Analysis of various models of chronic osteomyelitis in experimental animals

Alexander Rudenko 1 * , Berik Tuleubayev 1 2, Dina Saginova 2, Amina Koshanova 2, Konstantin Vorobyov 3
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1 Department of Emergency Trauma, Multifunctional Regional Center of Traumatology and Orthopedics named after Professor H.Zh.Makazhanov, Karaganda, Kazakhstan
2 Department of Surgical Diseases, Karaganda Medical University, Karaganda, Kazakhstan
3 “Tissue Bank” Laboratory, National Medical Research Center for Traumatology and Orthopedics named after N.N. Priorov, Saint-Petersburg, Russia
* Corresponding Author
J CLIN MED KAZ, Volume 19, Issue 4, pp. 21-27. https://doi.org/10.23950/jcmk/12276
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ABSTRACT

Introduction: Chronic osteomyelitis occurs in 3-25% of cases after open fractures and in 1-8% of cases after surgical treatment of closed fractures. It accounts for 3 to 10% in the structure of purulent surgical diseases. Traditional treatment methods many times do not provide a complete cure for osteomyelitis. In modern medicine, many experimental models have been created on different types of laboratory animals in order to reproduce the model of chronic osteomyelitis and subsequently improve its therapy. Of all the experimental animals, we chose rabbits for the application of the developed method for the treatment of chronic osteomyelitis and for the selection of the optimal model of bone tissue suppuration.
The objective was to conduct a clinical, radiological and histological analysis of various models of chronic osteomyelitis in experimental animals.
Materials and methods: The experiment was carried out on 90 outbred rabbits. All rabbits were randomly divided into 5 groups. The rabbits were kept in a room with controlled temperature (16-21 °C) and relative humidity (45-65%). The rabbits were placed in special cages – 2-3 rabbits per each. Surgical intervention was performed under general anesthesia. Surgical access was made along the anterior surface of the distal metaepiphyseal area of the left femur. All animals were intraosseus injected with Staphylococcus aureus as an infectious agent. The development of chronic osteomyelitis was assessed by clinical, radiological, microbiological, histological and statistical methods.
Results: The study showed that X-ray and histological methods play an important role in the analysis of experimental models. The signs of osteomyelitis development can be seen on the 14th day after the operation with the help of the X-ray method, while wound healing, weight and temperature cannot be indicators. According to the results of the experiment, the signs of chronic osteomyelitis developed in all 5 groups, but its activity was different. Histological examination showed that osteomyelitis developed differently in different groups, fibrosis developed unevenly.
Keywords: bone infection, Staphylococcus aureus, rabbits, osteomyelitis model, experimental model

CITATION

Rudenko A, Tuleubayev B, Saginova D, Koshanova A, Vorobyov K. Analysis of various models of chronic osteomyelitis in experimental animals. J CLIN MED KAZ. 2022;19(4):21-7. https://doi.org/10.23950/jcmk/12276

