Semih AYANOĞLU, CEM ZEKİ ESENYEL, Oktay ADANIR, Semih DEDEOĞLU, Yunus İMREN, Tuğçe ESEN

Effects of hyaluronic acid (Hyalonect) on callus formation in rabbits ( EXPERIMENTAL STUDY)

Objective: Bone fragment and graft stabilization are important during reconstructive surgery of cases with comminuted fractures and bone defects. We examined the effect of Hyalonect surgical mesh on the healing dynamics of metaphyseal bone defects created in rabbit tibiae. Methods: Approximately 5-mm defects were created on the anterior aspect of the proximal tibial metaphysis of 80 male rabbits. The rabbits were randomly assigned to four groups: Group I, bone defects left alone (control group); Group II, bone defect covered with Hyalonect; Group III, bone defect filled with allograft; and Group IV, bone defect filled with allograft and covered with Hyalonect. Results: No significant histological differences were noted between Groups II and III or Groups III and IV at 3 and 6 weeks. At 3 weeks, Groups II, III, and IV had significantly better healing than Group I (p<0.05). In addition, Group IV showed significantly better healing than Group II at 3 and 6 weeks. At 6 weeks, only Group IV showed better healing than Group I (p<0.05). Radiologically, Groups II, III, and IV showed better healing than Group I at 3 and 6 weeks (p<0.05). Conclusion: Hyalonect application and bone grafting significantly accelerated the healing process when used alone or together. Hyalonect application along with bone grafting resulted in better early radiological healing than bone grafting alone.

___

1. Rhodes NP, Hunt JA, Longinotti C, Pavesio A. In vivo characterization of Hyalonect, a novel biodegradable surgical mesh. J Surg Res 2011;168:318.

2. Aslan M, Simsek G, Dayi E. The effect of hyaluronic acidsupplemented bone graft in bone healing: experimental study in rabbits. J Biomater Appl 2006;20:20920.

3. Fröhlich M, Grayson WL, Wan LQ, Marolt D, Drobnic M, Vunjak-Novakovic G. Tissue engineered bone grafts: biological requirements, tissue culture and clinical relevance. Curr Stem Cell Res Ther 2008;3:25464.

4. Mizuno M, Shindo M, Kobayashi D, Tsuruga E, Amemiya A, Kuboki Y. Osteogenesis by bone marrow stromal cells maintained on type I collagen matrix gels in vivo. Bone 1997;20:1017.

5. Grundel RE, Chapman MW, Yee T, Moore DC. Autogeneic bone marrow and porous biphasic calcium phosphate ceramic for segmental bone defects in the canine ulna. Clin Orthop Relat Res 1991;266:24458.

6. Stevens MM. Biomaterials for bone tissue engineering. Materials today 2008;11:1825.

7. Schwartzmann M. Use of collagen membranes for guided bone regeneration: a review. Implant Dent 2000;9:636.

8. Pirnazar P, Wolinsky L, Nachnani S, Haake S, Pilloni A, Bernard GW. Bacteriostatic effects of hyaluronic acid. J Periodontol 1999;70:3704.

9. Kennedy CI, Diegelmann RF, Haynes JH, Yager DR. Proinflammatory cytokines differentially regulate hyaluronan synthase isoforms in fetal and adult fibroblasts. J Pediatr Surg 2000;35:8749.

10. Nandi A, Estess P, Siegelman MH. Hyaluronan anchoring and regulation on the surface of vascular endothelial cells is mediated through the functionally active form of CD44. J Biol Chem 2000;275:1493948.

11. Watanabe H, Cheung SC, Itano N, Kimata K, Yamada Y. Identification of hyaluronan-binding domains of aggrecan. J Biol Chem 1997;272:2805765.

12. Pilloni A, Bernard GW. The effect of hyaluronan on mouse intramembranous osteogenesis in vitro. Cell Tissue Res 1998;294:32333.

13. West DC, Hampson IN, Arnold F, Kumar S. Angiogenesis induced by degradation products of hyaluronic acid. Science 1985;228:13246.

14. Wight TN, Kinsella MG, Qwarnström EE. The role of proteoglycans in cell adhesion, migration and proliferation. Curr Opin Cell Biol 1992;4:793801.

