Osteokondral Doku Mühendisliği,

Öz

Ortopedik cerrahide, osteokondral hasarların tedavisi hala tam olarak gerçekleştirilememektedir. Osteokondral hasarlar, aynı anda hem eklem kıkırdağı hem de subkondral kemikte hasarın görüldüğü durumları ifade etmektedir. Bu hasarların tedavisi için kıkırdak, kemik ve kıkırdak-kemik ara yüzeyinin fiziksel ve kimyasal özelliklerini göz önünde bulunduracak yaklaşımlara ihtiyaç duyulmaktadır. Osteokondral hasarların tedavisi için birçok cerrahi yöntemi geliştirilmiş olsa da bu yöntemler geçici bir iyileşme sağlar. Bu nedenle tedavi edici alternatif yöntemler üzerinde yoğun bir şekilde çalışılmaktadır. Bu noktada, osteokondral doku mühendisliği, biyomalzeme, hücreler ve çeşitli biyoaktif moleküllerin kullanımıyla, osteokondral hasarların tedavisi için ön plana çıkmaktadır. Bu derlemede, osteokondral doku mühendisliğinin temelleri, osteokondral dokunun yapısı, osteokondral hasarların tedavisinde kullanılan cerrahi yöntemler, bu alanda kullanılan biyomalzemeler ve tek/çok fazlı doku iskelesi tasarımları ve kullanımları, kullanılan büyüme faktörleri ve hücreler örnekleriyle anlatılmıştır.

Anahtar Kelimeler

• Osteokondral doku mühendisliği,çok fazlı doku iskelesi,büyüme faktörü,kondrosit,kök hücre

Osteochondral Tissue Engineering

Öz

Treatment of osteochondral defects can not be completely achieved in orthopaedic surgery. Osteochondral defects reflect damage to both the articular cartilage as well as the underside subchondral bone. The treatment strategies should take into consideration the physical and chemical properties of cartilage, bone and cartilage-bone interface. Although there are several surgical methods developed for the treatment of osteochondral defects, both of them have ensured temporary healing. Therefore, there have been intense efforts on alternative strategies for osteochondral regeneration. At this point, osteochondral tissue engineering have come to the forefront by using the combinations of biomaterials, cells and several bioactive molecules. In this review, fundamentals of osteochondral tissue engineering, osteochondral tissue structure and surgical treatment methods, the biomaterials used and design of single/multiphasic scaffolds, growth factors and cells are comprehensively presented with the current literature examples.

Anahtar Kelimeler

• Osteochondral tissue engineering,multiphasic scaffold,growth factor,chondrocyte,stem cell

Kaynakça

1. S.P.NukavarapuandD.L.Dorcemus,“Osteochondraltissueengineering:currentstrategiesandchallenges,”Biotechnology advances, vol. 31, no. 5, pp. 706–721, 2013.
2. B. Alberts, “Molecular biology of the cell: Reference edition. number v. 1 in molecular biology of the cell: Reference edition,” 2008.
3. K. Athanasiou, C. Zhu, X. Wang, and C. Agrawal, “Effects of aging and dietary restriction on the structural integrity of rat articular cartilage,” Annals of biomedical engineering, vol. 28, no. 2, pp. 143–149, 2000.
4. D. Eyre and J. Wu, “Collagen structure and cartilage matrix integrity.” The Journal of rheumatology. Supplement, vol. 43, pp. 82–85, 1995.
5. T. Aigner, E. Reichenberger, W. Bertling, T. Kirsch, H. Stöss, and K. Von der Mark, “Type x collagen expression in osteoarthritic and rheumatoid articular cartilage,” Virchows Archiv B, vol. 63, no. 1, p. 205, 1993.
6. P. J. Yang and J. S. Temenoff, “Engineering orthopedic tissue interfaces,” Tissue Engineering Part B: Reviews, vol. 15, no. 2, pp. 127–141, 2009.
7. L. Fuentes-Mera, A. Camacho, N. K. Moncada-Saucedo, and V. Peña-Martínez, “Current applications of mesenchymal stem cells for cartilage tissue engineering,” in Mesenchymal Stem Cells-Isolation, Characterization and Applications. InTech, 2017.
8. A. R. Poole, T. Kojima, T. Yasuda, F. Mwale, M. Kobayashi, and S. Laverty, “Composition and structure of articular cartilage: a template for tissue repair,” Clinical Orthopaedics and Related Research vol. 391, pp. S26–S33, 2001.

