile de genotoksisitesi değerlendirildi. MTT testinde 1/1 konsantrasyonda hücre canlılığı %52,41 ± 3,44 olup numune sitotoksik olarak değerlendiridi. Agar difüzyon testinde ise numunenin uygulandığı hücrelerde reaksiyon yok ve derece=0 sonucuyla sitotoksik olmadığı belirlendi. İn vitro mikronükleus testinde ise istatistiksel hesaplamalar sonucunda numunenin genotoksik olmadığı gözlendi. Bu çalışma, sitotoksisite testlerinin sonuçlarında bir farklılık olduğunu göstermektedir. Bu farklılığın nedenleri, jel benzeri test örneğinin kimyasal bileşiminden ziyade fiziksel özelliklerinin, test ortamındaki hücre davranışını ve hücre zarının yüzey özelliklerini etkilemesinden kaynaklanmaktadır. Bu nedenle, biyouyumluluk testleri seçilirken ve sonuçlar değerlendirilirken, test örneğinin fiziksel ve kimyasal özelliklerinin dikkate alınması ve gerektiğinde hem doğrudan hem de dolaylı sitotoksisite testleri yapılarak örnek için uygun testlerin seçilmesi önerilir.

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Cite This Article

Ozkabadayı, Y., Çelik, R., Sezgin, Y. (2026). Evaluation of Cytotoxicity and Genotoxicity af An Intra-Articular Hyaluronic Acid Gel Implant by Some In Vitro Biocompatibility Tests.. Manas Journal of Agriculture Veterinary and Life Sciences, Cilt: 16 Sayı: 1, 74–83. https://doi.org/10.53518/mjavl.1869207

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References (41)

  1. Alexander, L. A., Denisov, L. N., Zotkin, E. G., Dydykina, I. S., Kochish, A. Y., Rodionova, S. S.,. & Gallelli, L. (2021). Pharmacological management of osteoarthritis with a focus on symptomatic slow-acting drugs: Recommendations from leading Russian experts. JCR: Journal of Clinical Rheumatology, 27(8), e533-e539.
  2. Bannuru, R. R., Osani, M. C., Vaysbrot, E. E., Arden, N. K., Bennell, K., Bierma-Zeinstra, S. M. A.,. & McAlindon, T. E. (2019). OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis and cartilage, 27(11), 1578-1589.
  3. Black, J. (2005). Biological performance of materials: fundamentals of biocompatibility. Crc Press.
  4. Bodo, M. A. R. I. A., Pezzetti, F., Baroni, T., Carinci, F., Arena, N., Nicoletti, I., & Becchetti, E. (1993). Hyaluronic acid modulates growth, morphology and cytoskeleton in embryonic chick skin fibroblasts. The International journal of developmental biology, 37(2), 349-352.
  5. Boeckel, R. S. A. Shinkai, M. L. Grossi, ve E. R. Teixeira, “In vitro evaluation of cytotoxicity of hyaluronic acid as an extracellular matrix on OFCOL II cells by the MTT assay”, Oral Surg Oral Med Oral Pathol Oral Radiol, c. 117, sy 6, ss. e423-e428, Haz. 2014, doi: 10.1016/j.oooo.2012.07.486.
  6. Conrozier, T., Raman, R., Diraçoglu, D., Montfort, J., Bard, H., Baron, D.,. & Henrotin, Y. (2024). EUROVISCO consensus guidelines for the use of hyaluronic acid viscosupplementation in knee osteoarthritis based on patient characteristics. Cartilage, 19476035241271970.
  7. De Tollenaere, M., Corriou, A., Durduret, A., Bernheim-Dennery, M., Haupt, T., Natsch, A.,. & Reynaud, R. (2025). In Vitro and Ex Vivo Investigations on the Tolerance and Safety of a 3 kDa Sodium Hyaluronate for Topical Application. Cosmetics, 12(6), 266.
  8. Gibbs, A. J., Gray, B., Wallis, J. A., Taylor, N. F., Kemp, J. L., Hunter, D. J., & Barton, C. J. (2023). Recommendations for the management of hip and knee osteoarthritis: a systematic review of clinical practice guidelines. Osteoarthritis and cartilage, 31(10), 1280-1292.
  9. Glinkowski, W. M., & Tomaszewski, W. (2025). Intra-articular hyaluronic acid for knee osteoarthritis: a systematic umbrella review. Journal of Clinical Medicine, 14(4), 1272.
