Eren POLAT, Ömer KAYGILI, Yesari ERÖKSÜZ, Mustafa KÖM, Okan ERKMEN

Hidroksiapatit Esaslı Biyoseramik Malzemelerin İn vitro ve İnvivo Biyouyumluluklarının Belirlenmesi

Büyük kemik defektleri kendiliğinden iyileşmesi mümkün olmayıp greftlenmesi gerekir. Bu çalışmada tarafımızdan üretilen hidroksiapatit (HAp) esaslı biyoseramik malzemelerin in vitro ve in vivo biyouyumlulukların belirlenmesi amaçlandı. İn vivo deneyleri için her grupta 7 hayvan olacak şekilde 3 gruba ayrılan 42 adet Spraque Dawleyratları kullanıldı. Ratların genel anestezi altında proksimal tibianın medial bölgesinde ikişer adet 2 mm’lik drille kemik defekti oluşturuldu. Oluşturulan defektlere 1. gruptaki olgulara kontrol grubu, 2. gruptaki olgulara ise tarafımızca üretilen alternatif HAp kemik greftleri ile dolduruldu. Üçüncü gruptaki olgulara da ticari hidroksapatit greftleri dolduruldu. Daha sonra operasyon bölgesi rutin cerrahi kurallara uygun olarak kapatıldı. Bütün ratlar postoperatif 14. ve 28. günlerde sakrifiye edildi. Histopatolojik değerlendirmelerde üretilen HAp impalantın kemikleşme sürecinde olduğu gözlendi. Sonuç olarak, üretilen HAp kemik grefti olarak kullanılabilirliği uzun süreli ve detaylı araştırmalar ileortaya konulması yararlı olacağı kanısına varıldı.

Determination of In vitro and In vivo Biocompability of Hydroxyapatite Based Bioceramic Materials

The reconstruction of large bone defects can not self-repair and needs bone grafts. It was aimed atinvestigating in vitro and in vivo biocompability of hydroxyapatite (HAp) based bioceramic materialsthat we produced. In this study, 42 Spraq dawley rats were used for in vivo study. Rats divided into 3 groups equally.After general anesthesia, rats were drilled 2 defect of 2 mm on the upper poximal metaphysis oftibia. In the first group bone defect were left to heal by themselves without using any material. Bonedefect were reconstructed with HAp material in the second group. Third group were filled withcommercial HAp. Operation wounds were closed using routine surgery. The rats were sacrificed atthe postoperative of $14^{th}$ or $28^{th}$ days. Histopathologicaly, It was observed that the HAp producedwas in the ossicification process. As a result, we need long term and more detailed examinations for evaluation of hydroxyapatitebased bioceramic materials.