9. R. M. Schinagl, D. Gurskis, A. C. Chen, and R. L. Sah, “Depth-dependent confined compression modulus of full-thickness bovine articular cartilage,” Journal of Orthopaedic Research, vol. 15, no. 4, pp. 499–506, 1997.
10. P. Mente and J. Lewis, “Elastic modulus of calcified cartilage is an order of magnitude less than that of subchondral bone,” Journal of Orthopaedic Research, vol. 12, no. 5, pp. 637–647, 1994.
11. C. E. Kawcak, C. W. McIlwraith, R. Norrdin, R. Park, and S. James, “The role of subchondral bone in joint disease: a review,” Equine veterinary journal, vol. 33, no. 2, pp. 120–126, 2001.
12. R. R. Pool and D. M. Meagher, “Pathologic findings and pathogenesis of racetrack injuries,” Veterinary Clinics of North America: Equine Practice, vol. 6, no. 1, pp. 1–30, 1990.
13. E. L. Radin, R. B. Martin, D. B. Burr, B. Caterson, R. D. Boyd, and C. Goodwin, “Effects of mechanical loading on the tissues of the rabbit knee,” Journal of Orthopaedic Research, vol. 2, no. 3, pp. 221–234, 1984.
14. D. B. Burr, “Anatomy and physiology of the mineralized tissues: role in the pathogenesis of osteoarthrosis,” Osteoarthritis and cartilage, vol. 12, pp. 20–30, 2004.
15. K. Moisio, F. Eckstein, J. S. Chmiel, A. Guermazi, P. Prasad, O. Almagor, J. Song, D. Dunlop, M. Hudelmaier, A. Kothari et al., “Denuded subchondral bone and knee pain in persons with knee osteoarthritis,” Arthritis & Rheumatology, vol. 60, no. 12, pp. 3703–3710, 2009.
16. S.Redman,S.Oldfield,C.Archeret al.,“Currentstrategiesforarticularcartilagerepair,”Eur Cell Mater,vol.9,no.23-32, pp. 23–32, 2005.
17. H. Upmeier, B. Brüggenjürgen, A. Weiler, C. Flamme, H. Laprell, and S. Willich, “Follow-up costs up to 5 years after conventional treatments in patients with cartilage lesions of the knee,” Knee Surgery, Sports Traumatology, Arthroscopy, vol. 15, no. 3, pp. 249–257, 2007.
18. J. B. Moseley, K. O’malley, N. J. Petersen, T. J. Menke, B. A. Brody, D. H. Kuykendall, J. C. Hollingsworth, C. M. Ashton, andN.P.Wray,“Acontrolledtrialofarthroscopicsurgeryforosteoarthritisoftheknee,”NewEnglandJournalofMedicine, vol. 347, no. 2, pp. 81–88, 2002.
19. S.Caffey,E.McPherson,B.Moore,T.Hedman,andC.T.Vangsness,“Effectsofradiofrequencyenergyonhumanarticular cartilage: an analysis of 5 systems,” The American journal of sports medicine, vol. 33, no. 7, pp. 1035–1039, 2005.
20. J. R. Steadman, W. G. Rodkey, and J. J. Rodrigo, “Microfracture: surgical technique and rehabilitation to treat chondral defects,” Clinical Orthopaedics and Related Research vol. 391, pp. S362–S369, 2001.
21. F. T. Blevins, J. R. Steadman, J. J. Rodrigo, and J. Silliman, “Treatment of articular cartilage defects in athletes: an analysis of functional outcome and lesion appearance,” Orthopedics, vol. 21, no. 7, pp. 761–768, 1998.
22. J. D. Harris, R. H. Brophy, R. A. Siston, and D. C. Flanigan, “Treatment of chondral defects in the athlete’s knee,” Arthroscopy, vol. 26, no. 6, pp. 841–852, 2010.
23. J. R. Steadman, K. K. Briggs, J. J. Rodrigo, M. S. Kocher, T. J. Gill, and W. G. Rodkey, “Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up,” Arthroscopy, vol. 19, no. 5, pp. 477–484, 2003.
24. G. Spahn, E. Kahl, T. Mückley, G. O. Hofmann, and H. M. Klinger, “Arthroscopic knee chondroplasty using a bipolar radiofrequency-based device compared to mechanical shaver: results of a prospective, randomized, controlled study,” Knee Surgery, Sports Traumatology, Arthroscopy, vol. 16, no. 6, pp. 565–573, 2008.
25. L. Hangody and Z. Karpati, “New possibilities in the management of severe circumscribed cartilage damage in the knee,” Magyar traumatologia, ortopedia, kezsebeszet, plasztikai sebeszet, vol. 37, no. 3, pp. 237–243, 1994.
