Dual-delivery of vancomycin and icariin from an injectable calcium phosphate cement-release system for controlling infection and improving bone healing

Huang,Jian-Guo; Pang,Long; Chen,Zhi-Rong; Tan,Xi-Peng

doi:10.3892/mmr.2013.1624

Dual-delivery of vancomycin and icariin from an injectable calcium phosphate cement-release system for controlling infection and improving bone healing

Authors:
- Jian-Guo Huang
- Long Pang
- Zhi-Rong Chen
- Xi-Peng Tan
View Affiliations

Affiliations: Orthopaedics Department Ward 3, General Hospital of Ningxia Medical University, Yinchuan, Xingqing 750004, P.R. China
Published online on: August 9, 2013 https://doi.org/10.3892/mmr.2013.1624
Pages: 1221-1227

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Infectious bone diseases following severely contaminated open fractures are frequently encountered in clinical practice. It is difficult to successfully repair bone and control infection at the same time. To identify a better treatment method, we prepared a dual-drug release system that was comprised of icariin (IC, a natural osteoinductive molecule), vancomycin (VA) and injectable calcium phosphate cement (CPC). The ultrastructure of the dual-drug release system was evaluated by scanning electron microscopy and the biocompatibility was assessed by cell culture. In addition, the release kinetics of IC and VA were respectively investigated by using high‑performance liquid chromatography. Finally, this system was used to repair Staphylococcus aureus-contaminated bone defects in a rabbit model. Twelve weeks after the implantation of IC-VA/CPC, the contaminated bone defects were completely repaired, with significantly improved formation of lamellar bone and recanalization of the marrow cavity compared with the controls (CPC without antibiotics or osteoinductive agent). These results demonstrate that this dual-drug release system, with its concomitant antibiotic and osteoinductive properties, has significant potential for the treatment of contaminated bone injury or infectious bone disease.

