Skip to main content
Log in

Study on critical-sized ultra-high molecular weight polyethylene wear particles loaded with alendronate sodium: in vitro release and cell response

  • Clinical Applications of Biomaterials
  • Original Research
  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

The aim of this study was to investigate the in vitro release and the effect of RAW 264.7 macrophages of critical-sized wear particles of ultra-high molecular weight polyethylene (UHMWPE) loaded with alendronate sodium (ALN), one of the most effective drugs to treat osteoporosis in clinic. The critical-sized UHMWPE-ALN 0.5 wt.% wear particles were prepared by vacuum gradient filtration combined with Pluronic F-68. In vitro release of ALN from critical-sized UHMWPE-ALN wear particles was investigated in phosphate buffered saline (PBS) at 37 °C with a shaker. Cell morphology, proliferation, lactate dehydrogenase (LDH) leakage and secretions of cytokines were evaluated after co-cultured with critical-sized UHMWPE-ALN wear particles in vitro. Results showed that ALN released from critical-sized UHMWPE-ALN wear particles included burst release and slow release in vitro. Macrophages would be chemotaxis and aggregated around the critical-sized UHMWPE-ALN or UHMWPE wear particle, which was phagocytosed with time. The proliferation of macrophages co-cultured with critical-sized UHMWPE-ALN wear particles was significantly decreased compared with that of critical-sized UHMWPE group. Meanwhile, the critical-sized UHMWPE-ALN wear particles significantly induced the LDH leakage of macrophages, which indicated the cell death. The death of macrophages induced by ALN was one of pathways to inhibit their proliferation. The secretions of cytokines (interleukin-6 and tumor necrosis factor-alpha) in critical-sized UHMWPE-ALN group were significantly lower than those in critical-sized UHMWPE group due to the released ALN. The present results suggested that UHMWPE-ALN had the potential application in clinic to treat osteolysis induced by wear particles.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Goodman SB, Gómez Barrena E, Takagi M, Konttinen YT. Biocompatibility of total joint replacements: a review. J Biomed Mater Res A. 2009;90:603–18.

    Article  Google Scholar 

  2. Drees P, Eckardt A, Gay RE, Gay S, Huber LC. Mechanisms of disease: molecular insights into aseptic loosening of orthopedic implants. Nat Clin Pract Rheumatol. 2007;3:165–71.

    Article  Google Scholar 

  3. Dion NT, Bragdon C, Muratoglu O, Freiberg AA. Durability of highly cross-linked polyethylene in total hip and total knee arthroplasty. Orthop Clin N Am. 2015;46:321–7.

    Article  Google Scholar 

  4. Kurtz SM, Gawel HA, Patel JD. History and systematic review of wear and osteolysis outcomes for first-generation highly crosslinked polyethylene. Clin Orthop Relat Res. 2011;469:2262–77.

    Article  Google Scholar 

  5. Wood WJ, Maguire RG, Zhong WH. Improved wear and mechanical properties of UHMWPE-carbon nanofiber composites through an optimized paraffin-assisted melt-mixing process. Compos Part B. 2011;42:584–91.

    Article  Google Scholar 

  6. Deng YL, Xiong DS, Wang K. Biotribological properties of UHMWPE grafted with AA under lubrication as artificial joint. J Mater Sci Mater Med. 2013;24:2085–91.

    Article  Google Scholar 

  7. Shen J, Gao GR, Liu XC, Fu J. Natural polyphenols enhance stability of crosslinked UHMWPE for joint implants. Clin Orthop Relat Res. 2015;473:760–6.

    Article  Google Scholar 

  8. Ingham E, Fisher J. The role of macrophages in osteolysis of total joint replacement. Biomaterials. 2005;26:1271–86.

    Article  Google Scholar 

  9. Hata K, Minoda Y, Ikebuchi M, Mizokawa S, Ohta Y, Miyazaki N, Miyake Y, Nakamura H. In vivo wear particles of remelted highly crosslinked polyethylene after total hip arthroplasty: report of four cases. J Mater Sci Mater Med. 2015;26:133

    Article  Google Scholar 

  10. Moreau MF, Guillet C, Massin P, Chevalier S, Gascan H, Baslé MF, Chappard D. Comparative effects of five bisphosphonates on apoptosis of macrophage cells in vitro. Biochem Pharmacol. 2007;73:718–23.

