İNSAN AMNİYOTİK SIVISI VE MEMBRANININ BİR TAVŞAN DİZİ KIKIRDAK DEFEKTİ MODELİNDE KONDRAL İYİLEŞME ÜZERİNE ETKİLERİ

Öz

Amaç Artiküler kıkırdağın kısıtlı intrensek iyileşmesi ve tamir kapasitesinin az olması nedeniyle çoğu tedavi metodları ile normal hyalen kıkırdak rejenerasyonu sağlanamamakta ve sonuç olarak osteoartroz gelişebilmektedir. Bu çalışmada insan amniyotik sıvısı ve membranının tavşanlardaki kondral defektlerdeki etkilerini incelemek amaçlanmıştır. Gereç ve Yöntem 32 immatür albino Yeni Zelanda tavşanının 64 dizi bu çalışmaya dahil edildi. Tam kat kıkırdak defektleri tavşanların medial kondillerinin yük taşıma yüzeylerinde cerrahi olarak oluşturuldu. Tavşanlar randomize olarak dört gruba bölündü: ek tedavi verilmeyenler Grup 1, 0,3 ml insan amniyotik sıvısı (İAS) verilenler Grup 2, sadece insan amniyotik membranı (İAM) verilenler Grup 3, hem 0,3 ml İAS hem İAM verilenler Grup 4’ü oluşturdu. Kondiller histopatolojik olarak 4. ve 12. haftalarda modifiye O’Driscoll evreleme skalası ile değerlendirildi. Sonuçlar Mann-Whitney U ve ANOVA testleri ile istatistiksel olarak analiz edildi. Bulgular Gruplar arasında rejenere dokunun kalitesi açısından istatistiksel olarak anlamlı fark bulunmadı (p>0.05). Grupların ortalama sonuçları 12. haftada, 4. hafta sonuçlarından daha kötü olarak saptandı; buna rağmen bu farkın, sadece Grup 1 (sham grubu) ve Grup 4 açısından anlamlı olduğu görüldü (İAS+İAM) (sırasıyla, p=0,007 ve p=0,014). Sonuç Sadece İAS, sadece İAM ve her iki biyomateryalin kombine edildiği tedavi yöntemlerinin hiçbirinde kıkırdak defekt iyileşmesi daha iyi ve kaliteli olmadığı ve birbirlerine de bir üstünlüğü olmadığı görüldü. Bu çalışmada gösterilmiş olan 4. hafta sonuçlarının 12. hafta sonuçlarından daha iyi olmasının çalışmada kullanılan immatür tavşanlardaki intrensek tamir mekanizmasındaki erken rejenerasyon kapasitesinden kaynaklandığını düşünmekteyiz.

Anahtar Kelimeler

• hyalen kıkırdak
• kıkırdak rejenerasyonu
• kondral defekt
• insan amniyotik sıvısı
• insan amniyotik membranı

THE EFFECTS OF HUMAN AMNIOTIC FLUID AND MEMBRANE ON CHONDRAL HEALING IN A RABBIT KNEE CARTILAGE DEFECT MODEL

Öz

Objective Due to the limited intrinsic healing and repair capacity of the articular cartilage, most treatment methods cannot achieve reliable regeneration of normal hyaline cartilage, resulting in early development of osteoarthritis. The purpose of this study was to determine the effects of human amniotic fluid and membrane on chondral defects. Material and Methods Sixty-four knees of 32 immature New Zealand rabbits were included in the study. Full thickness chondral defects were created in the weight-bearing surface of the medial condyles of the rabbits. The rabbits were divided randomly into four groups: no adjunct treatment was given in group 1, 0.3 ml human amniotic fluid (HAF) alone in group 2, human amniotic membrane (HAM) alone in group 3 and both of 0.3 ml HAF and HAM in group 4 was administered. The condyles were histopathologically evaluated at 4th and 12th week using the modified O’Driscoll Grading Scale. Results There were no significant differences in the quality of the regenerated tissue within and between groups (p>0.05). The mean results of groups at the 12th week were worse than results at the 4th week; however, the difference was statistically significant for only the sham group (group 1) and the combined therapy group (group 4) (p=0.007 and p=0.014, respectively). Conclusion HAF alone, HAM alone, and combined administration of both biomaterials neither affected chondral defect healing nor had any differences between each other. Nevertheless, we believe that some early regeneration due to an intrinsic repair mechanism is possible in immature rabbits as this study showed better results at 4th week than those at 12th week, although they are prone to degenerative processes in long-term follow-up. We suggest that a larger sample size in an experimental study would probably display a statistically significant difference when investigating effects of HAF, HAM, or both.