REFERENCES

  • Saginova D.A. Lokal'noe ispol'zovanie biodegradiruemyh materialov v lechenii hronicheskogo osteomielita (obzor literatury) (Local Use Of Biodegradable Materials In The Treatment Of Chronic Osteomyelitis (Literature Review) [in Russian]. Vestnik KazNMU. 2018; 1:199–204.
  • Derkachev V.S., Alekseev S.A., Bordakov V.N., Elin I.A., Derkachev D.V. K voprosu o kompleksnom lechenii hronicheskogo posttravmaticheskogo osteomielita (To the question of complex treatment of chronic post-traumatic osteomyelitis) [in Russian]. Travmatologija zhәne ortopedija. 2015; 3(4):43–44.
  • Konev V.A., Bozhkova S.A., Netyl'ko G.I., Afanas'ev A.V., Rumakin V.P., Poljakova E.M., Rukina A.N., Parfeev D.G. Rezul'taty primenenija fosfomicina dlja impregnacii osteozameshhajushhih materialov pri lechenii hronicheskogo osteomielita (The results of the use of fosfomycin for the impregnation of osteoplastic materials in the treatment of chronic osteomyelitis) [in Russian]. Travmatologija i ortopedija Rossii. 2016; 2(22):43–54.
  • Privol'nev V.V., Rodin A.V., Karakulina E.V. Mestnoe primenenie antibiotikov v lechenii infekcij kostnoj tkani (Topical use of antibiotics in the treatment of bone infections) [in Russian]. Klin. Mikrobiol. Antimikrob. Himioter. 2012; 14(2):118–121.
  • Clement L.K. Chia, Vishal G. Shelat, Wilson Low, Sheena George, Jaideep R. The Use of Collatamp G, Local GentamicinCollagen Sponge, in Reducing Wound Infection. Int Surg. 2014; 99(5):565–570. https://doi.org/10.9738/INTSURG-D-13-00171.1
  • Garcia E.J., Sieg R.N., Abdelgawad A.A. Local application of free antibiotic powder in the treatment of osteomyelitis in a rat model. Orthopedics. 2013; 36(8):986–989. https://doi.org/10.3928/01477447-20130724-11
  • Fleiter N., Walter G., Bsebeck H., Vogt S., Bchner H., Hirschberger W., Hoffmann R. Clinical use and safety of a novel gentamicin-releasing resorbable bone graft substitute in the treatment of osteomyelitis/osteitis. Bone Joint Res. 2014; 3:223–229. https://doi.org/10.1302/2046-3758.37.2000301
  • Uskoković V. Nanostructured Platforms for the Sustained and Local Delivery of Antibiotics in the Treatment of Osteomyelitis. Crit. Rev. Ther. Drug Carrier Syst. 2015; 32(1):51–59. https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2014010920
  • Uskoković V., Desai T.A. In vitro analysis of nanoparticulate hydroxyapatite/chitosan composites as potential drug delivery platforms for the sustained release of antibiotics in the treatment of osteomyelitis. J Pharm Sci. 2014; 103(2):567–579. https://doi.org/10.1002/jps.23824
  • Xing J., Hou T., Luobu B., Luo F., Chen Q., Li Z., Jin H., Xu J. Anti-infection tissue engineering construct treating osteomyelitis in rabbit tibia. Tissue Eng Part A. 2013;19(1-2):255–263. https://doi.org/10.1089/ten.tea.2012.0262
  • Tan H.L., Ao H.Y., Ma R., Lin W.T., Tang T.T. In vivo effect of quaternized chitosan-loaded polymethylmethacrylate bone cement on methicillin-resistant Staphylococcus epidermidis infection of the tibial metaphysis in a rabbit model. Antimicrob Agents Chemother. 2014; 58(10):6016–6023. https://doi.org/10.1128/AAC.03489-14
  • Zhivcov O.P., Mitrofanov V.N., Burgov S.N., Gordinskaja N.A. Jeksperimental'naja Model' Hronicheskoj Gnojnoj Kostnoj Polosti (Experimental Model of Chronic Purulent Bone Cavity) [in Russian]. Sovremennye problemy nauki i obrazovanija. 2015;6:URL:http://www.science-education.ru/ru/article/view?id=23642.
  • Chernigova, S.V., Bajzyhanov S.K., Chernigov Ju.V. Ocenka klinicheskogo statusa krolikov s ostrym travmaticheskim osteomielitom trubchatyh kostej v jeksperimente (The clinical status of rabbits with acute traumatic osteomyelitis of the tubular bones in an experiment) [in Russian]. Voprosy normativno-pravovogo regulirovanija v veterinarii. 2013;3:131–132.
  • Patel M., Rojavin Y., Jamali A.A., Wasielewski S.J., Salgado C.J. Animal Models for the Study of Osteomyelitis. Semin Plast Surg. 2009; 23(2):148–154. https://doi.org/10.1055/s-0029-1214167
  • Bottagisio M., Lovati A.B. A review on animal models and treatments for the reconstruction of Achilles and flexor tendons. J Mater Sci Mater Med. 2017; 28(3):45. https://doi.org/10.1007/s10856-017-5858-y
  • Lovati A.B., Bottagisio M., de Vecchi E., Gallazzi E., Drago L. Animal Models of Implant-Related Low-Grade Infections. A Twenty-Year Review. Adv Exp Med Biol. 2017; 971:29–50. https://doi.org/10.1007/5584_2016_157
  • Coman C., Carmen C., Florica B., Ene V., Marius B. Histological Assessment Of An Experimental Model Of Human Osteomyelitis In Rabbits. Sciendo. 2013:432–437. https://doi.org/10.2478/alife-2018-0065
  • Amineva P.G., Rudnov V.A., Karmackih O.G., Nevskaja N.N., Bel'skij D.V., Ivanova N.A. Rezul'taty identifikacii bakterij iz polozhitel'nyh gemokul'tur pacientov mnogoprofil'nogo stacionara s pomoshh'ju MALDI-TOF mass-spektrometrii (The results of the identification of bacteria from positive hemocultures of patients in a multidisciplinary hospital using MALDI-TOF mass spectrometry) [in Russian]. Klinicheskaja mikrobiologija i antimikrobnaja himioterapija. 2018; 4(20):381–386.