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1. Can HN. Tavşanlarda Deneysel Olarak Oluşturulan Kemik Defektlerinin İyileşmesi Üzerinde Değişik Greft Materyalleri ve Trombositten Zengin Fibrin’in Etkilerinin İncelenmesi. Doktora Tezi, Elazığ: Fırat Üniversitesi, Sağlık Bilimleri Enstitüsü, 2013.
2. Durmuş AS, Çeribaşı AO, Can HN. Effects of coral and demineralized bone matrix on bone healing. FÜ Sağ Bil Vet Derg 2016; 30: 131-136.
3. Fırat Öztopalan D, Durmuş AS. Biyoaktif cam ile mineralize ve demineralize kemik matriksinin kemik iyileşmesi üzerindeki etkilerinin radyolojik olarak karşılaştırılması. FÜ Sağ Bil Vet Derg 2018; 32: 1-5.
4. Frost H. The biology of fracture healing. Part I. Clin Orthop Rel Res 1989; 248: 283-293.
5. Frost H. The biology of fracture healing. Part II. Clin Orthop Rel Res 1989; 248: 294-309.
6. Buckwalter JA, Glimcher MJ, Cooper RR, Recker R. Bone biology I: Structure, blood supply, cells, matrix and mineralization. Instructional Course Lectures 1996; 45: 371-386.
7. Junqueira L.C, Carneiro J. Basic Histology. 10th Baskı, New York: McGraw-Hill, 2003.
8. Kaygılı Ö. Sol Jel Metodu ile Üretilen Hidroksiapatit Esaslı Biyoseramik Malzemelerin Mikroyapı ve Fiziksel Özelliklerinin İncelenmesi. Doktora Tezi, Elazığ: Fırat Üniversitesi, Fen Bilimleri Enstitüsü, 2011.
9. Kayalı ES. Ticari İnert Cam Katkılı Hidroksiapatit-alümina ve Hidroksiapatit-zirkonya Kompozitlerinin Üretimi ve Karakterizasyonu. Yüksek Lisans Tezi, İstanbul: İstanbul Teknik Üniversitesi, Fen Bilimleri Enstitüsü, 2014.
10. Yuan H, Fernandes H, Habibovic P, et al. Osteoinductive ceramics as a synthetic alternative to autologous bone grafting. PNAS 2010; 107: 13614-13619.
11. Zhang JC, Lu HY, Lv GY, et al. The repair of critical-size defects with porous hydroxyapatite/polyamide nanocomposite: An experimental study in rabbit mandibles. Int J Oral Maxillofac Surg 2010; 39: 469-477.
12. Landi E, Tampieri A, Celotti G. Sprio, S. Densification behaviour and mechanisms of synthetic hydroxyapatites. J Eur Ceram Soc 2000; 20: 2377-2387.
13. Chang BS, Lee CK, Hong KS, et al. Osteoconduction at porous hydroxyapatite with various pore configurations. Biomaterials 2000; 21: 1291-1298.
14. Boo JS, Yamada Y, Okazaki Y, et al. Tissue-engineered bone using mesenchymal stem cells and a biodegradable scaffold. J Craniofacial Surg 2002; 13: 231-239.
15. Develioğlu H. Kritik boyutlu ve kritik boyutlu olmayan defektler. Cumhuriyet Üniversitesi Diş Hekimliği Fakültesi Dergisi 2003; 6: 60-63.
16. Liu FZ, Wang DW, Zhang YJ, et al. Comparison of rabbit rib defect regeneration with and without graft. J Mater Sci. Mater Med 2017; 28: 2-6.
17. Hollinger JO, Kleinschmidt JC. The critical size defect as an experimental model to test bone repair materials. J Craniofac Surg. 1990; 1: 60-68.
18. Mulliken JB, Glowacki J. Induced osteogenesis for repair and construction in the craniofacial region. Plast. Reconstr Surg 1980; 65: 553-560.
19. Glowacki J, Kaban LB, Murray JE, Folkman J, Mulliken JB. Application of the biological principle of induced osteogenesis for craniofacial defects. Lancet 1981; 2: 959-962.
20. El-Rashidy AA, Roether JA, Harhaus L, Kneser U, Boccaccini AR. Regenerating bone with bioactive glass scaffolds: A review of in vivo studies in bone defect models. Acta Biomater 2017; 62: 1-28.
21. Sergeeva NS, Sviridova IK, Frank GA, et al. Criteria of biocompatibility of materials for bone defect repair. Bull Exp Biol Med.2014;157: 689-694.
22. Cestari TM, Granjeiro JM, De Assis GF, Garlet GP, Taga R. Bone repair and augmentation using block of sintered bovine-derived anorganic bone graft in cranial bone defect model. Clin Oral Implants Res 2009; 340-350.
23. Alberius P, Johnell O. Repair of Membraneous Bone Fractures and Defects in Rats. J Cranio Maxillofacial Surg 1991; 19: 15-20.
24. Schmid J, Wallkamm B, Hammerle CH, Gogolewski S, Lang NP. The significance of angiogenesis in guided bone regeneration. A case report of a rabbit experiment. Clin Oral Implants Res 1997; 8: 244-248.
25. Herron S, Thordarson DB, Winet H, Luk A, Bao JY. Ingrowth of bone into absorbable bone cement: An in vivo microscopic evaluation. Am J Orthop 2003; 32: 581-584.
26. Huang YH, Jakus AE, Jordan SW, et al. Threedimensionally printed hyperelastic bone scaffolds accelerate bone regeneration in critical-size calvarial bone defects. Plast Reconstr. Surg 2019; 143: 1397-1407.
27. Lee JE, Bark CW, Quy HV, et al. Effects of Enhanced Hydrophilic Titanium Dioxide Coated Hydroxyapatite on Bone Regeneration in rabbit Calvarial Defects. Int J Mol Sci 2018; 19: 36-40
28. Hamidabadi HG, Shafaroudi MM, Seifi M, et al. Repair of critical-sized rat calvarial defects with three-dimensional hydroxyapatite-gelatin scaffolds and bone marrow stromal stem cells. Med Arch 2018; 72: 88-93.
29. Fillingham Y, Jacobs J. Bone gafts and their substitutes. Bone Joint J 2016; 98-B(1 Suppl A): 6-9.
30. Zhang JC, Lu HY, Lv GY, Mo AC, Yan YG, Huang C. The repair of critical-size defects with porous hydroxyapatite/polyamide nanocomposite: An experimental study in rabbit mandibles. Int J Oral Maxillofac Surg 2010; 39: 469-477.
31. Sanz M, Vignoletti F. Key aspects on the use of bone substitutes for bone regeneration of edentulous ridges. Dent Mater 2015; 31: 640-647.
32. Sanchez de Val JE, Calvo-Guirado JL, Delgado-Ruiz RA, et al. Physical properties, mechanical behavior, and electron microscopy study of a new α-tcp block graft with silicon in an animal model. J Biomed Mater Res A 2012; 100: 3446-3454.
33. Zheng H, Bai Y, Shih MS, et al. Effect of a β-TCP collagen composite bone substitute on healing of drilled bone voids in the distal femoral condyle of rabbits. J Biomed Mater Res B Appl Biomater 2014;102: 376-383.