Biofilm-inhibiting and Osseointegration-promoting Orthopedic Implants with Novel Nanocoatings

  • Meng ChenEmail author
  • Hongmin Sun
  • Hongjiao Ouyang
  • John E. Jones
  • Qingsong Yu
  • Yuanxi Xu
  • Shankar Revu


Orthopedic implants are medical devices surgically placed into the body to replace a missing joint or bone or to reinforce a damaged structure. However, there is up to a 28% loosening rate on cementless implanted knee joint prostheses within a 4–10-year period after implant insertion, and a 2–5% infection rate for orthopedic implants (joint prostheses and fracture fixation devices). In the USA, total hip and knee arthroplasties currently account for over one million interventions each year. Due to the enormous size of the patient population with orthopedic implants, even a currently low risk of infection or failure has not only caused many patients to suffer, but it has also incurred huge costs for the associated health care system. Therefore, there is an urgent need to develop a novel dual-functional nanocoating technology with judiciously engineered physicochemical properties to address simultaneously the two critical issues long facing orthopedic implants: lack of integration with bone tissue and biofilm-caused infections for the enhanced success of implants.

We have generated a nanocoating showing a very promising capability of inhibiting biofilm formation by Staphylococcus aureus and Staphylococcus epidermidis, two of the most common biofilm formers on orthopedic implants, and enhancing bone conductivity simultaneously. The dual-functional nanocoatings coming out of our research demonstrated the following unique features for orthopedic implants: (1) inhibit bacterial colonization and concomitantly promote osteoblast functions; (2) generate long-lasting functionalities for practical clinical applications because these nanocoatings are dense and highly cross-linked without substances of low molecular weight; (3) provide needed abrasion resistance for orthopedic implants and ensure strong coating adhesion to the surface; and (4) improve bone integration and reduce device-related infections in the long run.


Anti-biofilm Nanocoating Osseointegration Bone conductivity Staphylococcus aureus Staphylococcus epidermidis Low temperature plasma deposition Dual-function Orthopedic implants Coating adhesion Abrasion resistance Surface chemistry Contact angle Proliferation Differentiation Infection 



Some of the research results presented in this entry were generated from the project funded by the National Heart, Lung, and Blood Institute (NHLBI) of the NIH, grant R44HL097485 and NIH grant P01HL573461. The authors are grateful for the contributions of all colleagues and collaborators in this research area of nanocoating technology for orthopedic implant application. We are also thankful for the thoughtful and constructive comments and suggestions of the reviewers, which have improved the presentation.

Conflict of interest: Dr. Hongmin Sun owns stocks in Nanova, Inc. This does not detract from an author’s objectivity in presentation of study results.