    Article  Google Scholar 

  11. Jablonski H, Kauther MD, Bachmann HS, Jäeger M, Wedemeyer C. Calcitonin gene-related peptide modulates the production of pro-inflammatory cytokines associated with periprosthetic osteolysis by THP-1 macrophage-like cells. Neuroimmunomodulat. 2015;22:152–65.

    Article  Google Scholar 

  12. Lu YC, Chang TK, Yeh ST, Fang HW, Lin CY, Hsu LI, Huang CH, Huang CH. The potential role of strontium ranelate in treating particle-induced osteolysis. Acta Biomater. 2015;20:147–54.

    Article  Google Scholar 

  13. Zhang YY, Lin Y, Xiao LL, Feng EY, Wang WL, Lin LQ. The effects of icariine concentration on osteoclasts bone resorption induced by titanium particles in vitro. Regen Biomater. 2015;2:197–202.

    Article  Google Scholar 

  14. Cattalini JP, Boccaccini AR, Lucangioli S, Mouriño V. Bisphosphonate-based strategies for bone tissue engineering and orthopedic implants. Tissue Eng Part B Rev. 2012;18:323–40.

    Article  Google Scholar 

  15. Yamazaki T, Yamori M, Yamamoto K, Saito K, Asai K, Sumi E, Goto K, Takahashi K, Nakayama T, Bessho K. Risk of osteomyelitis of the jaw induced by oral bisphosphonates in patients taking medications for osteoporosis: a hospital-based cohort study in Japan. Bone. 2012;51:882–7.

    Article  Google Scholar 

  16. Boanini E, Torricelli P, Gazzano M, Giardino R, Bigi A. Alendronate-hydroxyapatite nanocomposites and their interaction with osteoclasts and osteoblast-like cells. Biomaterials. 2008;29:790–6.

    Article  Google Scholar 

  17. Garbuz DS, Hu YX, Kim WY, Duan K, Masri BA, Oxland TR, Burt H, Wang RZ, Duncan CP. Enhanced gap filling and osteoconduction associated with alendronate-calcium phosphate-coated porous tantalum. J Bone Joint Surg Am. 2008;90:1090–100.

    Article  Google Scholar 

  18. Gong KM, Qu SX, Liu YM, Wang J, Zhang YC, Jiang CX, Shen R. The mechanical and tribological properties of UHMWPE loaded ALN after mechanical activation for joint replacements. J Mech Behav Biomed Mater. 2016;61:334–44.

    Article  Google Scholar 

  19. Qu SX, Bai YL, Liu XM, Fu R, Duan K, Weng J. Study on in vitro release and cell response to alendronate sodium-loaded ultrahigh molecular weight polyethylene loaded with alendronate sodium wear particles to treat the particles-induced osteolysis. J Biomed Mater Res A. 2013;101:394–403.

    Article  Google Scholar 

  20. Yang D, Qu SX, Huang J, Cai ZB, Zhou ZR. Characterization of alendronate sodium-loaded UHMWPE for anti-osteolysis in orthopedic applications. Mater Sci Eng C. 2012;32:83–91.

    Article  Google Scholar 

  21. Hallab NJ, McAllister K, Brady M, Jarman-Smith M. Macrophage reactivity to different polymers demonstrates particle size- and material-specific reactivity: PEEK-OPTIMA® particles versus UHMWPE particles in the submicron, micron, and 10 micron size ranges. J Biomed Mater Res B Appl Biomater. 2012;100:480–92.

    Article  Google Scholar 

  22. Richards L, Brown C, Stone MH, Fisher J, Ingham E, Tipper JL. Identification of nanometre-sized ultra-high molecular weight polyethylene wear particles in samples retrieved in vivo. J Bone Joint Surg Br. 2008;90:1106–13.

    Article  Google Scholar 

  23. Sultana S, Talegaonkar S, Mittal G, Bhatnagar A, Ahmad FJ. Determination of alendronate sodium by box-behnken statistical design. Chromatographia. 2010;72:321–6.

    Article  Google Scholar 

  24. Fang HW, Ho YC, Yang CB, Liu HL, Ho FY, Lu YC, Ma HM, Huang CH. Preparation of UHMWPE particles and establishment of inverted macrophage cell model to investigate wear particles induced bioactivites. J Biochem Biophs Methods. 2006;68:175–87.