Anahtar Kelimeler

• hyaline cartilage
• cartilage regeneration
• chondral defect
• human amniotic fluid
• human amniotic membrane

Kaynakça

1. 1. Steadman JR, Briggs KK, Rodrigo JJ, Kocher MS, Gill TJ, Rodkey WG. Outcomes of microfracture for traumatic chondral defects of the knee: Average 11-year follow-up. Arthrosc J Arthrosc Relat Surg 2003 May;19(5):477–84.
2. 2. Brandt KD, Block JA, Michalski JP, Moreland LW, Caldwell JR, Lavin PT. Efficacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis. ORTHOVISC Study Group. Clin Orthop Relat Res. 2001 Apr;(385):130–43.
3. 3. Leighton R, Fitzpatrick J, Smith H, Crandall D, Flannery CR, Conrozier T. Systematic clinical evidence review of NASHA (Durolane hyaluronic acid) for the treatment of knee osteoarth- ritis. Open Access Rheumatol Res Rev. 2018 May;10:43–54.
4. 4. Dahl LB, Kimpton WG, Cahill RNP, Brown TJ, Fraser RE. The origin and fate of hyaluronan in amniotic fluid. J Dev Physiol. 1989 Oct;12(4):209–18.
5. 5. Longaker MT, Adzick NS, Hall JL, Stair SE, Crombleholme TM, Duncan BW, Bradley SM, Harrison MR, Stern R. Studies in fetal wound healing, VII. Fetal wound healing may be modulated by hyaluronic acid stimulating activity in amniotic fluid. J Pediatr Surg. 1990 Apr;25(4):430–3.
6. 6. Longaker MT, Scott Adzick N. The biology of fetal wound healing: A review. Plast Reconstr Surg. 1991 Apr;87(4):788–98.
7. 7. Gruss JS, Jirsch DW. Human amniotic membrane: A versatile wound dressing. Can Med Assoc J. 1978 May 20;118(10):1237- 46
8. 8. Tabet SK, Conner DM, Guebert DA. The Use of Human Amniotic Membrane for Cartilage Repair: A Sheep Study. Stem Cell Discov. 2015;05(04):40–7.