  1. 1.
    Davies D (2003) Understanding biofilm resistance to antibacterial agents. Nat Rev Drug Discov 2:114–122PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Donlan RM (2001) Biofilms and device-associated infections. Emerg Infect Dis 7:277–281PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Campoccia D, Montanaro L, Arciola CR (2006) The significance of infection related to orthopedic devices and issues of antibiotic resistance. Biomaterials 27(11):2331–2339CrossRefGoogle Scholar
  4. 4.
    Zaborowska M, Tillander J, Brånemark R, Hagberg L, Thomsen P, Trobos M (2017) Biofilm formation and antimicrobial susceptibility of staphylococci and enterococci from osteomyelitis associated with percutaneous orthopaedic implants. J Biomed Mater Res B Appl Biomater 105(8):2630–2640PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Li B, Webster TJ (2018) Bacteria antibiotic resistance: new challenges and opportunities for implant-associated orthopedic infections. J Orthop Res 36(1):22–32Google Scholar
  6. 6.
    Donlan RM, Costerton JW (2002) Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 15:167–193PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Darouiche RO (2004) Treatment of infections associated with surgical implants. N Engl J Med 350:1422–1429PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Steiner C, Andrews R, Barrett M, Weiss A (2012) HCUP Projections: Mobility/Orthopedic Procedures 2003 to 2012. HCUP Projections Report # 2012-03. 2012 Sep 20. U.S. Agency for Healthcare Research and Quality. Accessed 12 Apr 2019
  9. 9.
    Kurtz S, Ong K, Lau E, Mowat F, Halpern M (2007) Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am 89:780–785PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Kremers HM, Larson DR, Crowson CS, Kremers WK, Washington RE, Steiner CA, Jiranek WA, Berry DJ (2015) Prevalence of total hip and knee replacement in the United States. J Bone Joint Surg Am 97(17):1386–1397PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Antoci V Jr et al (2008) The inhibition of Staphylococcus epidermidis biofilm formation by vancomycin-modified titanium alloy and implications for the treatment of periprosthetic infection. Biomaterials 29:4684–4690PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Lucke M et al (2003) Gentamicin coating of metallic implants reduces implant-related osteomyelitis in rats. Bone 32:521–531PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Popat KC, Eltgroth M, LaTempa TJ, Grimes CA, Desai TA (2007) Decreased Staphylococcus epidermis adhesion and increased osteoblast functionality on antibiotic-loaded titania nanotubes. Biomaterials 28:4880–4888PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Sampath LA, Tambe SM, Modak SM (2001) In vitro and in vivo efficacy of catheters impregnated with antiseptics or antibiotics: evaluation of the risk of bacterial resistance to the antimicrobials in the catheters. Infect Control Hosp Epidemiol 22:640–646PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Tambe SM, Sampath L, Modak SM (2001) In vitro evaluation of the risk of developing bacterial resistance to antiseptics and antibiotics used in medical devices. J Antimicrob Chemother 47:589–598PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Jiang H, Manolache S, Wong ACL, Denes FS (2004) Plasma-enhanced deposition of silver nanoparticles onto polymer and metal surfaces for the generation of antimicrobial characteristics. J Appl Polym Sci 93:1411–1422CrossRefGoogle Scholar
  17. 17.
    Stobie N et al (2008) Prevention of Staphylococcus epidermidis biofilm formation using a low-temperature processed silver-doped phenyltriethoxysilane sol-gel coating. Biomaterials 29:963–969PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Zeng X, Xiong S, Zhuo S, Liu C, Miao J, Liu D, Wang H, Zhang Y, Zheng Z, Ting K, Wang C, Liu Y (2019) Nanosilver/poly (dl-lactic-co-glycolic acid) on titanium implant surfaces for the enhancement of antibacterial properties and osteoinductivity. Int J Nanomedicine 14:1849–1863PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Rai M, Yadav A, Gade A (2009) Silver nanoparticles as a new generation of antimicrobials. Biotechnol Adv 27:76–83CrossRefGoogle Scholar
  20. 20.
    Baveja JK et al (2004) Furanones as potential anti-bacterial coatings on biomaterials. Biomaterials 25:5003–5012PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Hume EB et al (2004) The control of Staphylococcus epidermidis biofilm formation and in vivo infection rates by covalently bound furanones. Biomaterials 25:5023–5030PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Klibanov AM (2007) Permanently microbicidal materials coatings. J Mater Chem 17:2479–2482CrossRefGoogle Scholar
  23. 23.