    Article  Google Scholar 

  25. Zhang YB, Ali SF, Dervishi E, Xu Y, Li ZR, Casciano D, Biris AS. Cytotoxicity effects of graphene and single-wall carbon nanotubes in neural phaeochromocytoma-derived PC12 cells. ACS Nano. 2010;4:3181–6.

    Article  Google Scholar 

  26. Chang YL, Yang ST, Liu JH, Dong EY, Wang YW, Cao AN, Liu YF, Wang HF. In vitro toxicity evaluation of graphene oxide on A549 cells. Toxicol Lett. 2011;200:201–10.

    Article  Google Scholar 

  27. Huang ZN, Ma T, Ren PG, Smith RL, Goodman SB. Effects of orthopedic polymer particles on chemotaxis of macrophages and mesenchymal stem cells. J Biomed Mater Res A. 2010;94:1264–9.

    Google Scholar 

  28. Alley C, Haggard W, Smith R. Effect of UHMWPE particle size, dose, and endotoxin on in vitro macrophage response. J Long Term Eff Med Implants. 2014;24:45–56.

    Article  Google Scholar 

  29. Bladen CL, Teramura S, Russell SL, Fujiwara K, Fisher J, Ingham E, Tomita N, Tipper JL. Analysis of wear, wear particles, and reduced inflammatory potential of vitamin E ultrahigh-molecular-weight polyethylene for use in total joint replacement. J Biomed Mater Res B Appl Biomater. 2013;101:458–66.

    Google Scholar 

  30. Ge SR, Wang SB, Gitis N, Vinogradov M, Xiao J. Wear behavior and wear debris distribution of UHMWPE against Si3N4 ball in bi-directional sliding. Wear. 2008;264:571–8.

    Article  Google Scholar 

  31. Wu JP, Peng ZX, Tipper J. Mechanical properties and three-dimensional topological characterisation of micron, submicron and nanoparticles from artificial joints. Tribol Lett. 2013;52:449–60.

    Article  Google Scholar 

  32. Berkland C, Pollauf E, Raman C, Silverman R, Kim K, Pack DW. Macromolecule release from monodisperse PLG microspheres: control of release rates and investigation of release mechanism. J Pharm Sci. 2007;96:1176–91.

    Article  Google Scholar 

  33. Evans CE. Bisphosphonates modulate the effect of macrophage-like cells on osteoblast. Int J Biochem Cell Biol. 2002;34:554–63.

    Article  Google Scholar 

  34. Shi XT, Wang YJ, Ren L, Gong YH, Wang DA. Enhancing alendronate release from a novel PLGA/Hydroxyapatite microspheric system for bone repairing applications. Pharm Res. 2009;26:422–30.

    Article  Google Scholar 

  35. Goodman SB, Gibon E, Pajarinen J, Lin TH, Keeney M, Ren PG, Nich C, Yao Z, Egashira K, Yang F, Konttinen YT. Novel biological strategies for treatment of wear particle-induced periprosthetic osteolysis of orthopaedic implants for joint replacement. J R Soc Interface. 2014;11:20130962

    Article  Google Scholar 

  36. Dai M, Jiang C, Liu X, Li Z, Cheng XG, Zou Y, Nie T. Wear particle-mediated expressions of pro-inflammatory cytokines, NF-κB and RANK were impacted by lanthanum chloride in RAW264.7 cells. J Rare Earth. 2013;31:531–40.

    Article  Google Scholar 

Download references

Acknowledgements

The present study was supported by the National Basic Research Program of China (973 Program, 2012CB933602), the National Natural Science Foundation of China (51372210, 51203130, 50975239), the Research Fund for the Doctoral Program of Higher Education of China (20130184110023), the Basic Research Foundation Key Project of Sichuan Province (2016JY0011), the Fundamental Research Funds for the Central Universities, (2682016YXZT11) and the Construction Program for Innovative Research Team of University in Sichuan Province (14TD0050).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shuxin Qu.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, Y., Shi, F., Gong, K. et al. Study on critical-sized ultra-high molecular weight polyethylene wear particles loaded with alendronate sodium: in vitro release and cell response. J Mater Sci: Mater Med 28, 56 (2017). https://doi.org/10.1007/s10856-017-5865-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10856-017-5865-z

Keywords

Navigation