View Figures

View References

1	Bi L, Hu Y, Fan H, Meng G, Liu J, Li D and Lv R: Treatment of contaminated bone defects with clindamycin-reconstituted bone xenograft-composites. J Biomed Mater Res B Appl Biomater. 82:418–427. 2007. View Article : Google Scholar : PubMed/NCBI
2	Korkusuz F, Korkusuz P, Eksioglu F, Gursel I and Hasirci V: In vivo response to biodegradable controlled antibiotic release systems. J Biomed Mater Res. 55:217–228. 2001. View Article : Google Scholar : PubMed/NCBI
3	Shinto Y, Uchida A, Korkusuz F, Araki N and Ono K: Calcium hydroxyapatite ceramic used as a delivery system for antibiotics. J Bone Joint Surg Br. 74:600–604. 1992.PubMed/NCBI
4	Cornell CN, Tyndall D, Waller S, Lane JM and Brause BD: Treatment of experimental osteomyelitis with antibioticim-pregnated bone graft substitute. J Orthop Res. 11:619–626. 1993. View Article : Google Scholar : PubMed/NCBI
5	Moehring HD, Gravel C, Chapman MW and Olson SA: Comparison of antibiotic beads and intravenous antibiotics in open fractures. Clin Orthop Relat Res. 372:254–261. 2000. View Article : Google Scholar : PubMed/NCBI
6	Guelcher SA, Brown KV, Li B, Guda T, Lee BH and Wenke JC: Dual-purpose bone grafts improve healing and reduce infection. J Orthop Trauma. 25:477–482. 2011. View Article : Google Scholar : PubMed/NCBI
7	Bi L, Cheng W, Fan H and Pei G: Reconstruction of goat tibial defects using an injectable tricalcium phosphate/chitosan in combination with autologous platelet-rich plasma. Biomaterials. 31:3201–3211. 2010. View Article : Google Scholar : PubMed/NCBI
8	Cui G, Li J, Lei W, Bi L, Tang P, Liang Y, Tao S and Wang Y: The mechanical and biological properties of an injectable calcium phosphate cement-fibrin glue composite for bone regeneration. J Biomed Mater Res B Appl Biomater. 92:377–385. 2010.PubMed/NCBI
9	Urabe K, Naruse K, Hattori H, Hirano M, Uchida K, Onuma K, Park HJ and Itoman M: In vitro comparison of elution characteristics of vancomycin from calcium phosphate cement and polymethylmethacrylate. J Orthop Sci. 14:784–793. 2009. View Article : Google Scholar : PubMed/NCBI
10	Okada M, Sangadala S, Liu Y, Yoshida M, Reddy BV, Titus L and Boden SD: Development and optimization of a cell-based assay for the selection of synthetic compounds that potentiate bone morphogenetic protein-2 activity. Cell Biochem Funct. 27:526–534. 2009. View Article : Google Scholar : PubMed/NCBI
11	Fan JJ, Cao LG, Wu T, Wang DX, Jin D, Jiang S, Zhang ZY, Bi L and Pei GX: The dose-effect of icariin on the proliferation and osteogenic differentiation of human bone mesenchymal stem cells. Molecule. 16:10123–10133. 2011. View Article : Google Scholar : PubMed/NCBI
12	Zhao J, Ohba S, Komiyama Y, Shinkai M, Chung UI and Nagamune T: Icariin: a potential osteoinductive compound for bone tissue engineering. Tissue Eng Part A. 16:233–243. 2010. View Article : Google Scholar : PubMed/NCBI
13	Jiang F, Wang XL, Wang NL and Yao XS: Two new flavonol glycosides from Epimedium koreanum Nakai. J Asian Nat Prod Res. 11:401–409. 2009. View Article : Google Scholar : PubMed/NCBI
14	Nian H, Ma MH, Nian SS and Xu LL: Antiosteoporotic activity of icariin in ovariectomized rats. Phytomedicine. 16:320–326. 2009. View Article : Google Scholar : PubMed/NCBI
15	Zhao J, Ohba S, Shinkai M, Chung UI and Nangamue T: Icariin induces osteogenic differentiation in vitro in a BMP-and Runx2-dependent manner. Biochem Biophys Res Commun. 369:444–448. 2008. View Article : Google Scholar : PubMed/NCBI
16	Fan J, Bi L, Wu T, Cao L, Wang D, Nan K, Chen J, Jin D, Jiang S and Pei G: A combined chitosan/nano-size hydroxyapatite system for the controlled release of icariin. J Mater Sci Mater Med. 23:399–407. 2012. View Article : Google Scholar : PubMed/NCBI
17	Bitar M, Friederici V, Imgrund P, Brose C and Bruinink A: In vitro bioactivity of micro metal injection moulded stainless steel with defined surface features. Eur Cell Mater. 23:333–347. 2012.PubMed/NCBI
18	Li HB and Chen F: Separation and purification of epimedin A, B, C, and icariin from the medicinal herb Epimedium brevicornum maxim by dual-mode HSCCC. J Chromatogr Sci. 47:337–340. 2009. View Article : Google Scholar : PubMed/NCBI
19	Larsson S and Bauer TW: Use of injectable calcium phosphate cement for fracture fixation: a review. Clin Orthop Relat Res. 395:23–32. 2002. View Article : Google Scholar : PubMed/NCBI
20	International Organization for Standardization. ISO 10993-12:2007: Biological evaluation of medical devices. Part 12: Sample preparation and reference materials. ISO; Geneva, Switzerland: 2007
21	Yang L, Wang NL and Cai GP: Maohuoside A promotes osteogenesis of rat mesenchymal stem cells via BMP and MAPK signaling pathways. Mol Cell Biochem. 358:37–44. 2011. View Article : Google Scholar : PubMed/NCBI
22	Melicherčík P, Jahoda D, Nyč O, Klapková E, Barták V, Landor I, Pokorný D, Judl T and Sosna A: Bone grafts as vancomycin carriers in local therapy of resistant infections. Folia Microbiol (Praha). 57:459–462. 2012.PubMed/NCBI
23	Bert F, Leflon-Guibout V, Le GJ, Bourdon N and Nicolas MH: Emergence of vancomycin-dependent enterococci following glycopeptide therapy: case report and review. Pathol Biol (Paris). 57:56–60. 2009.(In French).