    Harris LG, Tosatti S, Wieland M, Textor M, Richards RG (2004) Staphylococcus aureus adhesion to titanium oxide surfaces coated with non-functionalized and peptide-functionalized poly(L-lysine)-grafted-poly(ethylene glycol) copolymers. Biomaterials 25:4135–4148PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Cheng G, Zhang Z, Chen S, Bryers JD, Jiang S (2007) Inhibition of bacterial adhesion and biofilm formation on zwitterionic surfaces. Biomaterials 28:4192–4199PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Privett BJ et al (2011) Antibacterial fluorinated silica colloid superhydrophobic surfaces. Langmuir 27:9597–9601PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Xu LC, Siedlecki CA (2012) Submicron-textured biomaterial surface reduces staphylococcal bacterial adhesion and biofilm formation. Acta Biomater 8:72–81PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Chien CY, Liu TY, Kuo WH, Wang MJ, Tsai WB (2013) Dopamine-assisted immobilization of hydroxyapatite nanoparticles and RGD peptides to improve the osteoconductivity of titanium. J Biomed Mater Res A 101:740–747PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Wang G, Zreiqat H (2010) Functional coatings or films for hard-tissue applications. Materials 3:3994–4050PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Wang Y, Liu X, Fan T, Tan Z, Zhou Z, He D (2017) In vitro evaluation of hydroxyapatite coatings with (002) crystallographic texture deposited by micro-plasma spraying. Mater Sci Eng C Mater Biol Appl 75:596–601PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Łukaszewska-Kuska M, Krawczyk P, Martyla A, Hędzelek W, Dorocka-Bobkowska B (2018) Hydroxyapatite coating on titanium endosseous implants for improved osseointegration: physical and chemical considerations. Adv Clin Exp Med 27(8):1055–1059PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Oosterbos CJ et al (2002) Osseointegration of hydroxyapatite-coated and noncoated Ti6Al4V implants in the presence of local infection: a comparative histomorphometrical study in rabbits. J Biomed Mater Res 60:339–347PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Vogely HC et al (2000) Effects of hydrosyapatite coating on Ti-6A1-4V implant-site infection in a rabbit tibial model. J Orthop Res 18:485–493PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Neoh KG, Hu X, Zheng D, Kang ET (2012) Balancing osteoblast functions and bacterial adhesion on functionalized titanium surfaces. Biomaterials 33:2813–2822PubMedCrossRefGoogle Scholar
  34. 34.
    Zhang F, Zhang Z, Zhu X, Kang ET, Neoh KG (2008) Silk-functionalized titanium surfaces for enhancing osteoblast functions and reducing bacterial adhesion. Biomaterials 29:4751–4759PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Maddikeri RR, Tosatti S, Schuler M, Chessari S, Textor M, Richards RG et al (2008) Reduced medical infection related bacterial strains adhesion on bioactive RGD modified titanium surfaces: a first step toward cell selective surfaces. J Biomed Mater Res A 84:425–435PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Subbiahdoss G et al (2010) Bacterial biofilm formation versus mammalian cell growth on titanium-based mono- and bi-functional coating. Eur Cell Mater 19:205–213PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Chua PH, Neoh KG, Kang ET, Wang W (2008) Surface functionalization of titanium with hyaluronic acid/chitosan polyelectrolyte multilayers and RGD for promoting osteoblast functions and inhibiting bacterial adhesion. Biomaterials 29:1412–1421PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Shi Z, Neoh KG, Kang ET, Poh C, Wang W (2008) Bacterial adhesion and osteoblast function on titanium with surface-grafted chitosan and immobilized RGD peptide. J Biomed Mater Res A 86:865–872PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Shi Z, Neoh KG, Kang ET, Poh C, Wang W (2009) Titanium with surface-grafted dextran and immobilized bone morphogenetic protein-2 for inhibition of bacterial adhesion and enhancement of osteoblast functions. Tissue Eng Part A 15:417–426PubMedCrossRefGoogle Scholar
  40. 40.
    Shi Z, Neoh KG, Kang ET, Poh CK, Wang W (2009) Surface functionalization of titanium with carboxymethyl chitosan and immobilized bone morphogenetic protein-2 for enhanced osseointegration. Biomacromolecules 10:1603–1611PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Hu X et al (2010) An in vitro assessment of titanium functionalized with polysaccharides conjugated with vascular endothelial growth factor for enhanced osseointegration and inhibition of bacterial adhesion. Biomaterials 31:8854–8863PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Ratner BD (1997) Plasma processing of polymers. In: d’Agostino R, Favia P, Fracassi F (eds) . Kluwer Academic Publishers, Dordrecht, The NetherlandsGoogle Scholar
  43. 43.
