Iranian Journal of Orthopedic Surgery

The Effect of Simultaneous Application of Blood Clot and Doxycycline on Bone Healing in Rabbit

Document Type : Original Article

Authors

Amin Bigham-Sadegh 1
Saeid Lotfi 2
Amad Oryan 3
Iman Hafar 2

1 Orthopedic Surgeon, Orthopaedic Surgeon, Department of Veterinary Surgery and Radiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.

2 Graduated DVM, Department of Veterinary Surgery and Radiology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.

3 Comparative Pathologist, Department of Veterinary Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.

https://doi.org/10.22034/ijos.2022.330332.1019
Abstract
Background: Facilitating the fracture healing process is important to increase the fracture healing speed and to decrease the time period till union. This study aimed to evaluate the effects of blood clot and doxycycline on bone healing process.
Methods: Twenty mature male New Zealand white rabbits were used, in this study. A defect was created in the middle part of the radius. The rabbits were randomly distributed into 4 groups and the gaps were filled with the graft materials: blood clot, doxycycline, combination of blood clot and doxycycline and control group in which the defect was left empty. Radiographs of operated limbs were taken on 14th, 28th, 42nd and 56th postoperative days. Histologic samples were taken on the 56th day post surgery.
Results: On radiographic evaluation significant difference between the groups was not observed (p>0.05). On histopathological evaluation, blood clot and doxycycline groups were superior to control group (P<0.05), also combination of blood clot and doxycycline group was superior to other ones (P<0.05). There was no evidence of graft rejection in any group.
Conclusion: This study demonstrated that the combination of blood clot and doxycycline has a better function in bone healing process than other groups.