26. R. Haene, E. Qamirani, R. A. Story, E. Pinsker, and T. R. Daniels, “Intermediate outcomes of fresh talar osteochondral allografts for treatment of large osteochondral lesions of the talus,” JBJS, vol. 94, no. 12, pp. 1105–1110, 2012.
27. M. Brittberg, A. Lindahl, A. Nilsson, C. Ohlsson, O. Isaksson, and L. Peterson, “Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation,” New england journal of medicine, vol. 331, no. 14, pp. 889–895, 1994.
28. A. Gobbi, E. Kon, M. Berruto, R. Francisco, G. Filardo, and M. Marcacci, “Patellofemoral full-thickness chondral defects treated with hyalograft-c: a clinical, arthroscopic, and histologic review,” The American journal of sports medicine, vol. 34, no. 11, pp. 1763–1773, 2006.
29. E.Kon,P.Verdonk,V.Condello,M.Delcogliano,A.Dhollander,G.Filardo,E.Pignotti,andM.Marcacci,“Matrix-assisted autologous chondrocyte transplantation for the repair of cartilage defects of the knee: systematic clinical data review and study quality analysis,” The American journal of sports medicine, vol. 37, no. 1_suppl, pp. 156–166, 2009.
30. A. G. McNickle, M. T. Provencher, and B. J. Cole, “Overview of existing cartilage repair technology,” Sports medicine and arthroscopy review, vol. 16, no. 4, pp. 196–201, 2008.
31. J. E. Jeon, C. Vaquette, T. J. Klein, and D. W. Hutmacher, “Perspectives in multiphasic osteochondral tissue engineering,” The Anatomical Record, vol. 297, no. 1, pp. 26–35, 2014.
32. S.I.Jeong,E.K.Ko,J.Yum,C.H.Jung,Y.M.Lee,andH.Shin,“Nanofibrouspoly(lacticacid)/hydroxyapatitecomposite scaffolds for guided tissue regeneration,” Macromolecular bioscience, vol. 8, no. 4, pp. 328–338, 2008.
33. C. R. Chu, R. D. Coutts, M. Yoshioka, F. L. Harwood, A. Z. Monosov, and D. Amiel, “Articular cartilage repair using allogeneic perichondrocyteseeded biodegradable porous polylactic acid (pla): A tissue-engineering study,” Journal of Biomedical Materials Research Part A, vol. 29, no. 9, pp. 1147–1154, 1995.
34. G.-I.ImandJ.H.Lee,“Repairofosteochondraldefectswithadiposestemcellsandadualgrowthfactor-releasingscaffold in rabbits,” Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol. 92, no. 2, pp. 552–560, 2010.
35. N.T.Khanarian,N.M.Haney,R.A.Burga,andH.H.Lu,“Afunctionalagarose-hydroxyapatitescaffoldforosteochondral interface regeneration,” Biomaterials, vol. 33, no. 21, pp. 5247–5258, 2012.
36. J. Malda, T. Woodfield, F. Van Der Vloodt, C. Wilson, D. Martens, J. Tramper, C. Van Blitterswijk, and J. Riesle, “The effect of pegt/pbt scaffold architecture on the composition of tissue engineered cartilage,” Biomaterials, vol. 26, no. 1, pp. 63–72, 2005.
37. J. M. Coburn, M. Gibson, S. Monagle, Z. Patterson, and J. H. Elisseeff, “Bioinspired nanofibers support chondrogenesis for articular cartilage repair,” Proceedings of the National Academy of Sciences, vol. 109, no. 25, pp. 10012–10017, 2012.
38. J. Zhou, C. Xu, G. Wu, X. Cao, L. Zhang, Z. Zhai, Z. Zheng, X. Chen, and Y. Wang, “In vitro generation of osteochondral differentiation of human marrow mesenchymal stem cells in novel collagen–hydroxyapatite layered scaffolds,” Acta Biomaterialia, vol. 7, no. 11, pp. 3999–4006, 2011.
39. J. Jiang, A. Tang, G. A. Ateshian, X. E. Guo, C. T. Hung, and H. H. Lu, “Bioactive stratified polymer ceramic-hydrogel scaffold for integrative osteochondral repair,” Annals of biomedical engineering, vol. 38, no. 6, pp. 2183–2196, 2010.
40. G. Chen, T. Sato, J. Tanaka, and T. Tateishi, “Preparation of a biphasic scaffold for osteochondral tissue engineering,” Materials Science and Engineering: C, vol. 26, no. 1, pp. 118–123, 2006.
41. T. Deng, J. Lv, J. Pang, B. Liu, and J. Ke, “Construction of tissue-engineered osteochondral composites and repair of large joint defects in rabbit,” Journal of tissue engineering and regenerative medicine, vol. 8, no. 7, pp. 546–556, 2014.