  10. Glinkowski, W., Śladowski, D., Tomaszewski, W., & Pol-IAHA Study Group. (2025). Molecular mechanisms and therapeutic role of Intra-Articular hyaluronic acid in osteoarthritis: a precision Medicine perspective. Journal of Clinical Medicine, 14(8), 2547.
  11. Gundarov, V. P. (2003). Standardization and testing of medical devices. Meditsinskaia Tekhnika, (1), 44-51.
  12. Harvima, I. T., Heikura, H., Hyttinen, M., & Naukkarinen, A. (2006). Hyaluronic acid inhibits the adherence and growth of monolayer keratinocytes but does not affect the growth of keratinocyte epithelium. Archives of dermatological research, 298(5), 207-219.
  13. Hayashi, D., Roemer, F.W., Jarraya, M., Guermazi, A. (2025). Imaging of Osteoarthritis. In: Medical Radiology(). Springer, Berlin, Heidelberg. https://doi.org/10.1007/174_2024_516
  14. ISO 10993-1: 2018, Biological evaluation of medical devices—Part 1: Evaluation and testing within a risk management process.
  15. ISO, E. (2014). 10993-3: 2014: Biological Evaluation of Medical Devices—Part 3: Tests for Genotoxicity. Carcinogenicity and Reproductive Toxicity.
  16. Iso, I. S. O. (2009). 10993–5: 2009 Biological evaluation of medical devices—part 5: tests for in vitro cytotoxicity. International Organization for Standardization, Geneva, 34.
  17. Jorge, J. H., Giampaolo, E. T., Vergani, C. E., Machado, A. L., Pavarina, A. C., & Carlos, I. Z. (2004). Cytotoxicity of denture base resins: effect of water bath and microwave postpolymerization heat treatments. The Journal of Prosthetic Dentistry, 92(6), 568.
  18. Kawasaki, K., Ochi, M., Uchio, Y., Adachi, N., & Matsusaki, M. (1999). Hyaluronic acid enhances proliferation and chondroitin sulfate synthesis in cultured chondrocytes embedded in collagen gels. Journal of cellular physiology, 179(2), 142-148.
  19. Kolasinski, S. L., Neogi, T., Hochberg, M. C., Oatis, C., Guyatt, G., Block, J.,. & Reston, J. (2020). 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis & rheumatology, 72(2), 220-233.
  20. Kucharz, E. J., Szántó, S., Ivanova Goycheva, M., Petronijević, M., Šimnovec, K., Domżalski, M.,. & Reginster, J. Y. (2019). Endorsement by Central European experts of the revised ESCEO algorithm for the management of knee osteoarthritis. Rheumatology International, 39(7), 1117-1123.
  21. Li, W., Zhou, J., & Xu, Y. (2015). Study of the in vitro cytotoxicity testing of medical devices. Biomedical reports, 3(5), 617-620.
  22. Liu, Y. Yin, K. Yao, D. Ma, L. Cui, ve Y. Cao, “Influence of the concentrations of hyaluronic acid on the properties and biocompatibility of Cs-Gel-HA membranes”, Biomaterials, c. 25, sy 17, ss. 3523-3530, Ağu. 2004, doi: 10.1016/j.biomaterials.2003.09.102.
  23. Ong, K. L., Runa, M., Lau, E., & Altman, R. (2019). Is intra-articular injection of synvisc associated with a delay to knee arthroplasty in patients with knee osteoarthritis?. Cartilage, 10(4), 423-431.
  24. Phillips, M., Bhandari, M., Grant, J., Bedi, A., Trojian, T., Johnson, A., & Schemitsch, E. (2021). A systematic review of current clinical practice guidelines on intra-articular hyaluronic acid, corticosteroid, and platelet-rich plasma injection for knee osteoarthritis: an international perspective. Orthopaedic journal of sports medicine, 9(8), 23259671211030272.
  25. Ranawat, A., Guo, K., Phillips, M., Guo, A., Niazi, F., Bhandari, M., & Waterman, B. (2024). Health economic assessments of hyaluronic acid treatments for knee osteoarthritis: A systematic review. Advances in Therapy, 41(1), 65-81.
  26. Shanmugam, P. S. T., Sampath, T., Jagadeeswaran, I., Thamizharasan, S., & Fathima, S. (2023). Cytotoxicity. In Biocompatibility Protocols for Medical Devices and Materials (pp. 1-18). Academic Press.