  • Scheman L., Janota M., Lewin P. The production of experimental osteomyelitis: preliminary report. J Am Med Assoc. 1941; 117:1525–1529. https://doi.org/10.1001/jama.1941.02820440033008
  • Norden C.W., Kennedy E. Experimental osteomyelitis. I. A description of the model. J Infect Dis. 1970; 122:410–418. https://doi.org/10.1093/infdis/122.5.410
  • Saleh-Mghir A., Dumitrescu O., Dinh A., Boutrad Y., Massias L. Ceftobiprole efficacy in vitro against Panton-Valentine leucocidin production and in vivo against community-associated methicillin-resistant Staphylococcus aureus osteomyelitis in rabbits. Antimicrob Agents Chemother. 2012; 56:6291–6297. https://doi.org/10.1128/AAC.00926-12
  • Jia W.T., Luo S.H., Zhang C.Q., Wang J.Q. In vitro and in vivo efficacies of teicoplanin-loaded calcium sulfate for treatment of chronic methicillin-resistant Staphylococcus aureus osteomyelitis. Antimicrob Agents Chemother. 2010; 54:170–176. https://doi.org/10.1128/AAC.01122-09
  • Hui T., Yongqing X., Tiane Z., Gang L., Yonggang Y. Treatment of osteomyelitis by liposomal gentamicin-impregnated calcium sulfate. Arch Orthop Trauma Surg. 2009; 129:1301–1308. https://doi.org/10.1007/s00402-008-0782-8
  • Jiang J.L., Li Y.F., Fang T.L., Zhou J., Li X.L. Vancomycinloaded nano-hydroxyapatite pellets to treat MRSA-induced chronic osteomyelitis with bone defect in rabbits. Inflamm Res. 2012; 61:207–215. https://doi.org/10.1007/s00011-011-0402-x
  • Shi P., Zuo Y., Li X., Zou Q., Liu H. Gentamicin-impregnated chitosan/nanohydroxyapatite/ethyl cellulose microspheres granules for chronic osteomyelitis therapy. J Biomed Mater Res A. 2010; 93:1020–1031. https://doi.org/10.1002/jbm.a.32598
  • Wang Q., Chen C., Liu W., He X., Zhou N. Levofloxacin loaded mesoporous silica microspheres/nano-hydroxyapatite/polyurethane composite scaffold for the treatment of chronic osteomyelitis with bone defects. Sci Rep. 2017; 7:41808. https://doi.org/10.1038/srep41808
  • Xing J., Hou T., Luobu B., Luo F., Chen Q. Anti-infection tissue engineering construct treating osteomyelitis in rabbit tibia. Tissue Eng Part A. 2013; 19:255–263. https://doi.org/10.1089/ten.tea.2012.0262
  • Yan L., Jiang D.M., Cao Z.D., Wu J., Wang X. Treatment of Staphylococcus aureus -induced chronic osteomyelitis with bone-like hydroxyapatite / poly amino acid loaded with rifapentine microspheres. Drug Des Devel Ther. 2015; 9:3665–3676. https://doi.org/10.2147/DDDT.S84486
  • Yin L.Y., Calhoun J.H., Thomas J.K., Shapiro S., Schmitt-Hoffmann A. Efficacies of ceftobiprole medocaril and comparators in a rabbit model of osteomyelitis due to methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2008; 52:1618–1622. https://doi.org/10.1128/AAC.00638-07
  • Zhang Y., Liang R.J., Xu J.J., Shen L.F., Gao J.Q. Efficient induction of antimicrobial activity with vancomycin nanoparticle-loaded poly(trimethylene carbonate) localized drug delivery system. Int J Nanomedicine. 2017; 12:1201–1214. https://doi.org/10.2147/IJN.S127715
  • Zhou J., Zhou X.G., Wang J.W., Zhou H., Dong J. Treatment of osteomyelitis defects by a vancomycin-loaded gelatin/β-tricalcium phosphate composite scaffold. Bone Joint Res. 2018; 7:46–57. https://doi.org/10.1302/2046-3758.71.BJR-2017-0129.R2
  • Rodeheaver G.T., Rukstalis D., Bono M., Bellamy W. A new model of bone infection used to evaluate the efficacy of antibiotic-impregnated polymethylmethacrylate cement. Clin Orthop Relat Res. 1983; 178:303-311. https://doi.org/10.1097/00003086-198309000-00042
  • Jacob E., Arendt D.M., Brook I., Durham L.C., Falk M.C., Schaberg S.J. Enzyme-linked immunosorbent assay for detection of antibodies to Staphylococcus aureus cell walls in experimental osteomyelitis. J Clin Microbiol. 1985; 22:547–552. https://doi.org/10.1128/jcm.22.4.547-552.1985
  • Schulz S., Steinhart H., Mutters R. Chronic osteomyelitis in a new rabbit model. J Invest Surg. 2001; 14:121–131. https://doi.org/10.1177/039139880602900411
  • Rutledge B., Huyette D., Day D., Anglen J. Treatment of osteomyelitis with local antibiotics delivered via bioabsorbable polymer. Clin Orthop Relat Res. 2003; 411:280–287. https://doi.org/10.1097/01.blo.0000065836.93465.ed
  • Lazarettos J., Efstathopoulos N., Papagelopoulos P.J., Savvidou O.D., Kanellakopoulou K., Giamarellou H., Giamarellos-Bourboulis E.J., Nikolaou V., Kapranou A., Papalois A. A bioresorbable calcium phosphate delivery system with teicoplanin for treating MRSA osteomyelitis. Clin Orthop Relat Res. 2004; 23:253–258. https://doi.org/10.1097/01.blo.0000127422.06956.35
  • Gratz S., Behe M., Boerman O.C., Kunze E., Schulz H., Eiffert H., O’Reilly T., Behr T.M., Angerstein C., Nebendahl K. (99m)Tc-E-selectin binding peptide for imaging acute osteomyelitis in a novel rat model. Nucl Med Commun. 2001; 22:1003–1013. https://doi.org/10.1097/01.blo.0000127422.06956.35