42. Z. Cao, S. Hou, D. Sun, X. Wang, and J. Tang, “Osteochondral regeneration by a bilayered construct in a cell-free or cell-based approach,” Biotechnology letters, vol. 34, no. 6, pp. 1151–1157, 2012.
43. S.Çakmak,A.S.Çakmak,D.L.Kaplan,and M.Gümüs¸derelioglu,“Asilkfibroinandpeptideamphiphile-basedco-culture model for osteochondral tissue engineering,” Macromolecular bioscience, vol. 16, no. 8, pp. 1212–1226, 2016.
44. K. Ye, C. Di Bella, D. E. Myers, and P. F. Choong, “The osteochondral dilemma: review of current management and future trends,” ANZ journal of surgery, vol. 84, no. 4, pp. 211–217, 2014.
45. P. Angele, R. Kujat, M. Nerlich, J. Yoo, V. Goldberg, and B. Johnstone, “Engineering of osteochondral tissue with bone marrow mesenchymal progenitor cells in a derivatized hyaluronan-gelatin composite sponge,” Tissue Engineering, vol. 5, no. 6, pp. 545–553, 1999.
46. X.Wang,E.Wenk,X.Zhang,L.Meinel,G.Vunjak-Novakovic,andD.L.Kaplan,“Growthfactorgradientsviamicrosphere delivery in biopolymer scaffolds for osteochondral tissue engineering,” Journal of Controlled Release, vol. 134, no. 2, pp. 81–90, 2009.
47. D.M.Yunos,Z.Ahmad,V.Salih,andA.Boccaccini,“Stratifiedscaffoldsforosteochondraltissueengineeringapplications: electrospun pdlla nanofibre coated bioglass -derived foams,” Journal of biomaterials applications, vol. 27, no. 5, pp.537–551, 2013.
48. R. Mauck, X. Yuan, and R. Tuan, “Chondrogenic differentiation and functional maturation of bovine mesenchymal stem cells in long-term agarose culture,” Osteoarthritis and cartilage, vol. 14, no. 2, pp. 179–189, 2006.
49. T. Vinardell, S. Thorpe, C. Buckley, and D. Kelly, “Chondrogenesis and integration of mesenchymal stem cells within an in vitro cartilage defect repair model,” Annals of biomedical engineering, vol. 37, no. 12, p. 2556, 2009.
50. Y. Asawa, T. Ogasawara, T. Takahashi, H. Yamaoka, S. Nishizawa, K. Matsudaira, Y. Mori, T. Takato, and K. Hoshi, “Aptitude of auricular and nasoseptal chondrocytes cultured under a monolayer or three-dimensional condition for cartilage tissue engineering,” Tissue Engineering Part A, vol. 15, no. 5, pp. 1109–1118, 2008.
51. E. M. Darling and K. A. Athanasiou, “Rapid phenotypic changes in passaged articular chondrocyte subpopulations,” Journal of Orthopaedic Research, vol. 23, no. 2, pp. 425–432, 2005.
52. K. Yonenaga, S. Nishizawa, Y. Fujihara, Y. Asawa, K. Sanshiro, S. Nagata, T. Takato, and K. Hoshi, “The optimal conditions of chondrocyte isolation and its seeding in the preparation for cartilage tissue engineering,” Tissue Engineering Part C: Methods, vol. 16, no. 6, pp. 1461–1469, 2010.
53. E. J. Sheehy, C. T. Buckley, and D. J. Kelly, “Chondrocytes and bone marrow-derived mesenchymal stem cells undergoing chondrogenesis in agarose hydrogels of solid and channelled architectures respond differentially to dynamic culture conditions,” Journal of tissue engineering and regenerative medicine, vol. 5, no. 9, pp. 747–758, 2011.
54. L. M. Ball, M. E. Bernardo, H. Roelofs, A. Lankester, A. Cometa, R. M. Egeler, F. Locatelli, and W. E. Fibbe, “Cotransplantation of ex vivo–expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem-cell transplantation,” Blood, vol. 110, no. 7, pp. 2764–2767, 2007.
55. C. Csaki, P. Schneider, and M. Shakibaei, “Mesenchymal stem cells as a potential pool for cartilage tissue engineering,” Annals of Anatomy-Anatomischer Anzeiger, vol. 190, no. 5, pp. 395–412, 2008.
56. B. Johnstone, T. M. Hering, A. I. Caplan, V. M. Goldberg, and J. U. Yoo, “In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells,” Experimental cell research, vol. 238, no. 1, pp. 265–272, 1998.
57. G. Shen, “The role of type x collagen in facilitating and regulating endochondral ossification of articular cartilage,” Orthodontics & craniofacial research, vol. 8, no. 1, pp. 11–17, 2005