  27. Soenen, S. J., Manshian, B., Montenegro, J. M., Amin, F., Meermann, B., Thiron, T.,. & Braeckmans, K. (2012). Cytotoxic effects of gold nanoparticles: a multiparametric study. ACS nano, 6(7), 5767-5783.
  28. Steinmetz, J. D., Culbreth, G. T., Haile, L. M., Rafferty, Q., Lo, J., Fukutaki, K. G.,. & Singh, S. (2023). Global, regional, and national burden of osteoarthritis, 1990–2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet Rheumatology, 5(9), e508-e522.
  29. Tomaszewski, W. (2016). Osteoarthritis–How to Treat to Slow its Progress. Ortopedia, Traumatologia, Rehabilitacja, 18(1), 91-97.
  30. Wiig, M., & ABRAHAMSSON, S. O. (2000). Hyaluronic acid modulates cell proliferation unequally in intrasynovial and extrasynovial rabbit tendons in vitro. The Journal of Hand Surgery: British & European Volume, 25(2), 183-187.
  31. Yao, Q., Wu, X., Tao, C., Gong, W., Chen, M., Qu, M.,. & Xiao, G. (2023). Osteoarthritis: pathogenic signaling pathways and therapeutic targets. Signal transduction and targeted therapy, 8(1), 56.
  32. Yoneda, M., Yamagata, M., Suzuki, S., & Kimata, K. (1988). Hyaluronic acid modulates proliferation of mouse dermal fibroblasts in culture. Journal of cell science, 90(2), 265-273.
  33. Alexander, L. A., Denisov, L. N., Zotkin, E. G., Dydykina, I. S., Kochish, A. Y., Rodionova, S. S.,. & Gallelli, L. (2021). Pharmacological management of osteoarthritis with a focus on symptomatic slow-acting drugs: Recommendations from leading Russian experts. JCR: Journal of Clinical Rheumatology, 27(8), e533-e539.
  34. Bannuru, R. R., Osani, M. C., Vaysbrot, E. E., Arden, N. K., Bennell, K., Bierma-Zeinstra, S. M. A.,. & McAlindon, T. E. (2019). OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis and cartilage, 27(11), 1578-1589.
  35. Conrozier, T., Raman, R., Diraçoglu, D., Montfort, J., Bard, H., Baron, D.,. & Henrotin, Y. (2024). EUROVISCO consensus guidelines for the use of hyaluronic acid viscosupplementation in knee osteoarthritis based on patient characteristics. Cartilage, 19476035241271970.
  36. De Tollenaere, M., Corriou, A., Durduret, A., Bernheim-Dennery, M., Haupt, T., Natsch, A.,. & Reynaud, R. (2025). In Vitro and Ex Vivo Investigations on the Tolerance and Safety of a 3 kDa Sodium Hyaluronate for Topical Application. Cosmetics, 12(6), 266.
  37. Kolasinski, S. L., Neogi, T., Hochberg, M. C., Oatis, C., Guyatt, G., Block, J.,. & Reston, J. (2020). 2019 American College of Rheumatology/Arthritis Foundation guideline for the management of osteoarthritis of the hand, hip, and knee. Arthritis & rheumatology, 72(2), 220-233.
  38. Kucharz, E. J., Szántó, S., Ivanova Goycheva, M., Petronijević, M., Šimnovec, K., Domżalski, M.,. & Reginster, J. Y. (2019). Endorsement by Central European experts of the revised ESCEO algorithm for the management of knee osteoarthritis. Rheumatology International, 39(7), 1117-1123.
  39. Soenen, S. J., Manshian, B., Montenegro, J. M., Amin, F., Meermann, B., Thiron, T.,. & Braeckmans, K. (2012). Cytotoxic effects of gold nanoparticles: a multiparametric study. ACS nano, 6(7), 5767-5783.
  40. Steinmetz, J. D., Culbreth, G. T., Haile, L. M., Rafferty, Q., Lo, J., Fukutaki, K. G.,. & Singh, S. (2023). Global, regional, and national burden of osteoarthritis, 1990–2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet Rheumatology, 5(9), e508-e522.
  41. Yao, Q., Wu, X., Tao, C., Gong, W., Chen, M., Qu, M.,. & Xiao, G. (2023). Osteoarthritis: pathogenic signaling pathways and therapeutic targets. Signal transduction and targeted therapy, 8(1), 56.