Release of antibiotics from the materials for postosteomyelitic bone defect filling

Introduction The search for materials for bone defect filling that would provide a release of antibiotics in therapeutic levels over a long period is a pressing issue in the treatment of patients with osteomyelitis.

The purpose of the work was to compare the kinetics of antibiotic release from materials based on polyurethane polymers for filling post-osteomyelitic bone defects.

Materials and methods A comparative in vitro analysis of the kinetic release of cefotaxime, vancomycin, and meropenem from two materials was performed: one was based on polyurethane polymers (RK series) and the other on polymethyl methacrylate (PMMA series). In each series, antibiotics were added to the original materials in three proportions: polymer/ antibiotic — 10:1 (group 1); 10:0.5 (group 2), and 10:0.25 (group 3). The samples were incubated in 10 ml of saline at 37 °C. The incubation solution was changed daily during the first week, and then once a week. Six samples were incubated in each group.

Results It was revealed that the volume of eluted cefotaxime in the PMMA series was higher than in the RK series for  all  antibiotic concentrations. In turn, for vancomycin and meropenem, it was observed only for group 1 samples. For groups 0.5 and 0.25, a larger volume of released antibiotics was noted in the RK series than in the PMMA series. It was found that in the RK series, the release of vancomycin and cefotaxime in an effective (therapeutic) concentration was more prolonged. In the RK series, there was prolonged release of effective concentrations but in a smaller volume of released antibiotic than in the PMMA series.

Discussion Each material showed its own antibiotic elution profile and each of them may have its own indications. The RK-based material has advantages in terms of the duration of antibiotic elution in therapeutic doses.

Conclusion The release of the studied antibiotics in effective concentrations from the material based on polyurethane polymers is longer than from the PMMA-based material.

1. Afanasyev AV, Bozhkova SA, Artyukh VA et al. Synthetic bone replacement materials used for one-stage treatment of chronic osteomyelitis. Genij Ortopedii. 2021;27(2):232-236. 2021;27(2):232-236. doi: 10.18019/1028-4427-2021-27-2-232-236

2. Liu Y, He L, Cheng L, et al. Enhancing Bone Grafting Outcomes: A Comprehensive Review of Antibacterial Artificial Composite Bone Scaffolds. Med Sci Monit. 2023;29:e939972. doi: 10.12659/MSM.939972

3. Cara A, Ferry T, Laurent F, Josse J. Prophylactic Antibiofilm Activity of Antibiotic-Loaded Bone Cements against GramNegative Bacteria. Antibiotics (Basel). 2022;11(2):137. doi: 10.3390/antibiotics11020137

4. Liu Y, Li X, Liang A. Current research progress of local drug delivery systems based on biodegradable polymers in treating chronic osteomyelitis. Front Bioeng Biotechnol. 2022;10:1042128. doi: 10.3389/fbioe.2022.1042128

5. Wassif RK, Elkayal M, Shamma RN, Elkheshen SA. Recent advances in the local antibiotics delivery systems for management of osteomyelitis. Drug Deliv. 2021;28(1):2392-2414. doi: 10.1080/10717544.2021.1998246

6. Chen P, Chen B, Liu N, et al. Global research trends of antibiotic-loaded bone cement: A bibliometric and visualized study. Heliyon. 2024;10(17):e36720. doi: 10.1016/j.heliyon.2024.e36720

7. Tapalski DV, Volotovski PA, Kozlova AI, Sitnik AA. Antibacterial Activity of Antibiotic-Impregnated Bone Cement Based Coatings Against Microorganisms with Different Antibiotic Resistance Levels. Traumatology and Orthopedics of Russia. 2018;24(4):105-110. (In Russ.) doi: 10.21823/2311-2905-2018-24-4-105-110

8. Wall V, Nguyen TH, Nguyen N, Tran PA. Controlling Antibiotic Release from Polymethylmethacrylate Bone Cement. Biomedicines. 2021;9(1):26. doi: 10.3390/biomedicines9010026

9. Chen L, Lin X, Wei M, et al. Hierarchical antibiotic delivery system based on calcium phosphate cement/montmorillonitegentamicin sulfate with drug release pathways. Colloids Surf B Biointerfaces. 2024;238:113925. doi: 10.1016/j.colsurfb.2024.113925

10. Jin Y, Liu H, Chu L, et al. Initial therapeutic evidence of a borosilicate bioactive glass (BSG) and Fe3O4 magnetic nanoparticle scaffold on implant-associated Staphylococcal aureus bone infection. Bioact Mater. 2024;40:148-167. doi: 10.1016/j.bioactmat.2024.05.040

11. Wathoni N, Herdiana Y, Suhandi C, et al. Chitosan/Alginate-Based Nanoparticles for Antibacterial Agents Delivery. Int J Nanomedicine. 2024;19:5021-5044. doi: 10.2147/IJN.S469572

12. Balyazin-Parfenov IV, Balyazin VA, Zaitsev VD, et al. Long-term results of allocranioplasty using individual biopolymer osteointegrable implants made of “Recost-M” material. Russian Neurosurgical Journal named after Professor A.L. Polenov. 2024;16(2):6-15. (In Russ.) doi: 10.56618/2071-2693_2024_16_2_6

13. Kolmogorov YuN, Uspensky IV, Maslov AN, et al. Rekost-M Bone Replacement Implants Based on 3D Modeling for Closing Post-Craniotomy Skull Defects: Pre-Clinical and Clinical Studies. Modern Technologies in Medicine. 2018;10(3):95-103. (In Russ.) doi: 10.17691/stm2018.10.3.11