Keywords

Biomaterial
Blood clot
Doxycycline
Bone regeneration
Rabbit
1.                   Osteocyte differentiation in the tibia of newborn rabbit: an ultrastructural study of the formation of cytoplasmic processes. Acta Anat. 1990; 137(4):350-8. PMID: 2368590 DOI: 10.1159/000146907.
2.                   Bigham-Sadegh A, Shadkhast M, Khalegi MR.Demineralized calf foetal growth plate effects on experimental bone healing in rabbit model. Veterinarski arhiv. 2013; 83(5):525-36.
3.                   Hafar I, Bigham-sadegh A, Nematollahi A, Karimi I, Lotfi S. The Effect of Fish Bone Powder and Human Lyophilized Platelet on Bone Healing in Rabbit Model. Iranian Journal of Orthopaedic Surgery. 2019; 17(2):57-69.
4.                   Finkemeier CG. Bone-Grafting and Bone-Graft Substitutes. J Bone Joint Surg Am. 2002; 84(3):454-64. PMID: 11886919 DOI: 10.2106/00004623-200203000-00020.
5.                   Bigham A, Dehghani S, Shafiei Z, Torabi Nezhad S.  Experimental bone defect healing with xenogenic demineralized bone matrix and bovine fetal growth plate as a new xenograft: radiological, histopathological and biomechanical evaluation. Cell Tissue Bank. 2009; 10(1):33-41. PMID: 18810656 DOI: 10.1007/s10561-008-9107-y.
6.                   Trotter JF. Transmission of hepatitis C by implantation of a processed bone graft: a case report. J Bone Joint Surg Am. 2003; 85(11):2215-7. PMID: 14630857 DOI: 10.2106/00004623-200311000-00026.
7.                   Ng VY. Risk of disease transmission with bone allograft. Orthopedics. 2012; 35(8):679-81. PMID: 22868589 DOI: 10.3928/01477447-20120725-04.
8.                   Burton EC. Burns DK. Opatowsky MJ. El-Feky WH. Fischbach B. et al. Rabies encephalomyelitis: clinical, neuroradiological, and pathological findings in 4 transplant recipients. Arch Neurol. 2005; 62(6):873-82. PMID: 15956158 DOI: 10.1001/archneur.62.6.873.
9.                   Laurencin CT, Jiang T. Bone Graft Substitutes and Bone Regenerative Engineering: ASTM International; 2014.
10.                Bezerra M, Brito G, Ribeiro R, Rocha F. Low-dose doxycycline prevents inflammatory bone resorption in rats. Braz J Med Biol Res. 2002; 35(5):613-6. PMID: 12011948 DOI: 10.1590/s0100-879x2002000500015.
11.                Hanemaaijer R, Visser H, Koolwijk P, Sorsa T, Salo T. et al. Inhibition of MMP synthesis by doxycycline and chemically modified tetracyclines (CMTs) in human endothelial cells. Adv Dent Res. 1998; 12(2):114-8. PMID: 9972133 DOI: 10.1177/08959374980120010301.
12.                Zhang C, TANG TT, REN WP, ZHANG Xl, DAI KR.  Inhibiting wear particles‐induced osteolysis with doxycycline. Acta Pharmacol Sin. 2007; 28(10):1603-10. PMID: 17883947 DOI: 10.1111/j.1745-7254.2007.00638.x.
13.                                Gomes PS, Fernandes MH. Effect of therapeutic levels of doxycycline and minocycline in the proliferation and differentiation of human bone marrow osteoblastic cells. Arch Oral Biol. 2007; 52(3):251-9. PMID: 17141175 DOI: 10.1016/j.archoralbio.2006.10.005.
14.                                Bedi A, Fox A, Kovacevic D, Deng XH, Warren R. et al.Doxycycline-Mediated Inhibition of Matrix Metalloproteinases Improves Healing After Rotator Cuff Repair. Am J Sports Med. 2010; 38(2):308-17. PMID: 19826139 DOI: 10.1177/0363546509347366.
15.                                do Nascimento Gomes K, Alves APNN, Dutra PGP, de Barros Viana GS.  Doxycycline induces bone repair and changes in Wnt signalling. Int J Oral Sci. 2017; 9(3):158-66. PMID: 28960195 PMCID: PMC5709545 DOI: 10.1038/ijos.2017.28.
16.                                Slatter DH. Textbook of small animal surgery: Elsevier Health Sciences; rd Edition (2-Volume Set). 2003.
17.                                Wang X, Friis T, Glatt V, Crawford R, Xiao Y. Structural properties of fracture haematoma: current status and future clinical implications. J Tissue Eng Regen Med. 2017; 11(10):2864-75. PMID: 27401283 DOI: 10.1002/term.2190.
18.                                Preininger B, Gerigk H, Bruckner J, Perka C, Schell H, et al. An experimental setup to evaluate innovative therapy options for the enhancement of bone healing using BMP as a benchmark–a pilot study. Eur Cell Mater. 2012; 23:262-71. PMID: 22492018 DOI: 10.22203/ecm.v023a20.
19.                                Ozaki A, Tsunoda M, Kinoshita S, Saura R. Role of fracture hematoma and periosteum during fracture healing in rats: interaction of fracture hematoma and the periosteum in the initial step of the healing process. J Orthop Sci. 2000; 5(1):64-70. PMID: 10664441 DOI: 10.1007/s007760050010.
20.                Oryan A, Bigham-Sadegh A, Monazzah S. Fish bone versus fish demineralized bone matrix (vertebra) effects on healing of experimental radial defect in rat model. Comparat Clin Pathol. 2016; 25(5):981-5.
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(4):540-8. PMID: 8150821 DOI: 10.2106/00004623-199404000-00008.
22.                Tsunoda M, Mizuno K, Matsubara T. The osteogenic potential of fracture hematoma and its mechanism on bone formation--through fracture hematoma culture and transplantation of freeze-dried hematoma. Kobe J Med Sci. 1993; 39(1):35-50. PMID: 8366663
23.                                Grundnes O, Reikerås O. The importance of the hematoma for fracture healing in rats. Acta Orthop Scand. 1993; 64(3):340-2. PMID: 8322595 DOI: 10.3109/17453679308993640.
24.                                Grundnes O, Reikerås O. The role of hematoma and periosteal sealing for fracture healing in rats. Acta Orthop Scand. 1993; 64(1):47-9. PMID: 8451946 DOI: 10.3109/17453679308994527.
25.                Kolar P, Gaber T, Perka C, Duda GN, Buttgereit F. Human early fracture hematoma is characterized by inflammation and hypoxia. Clin Orthop Relat Res. 2011; 469(11):3118-26. PMID: 21409457 PMCID: PMC3183184 DOI: 10.1007/s11999-011-1865-3.
26.                                Schell H. Peters A. Duda G. et al. Removal of fracture hematoma and replacement with fresh hematoma delays bone healing in sheep. Bone. 2012(50):S115.
27.                                Schell H, Duda G, Peters A, Tsitsilonis S, Johnson K. et al. The haematoma and its role in bone healing. J Exp Orthop. 2017;4(1):5. PMID: 28176273 PMCID: PMC5296258 DOI: 10.1186/s40634-017-0079-3.
28.                                Golub LM, Ramamurthy N, McNamara TF, Greenwald RA, Rifkin BR. Tetracyclines inhibit connective tissue breakdown: new therapeutic implications for an old family of drugs. Crit Rev Oral Biol Med. 1991; 2(3):297-321. PMID: 1654139 DOI: 10.1177/10454411910020030201.
 

Home

Submit Manuscript

Contact Us