15. Fraser JR, Laurent TC, Laurent UB. Hyaluronan: its nature, distribution, functions and turnover. J Intern Med 1997;242:2733.

16. Toole BP. Hyaluronate and hyaluronidase in morphogenesis and differentiation. Amer Zool 1973;13:10615.

17. Handley CJ, Lowther DA. Inhibition of proteoglycan biosynthesis by hyaluronic acid in chondrocytes in cell culture. Biochim Biophys Acta 1976;444:6974.

18. Boyce DE, Thomas A, Hart J, Moore K, Harding K. Hyaluronic acid induces tumour necrosis factor-alpha production by human macrophages in vitro. Br J Plast Surg 1997;50:3628.

19. Sasaki T, Watanabe C. Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid. Bone 1995;16:915.

20. Stern M, Schmidt B, Dodson TB, Stern R, Kaban LB. Fetal cleft lip repair in rabbits: histology and role of hyaluronic acid. J Oral Maxillofac Surg 1992;50:2639

21. Emery SE, Brazinski MS, Koka A, Bensusan JS, Stevenson S. The biological and biomechanical effects of irradiation on anterior spinal bone grafts in a canine model. J Bone Joint Surg Am 1994;76:5408.

22. Yasko AW, Lane JM, Fellinger EJ, Rosen V, Wozney JM, Wang EA. The healing of segmental bone defects, induced by recombinant human bone morphogenetic protein (rhBMP-2). A radiographic, histological, and biomechanical study in rats. J Bone Joint Surg Am 1992;74:65970.

23. Oakes DA, Lee CC, Lieberman JR. An evaluation of human demineralized bone matrices in a rat femoral defect model. Clin Orthop Relat Res 2003;413:28190.

24. Maus U, Andereya S, Gravius S, Siebert CH, Ohnsorge JA, Niedhart C. Lack of effect on bone healing of injectable BMP-2 augmented hyaluronic acid. Arch Orthop Trauma Surg 2008;128:14616.

25. Hunt DR, Jovanovic SA, Wikesjö UM, Wozney JM, Bernard GW. Hyaluronan supports recombinant human bone morphogenetic protein-2 induced bone reconstruction of advanced alveolar ridge defects in dogs. A pilot study. J Periodontol 2001;72:6518.

26. Kim HD, Valentini RF. Retention and activity of BMP-2 in hyaluronic acid-based scaffolds in vitro. J Biomed Mater Res 2002;59:57384.

27. Solchaga LA, Dennis JE, Goldberg VM, Caplan AI. Hyaluronic acid-based polymers as cell carriers for tissueengineered repair of bone and cartilage. J Orthop Res 1999;17:20513.

28. Gauthier O, Bouler JM, Aguado E, Pilet P, Daculsi G. Macroporous biphasic calcium phosphate ceramics: influence of macropore diameter and macroporosity percentage on bone ingrowth. Biomaterials 1998;19:1339.

29. Sasaki T, Watanabe C. Stimulation of osteoinduction in bone wound healing by high-molecular hyaluronic acid. Bone 1995;16:915.

30. Campoccia D, Doherty P, Radice M, Brun P, Abatangelo G, Williams DF. Semisynthetic resorbable materials from hyaluronan esterification. Biomaterials 1998;19:2101 27.

31. Schmitz JP, Hollinger JO. The critical size defect as an experimental model for craniomandibulofacial nonunions. Clin Orthop Relat Res 1986;205:299&308.

32. de Brito Bezerra B, Mendes Brazão MA, de Campos ML, Casati MZ, Sallum EA, Sallum AW. Association of hyaluronic acid with a collagen scaffold may improve bone healing in critical-size bone defects. Clin Oral Implants Res 2012;23:93842.

33. Najjar TA, Kahn D. Comparative study of healing and remodeling in various bones. J Oral Surg 1977;35:3759.

34. Aaboe M, Pinholt EM, Hjørting-Hansen E. Healing of experimentally created defects: a review. Br J Oral Maxillofac Surg 1995;33:3128.

35. Kilborn SH, Trudel G, Uhthoff H. Review of growth plate closure compared with age at sexual maturity and lifespan in laboratory animals. Contemp Top Lab Anim Sci 2002;41:216.