14. Madadi AK, Sohn MJ. Pharmacokinetic Interpretation of Applying Local Drug Delivery System for the Treatment of Deep Surgical Site Infection in the Spine. Pharmaceutics. 2024;16(1):94. doi: 10.3390/pharmaceutics16010094

15. Kai KC, Borges R, Pedroni ACF, et al. Tricalcium phosphate-loaded injectable hydrogel as a promising osteogenic and bactericidal teicoplanin-delivery system for osteomyelitis treatment: An in vitro and in vivo investigation. Biomater Adv. 2024;164:213966. doi: 10.1016/j.bioadv.2024.213966

16. Mabroum H, Elbaza H, Ben Youcef H, et al. Design of antibacterial apatitic composite cement loaded with Ciprofloxacin: Investigations on the physicochemical Properties, release Kinetics, and antibacterial activity. Int J Pharm. 2023;637:122861. doi: 10.1016/j.ijpharm.2023.122861

17. Noukrati H, Hamdan Y, Marsan O, et al. Sodium fusidate loaded apatitic calcium phosphates: Adsorption behavior, release kinetics, antibacterial efficacy, and cytotoxicity assessment. Int J Pharm. 2024;660:124331. doi: 10.1016/j.ijpharm.2024.124331

18. Visan AI, Negut I. Development and Applications of PLGA Hydrogels for Sustained Delivery of Therapeutic Agents. Gels. 2024;10(8):497. doi: 10.3390/gels10080497

19. Popkov AV, Kononovich NV, Popkov DA. et al. Induction of bactericidal activity by degradable implants. Genij Ortopedii. 2023;29(6):596-601. doi: 10.18019/1028-4427-2023-29-6-596-601

20. Lan Z, Guo L, Fletcher A, et al. Antimicrobial hydrogel foam dressing with controlled release of gallium maltolate for infection control in chronic wounds. Bioact Mater. 2024;42:433-448. doi: 10.1016/j.bioactmat.2024.08.044

21. Jarman E, Burgess J, Sharma A, et al. Human-Derived collagen hydrogel as an antibiotic vehicle for topical treatment of bacterial biofilms. PLoS One. 2024;19(5):e0303039. doi: 10.1371/journal.pone.0303039

22. Sevost’yanov MA, Fedotov AYu, Nasakina EO, et al. Kinetics of antibiotic release from biodegradable biopolymer membranes based on chitosan. Reports of the Academy of Sciences. 2015:465(2);194-197. (In Russ.) doi: 10.7868/S086956521532016X

23. Sheehy EJ, von Diemling C, Ryan E, et al. Antibiotic-eluting scaffolds with responsive dual-release kinetics facilitate bone healing and eliminate S. aureus infection. Biomaterials. 2025;313:122774. doi: 10.1016/j.biomaterials.2024.122774

24. Li X, Wei A, Zhao H, et al A carboxymethyl-resistant starch/polyacrylic acid semi-IPN hydrogel with excellent adhesive and antibacterial properties for peri-implantitis prevention. Colloids Surf B Biointerfaces. 2024;242:114082. doi: 10.1016/j.colsurfb.2024.114082

25. Nguyen VN, Wang SL, Nguyen TH, et al. Preparation and Characterization of Chitosan/Starch Nanocomposites Loaded with Ampicillin to Enhance Antibacterial Activity against Escherichia coli. Polymers (Basel). 2024;16(18):2647. doi: 10.3390/polym16182647

26. Sahu KM, Biswal A, Manisha U, Swain SK. Synthesis and drug release kinetics of ciprofloxacin from polyacrylamide/ dextran/carbon quantum dots (PAM/Dex/CQD) hydrogels. Int J Biol Macromol. 2024;269(Pt 2):132132. doi: 10.1016/j.ijbiomac.2024.132132

27. Wang G, An S, Huang S, et al. Fabrication, optimization, and in vitro validation of penicillin-loaded hydrogels for controlled drug delivery. J Biomater Sci Polym Ed. 2024:1-21. doi: 10.1080/09205063.2024.2387953

28. Shi Y, Wang L, Song S, et al. Controllable Silver Release for Efficient Treatment of Drug-Resistant Bacterial-Infected Wounds. Chembiochem. 2024;25(16):e202400406. doi: 10.1002/cbic.202400406

29. Galván-Romero V, Gonzalez-Salazar F, Vargas-Berrones K, et al. Development and evaluation of ciprofloxacin local controlled release materials based on molecularly imprinted polymers. Eur J Pharm Biopharm. 2024;195:114178. doi: 10.1016/j.ejpb.2024.114178

30. Osak P, Skwarek S, Łukowiec D, et al. Preparation and Characterization of Oxide Nanotubes on Titanium Surface for Use in Controlled Drug Release Systems. Materials (Basel). 2024;17(15):3753. doi: 10.3390/ma17153753

31. Huang Z, Li Y, Yin W, et al. A magnetic-guided nano-antibacterial platform for alternating magnetic field controlled vancomycin release in staphylococcus aureus biofilm eradication. Drug Deliv Transl Res. 2024. doi: 10.1007/s13346-024-01667-x

32. Qi H, Wang B, Wang M, et al. A pH/ROS-responsive antioxidative and antimicrobial GelMA hydrogel for on-demand drug delivery and enhanced osteogenic differentiation in vitro. Int J Pharm. 2024 Ma;657:124134. doi: 10.1016/j.ijpharm.2024.124134

33. Seidenstuecker M, Hess J, Baghnavi A, et al. Biodegradable composites with antibiotics and growth factors for dual release kinetics. J Mater Sci Mater Med. 2024;35(1):40. doi: 10.1007/s10856-024-06809-8.