    Lerouge S, Major A, Girault-Lauriault PL, Raymond MA, Laplante P, Soulez G et al (2007) Nitrogen-rich coatings for promoting healing around stent-grafts after endovascular aneurysm repair. Biomaterials 28:1209–1217PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Chen M, Osaki S, Zamora PO, Potekhin M (2003) Effect of nitrogen and oxygen incorporated into TMSAA plasma coating on surface-bound heparin activity. J Appl Polym Sci 89:1875–1883CrossRefGoogle Scholar
  45. 45.
    Shen Y et al (2009) Investigation of surface endothelialization on biomedical nitinol (NiTi) alloy: effects of surface micropatterning combined with plasma nanocoatings. Acta Biomater 5:3593–3604PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Tang CJ et al (2010) A study on surface endothelialization of plasma coated intravascular stents. Surf Coat Technol 204:1487–1492CrossRefGoogle Scholar
  47. 47.
    Jones JE, Yu Q, M Chen M (2017) A chemical stability study of trimethylsilane plasma nanocoatings for coronary stents. J Biomater Sci Polym Ed 28(1):15–32PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Stallard CP, McDonnell KA, Onayemi OD, O'Gara JP, Dowling DP (2012) Evaluation of protein adsorption on atmospheric plasma deposited coatings exhibiting superhydrophilic to superhydrophobic properties. Biointerphases 7:31PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Ma Y et al (2012) Inhibition of Staphylococcus epidermidis biofilm by trimethylsilane plasma coating. Antimicrob Agents Chemother 56:5923–5937PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Yang Y, Kulangara K, Lam RT, Dharmawan R, Leong KW (2012) Effects of topographical and mechanical property alterations induced by oxygen plasma modification on stem cell behavior. ACS Nano 6:8591–8598PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Lee JT et al (2011) Cell culture medium as an alternative to conventional simulated body fluid. Acta Biomater 7:2615–2622PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Cassat JE, Lee CY, Smeltzer MS (2007) Investigation of biofilm formation in clinical isolates of Staphylococcus aureus. Methods Mol Biol 391:127–144PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Niska JA et al (2012) Monitoring bacterial burden, inflammation and bone damage longitudinally using optical and muCT imaging in an orthopaedic implant infection in mice. PLoS One 7:e47397PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Niska JA et al (2013) Vancomycin-rifampin combination therapy has enhanced efficacy against an experimental Staphylococcus aureus prosthetic joint infection. Antimicrob Agents Chemother 57:5080–5086PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Niska JA et al (2012) Daptomycin and tigecycline have broader effective dose ranges than vancomycin as prophylaxis against a Staphylococcus aureus surgical implant infection in mice. Antimicrob Agents Chemother 56:2590–2597PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Bernthal NM et al (2010) A mouse model of post-arthroplasty Staphylococcus aureus joint infection to evaluate in vivo the efficacy of antimicrobial implant coatings. PLoS One 5:e12580PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Xu Y et al (2015) Nanoscale plasma coating inhibits formation of Staphylococcus aureus biofilm. Antimicrob Agents Chemother 59(12):7308–7315PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Wu S et al (2011) Plasma-modified biomaterials for self-antimicrobial applications. ACS Appl Mater Interfaces 3:2851–2860PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Ma Y et al (2012) Novel inhibitors of Staphylococcus aureus virulence gene expression and biofilm formation. PLoS One 7:e47255PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Thevenot P et al (2008) Surface chemistry influence implant biocompatibility.Curr Top Med Chem 8(4): 270–280PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Cheung AL, Fischetti VA (1990) The role of fibrinogen in staphylococcal adherence to catheters in vitro. J Infect Dis 161:1177–1186PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Pei L, Flock JI (2001) Lack of fbe, the gene for a fibrinogen-binding protein from Staphylococcus epidermidis, reduces its adherence to fibrinogen coated surfaces. Microb Pathog 31:185–193PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Meng Chen
    • 1
    Email author
  • Hongmin Sun
    • 2
  • Hongjiao Ouyang
    • 3
  • John E. Jones
    • 1
  • Qingsong Yu
    • 4
  • Yuanxi Xu
    • 2
    • 5
  • Shankar Revu
    • 3
  1. 1.NanovaColumbiaUSA
  2. 2.School of MedicineUniversity of MissouriColumbiaUSA
  3. 3.College of DentistryTexas A&M UniversityDallasUSA
  4. 4.College of EngineeringUniversity of MissouriColumbiaUSA
  5. 5.Department of Clinical Development and RegistrationProtech Pharmaservices Corporation (PPC)ShanghaiChina

Personalised recommendations