9. 9. Willett NJ, Thote T, Lin AS, Moran S, Raji Y, Sridaran S, Stevens HY, Guldberg RE. Intra-articular injection of micronized dehydrated human amnion/chorion membrane attenuates osteoarthritis development. Arthritis Res Ther. 2014;16(1):R47.
10. 10. Özgenel GY, Filiz G. Effects of human amniotic fluid on peripheral nerve scarring and regeneration in rats. J Neurosurg. 2003 Feb;98(2):371–7.
11. 11. Özgenel GY, Şamli B, Özcan M. Effects of human amniotic fluid on peritendinous adhesion formation and tendon healing after flexor tendon surgery in rabbits. J Hand Surg Am. 2001 Mar;26(2):332–9.
12. 12. Özgenel GY, Filiz G. Combined Application of Human Amniotic Membrane Wrapping and Hyaluronic Acid Injection in Epineurectomized Rat Sciatic Nerve. J Reconstr Microsurg. 2004 Mar;20(2):153–7.
13. 13. Grigolo B, Roseti L, Fiorini M, Fini M, Giavaresi G, Aldini NN, Giardino R, Facchini A. Transplantation of chondrocytes seeded on a hyaluronan derivative (Hyaff®-11) into cartilage defects in rabbits. Biomaterials. 2001 Sep;22(17):2417–24.
14. 14. Norris S., Pettifor J., Gray D., Buffenstein R. Calcium metabolism and bone mass in female rabbits during skeletal maturation: effects of dietary calcium intake. Bone. 2001 Jul;29(1):62–9.
15. 15. Karaçal N, Koşucu P, Çobanoğlu Ü, Kutlu N. Effect of human amniotic fluid on bone healing. J Surg Res. 2005;
16. 16. Wei X, Gao J, Messner K. Maturation-dependent repair of untreated osteochondral defects in the rabbit knee joint. J Biomed Mater Res. 1997 Jan;34(1):63–72.
17. 17. Solchaga LA, Yoo JU, Lundberg M, Dennis JE, Huibregtse BA, Goldberg VM, Caplan AI. Hyaluronan-based polymers in the treatment of osteochondral defects. J Orthop Res. 2000 Sep;18(5):773–80.
18. 18. Tuncel M, Halici M, Canoz O, Yildirim Turk C, Oner M, Ozturk F, Kabak S. Role of insulin like growth factor-I in repair response in immature cartilage. Knee. 2005 Apr;12(2):113–9.
19. 19. O'Driscoll SW, Fitzsimmons JS. The Role of Periosteum in Cartilage Repair. Clin Orthop Relat Res. 2001 Oct;391(391 SUPPL.):S190–207.
20. 20. Elmalı N, Kaygusuz MA, Ozen S, Baysal O, Inan M, Karakaplan M, Şarlak O. The healing effect of intraarticular hyaluronic acid injection on osteoarthritic knee: a study on rabbit knees. Acta Orthop Traumatol Turc. 1999; 33: 211-215
21. 21. Adams ME. An analysis of clinical studies of the use of crosslinked hyaluronan, hylan, in the treatment of osteoarthritis. J Rheumatol Suppl. 1993 Aug;39:16-8.
22. 22. Wobig M, Bach G, Beks P, Dickhut A, Runzheimer J, Schwieger G, Vetter G, Balazs E. The role of elastoviscosity in the efficacy of viscosupplementation for osteoarthritis of the knee: A comparison of Hylan G-F 20 and a lower-molecular-weight hyaluronan. Clin Ther 1999 Sep;21(9):1549–62.
23. 23. Fortier LA, Mohammed HO, Lust G, Nixon AJ. Insulin-like growth factor-I enhances cell-based repair of articular cartilage. J Bone Joint Surg Br. 2002 Mar;84(2):276-88.
24. 24. Vines J, Aliprantis A, Gomoll A, Farr J. Cryopreserved Amniotic Suspension for the Treatment of Knee Osteoarthritis. J Knee Surg. 2015 Dec 18;29(06):443–50.
25. 25. Kavakli K, Gurkok S, Caylak H, Genc O, Gamsizkan M, Yucel O, Karasahin E, Gozubuyuk A, Tasci C. Effects of human amniotic fluid on costal cartilage regeneration (an experimental study). Thorac Cardiovasc Surg. 2011 Dec;59(8):484-9.
26. 26. You Q, Liu Z, Zhang J, Shen M, Li Y, Jin Y, Liu Y. Human Amniotic Mesenchymal Stem Cell Sheets Encapsulating Cartilage Particles Facilitate Repair of Rabbit Osteochondral Defects. Am J Sports Med. 2020 Mar 15;48(3):599–611.
27. 27. Ghanmi S, Trigui M, Baya W, Ellouz Z, Elfeki A, Charfi S, Fricain JC, Keskes H. The periosteum-like effect of fresh human amniotic membrane on bone regeneration in a rabbit critical-sized defect model. Bone. 2018 May;110:392-404.
28. 28. Cheng ZJ, So RP, Byung HC, Lee KY, Choong KK, Min BH. Human amniotic membrane as a delivery matrix for articular cartilage repair. Tissue Eng. 2007 Apr;13(4):693-702.
29. 29. Zhang Z, Zeng L, Yang J, Guo L, Hou Q, Zhu F. Amniotic membrane-derived stem cells help repair osteochondral defect in a weight-bearing area in rabbits. Exp Ther Med. 2017 Jul;14(1):187–92.
30. 30. Pipino C, Pierdomenico L, Di Tomo P, Di Giuseppe F, Cianci E, D’Alimonte I, Morabito C, Centurione L, Antonucci I, Mariggiò MA, Di Pietro R, Ciccarelli R, Marchisio M, Romano M, Angelucci S, Pandolfi A. Molecular and phenotypic characterization of human amniotic fluid-derived cells: A morphological and proteomic approach. Stem Cells Dev. 2015 Jun 15;24(12):1415– 28.