Antimicrobial peptides on calcium phosphate-coated titanium for the prevention of implant-associated infections

Mehdi Kazemzadeh-Narbat, Jason Kindrachuk, Ke Duan, Håvard Jenssen, Robert E.W. Hancock, Rizhi Wang

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Prevention of implant-associated infections has been one of the main challenges in orthopaedic surgery. This challenge is further complicated by the concern over the development of antibiotic resistance as a result of using traditional antibiotics for infection prophylaxis. The objective of this study was to develop a technique that enables the loading and local delivery of a unique group of cationic antimicrobial peptides (AMP) through implant surfaces. A thin layer of micro-porous calcium phosphate (CaP) coating was processed by electrolytic deposition onto the surface of titanium as the drug carrier. The broad spectrum AMP Tet213 (KRWWKWWRRC) was selected and loaded onto the CaP coating. SEM, XRD and FTIR analyses confirmed the CaP coating to be micro-porous octacalcium phosphate. By using a luminescence spectrometer technique, it was demonstrated that a 7 mm thick porous CaP coating could load up to 9 mg of AMP/cm2 using a simple soaking technique. The drug-loaded CaP coating (CaP-Tet213) was not cytotoxic for MG-63 osteoblast-like cells. The CaP-Tet213 implants had antimicrobial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria with 106-fold reductions of both bacterial strains within 30 min as assessed by measuring
    colony-forming units (CFU). Repeated CFU assays on the same CaP-Tet213 specimen demonstrated retention of antimicrobial activity by the CaP-Tet213 surfaces through four test cycles. The susceptibility of bacteria to the CaP-Tet213 surfaces was also evaluated by assessing the inhibition of luminescence of
    P. aeruginosa containing a luxCDABE cassette at 4 h and 24 h with w92% and w77% inhibition of luminescence, respectively. It was demonstrated that CaP-Tet213 was a more efficient antimicrobial coating than CaP-MX226, CaP-hLF1-11 or CaP-tobramycin following incubation of CaP implants with equimolar
    concentrations of Tet213, the commercially developed antimicrobial peptide MX-226, hLF1-11 or tobramycin. A device coated with CaP-Tet213 could be a potential solution for the prevention of the periimplant infection in orthopaedics.
    OriginalsprogEngelsk
    TidsskriftBiomaterials
    Vol/bind31
    Udgave nummer36
    Sider (fra-til)9519-9526
    ISSN0142-9612
    DOI
    StatusUdgivet - 2010

    Emneord

      Citer dette

      Kazemzadeh-Narbat, Mehdi ; Kindrachuk, Jason ; Duan, Ke ; Jenssen, Håvard ; Hancock, Robert E.W. ; Wang, Rizhi. / Antimicrobial peptides on calcium phosphate-coated titanium for the prevention of implant-associated infections. I: Biomaterials. 2010 ; Bind 31, Nr. 36. s. 9519-9526.
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      title = "Antimicrobial peptides on calcium phosphate-coated titanium for the prevention of implant-associated infections",
      abstract = "Prevention of implant-associated infections has been one of the main challenges in orthopaedic surgery. This challenge is further complicated by the concern over the development of antibiotic resistance as a result of using traditional antibiotics for infection prophylaxis. The objective of this study was to develop a technique that enables the loading and local delivery of a unique group of cationic antimicrobial peptides (AMP) through implant surfaces. A thin layer of micro-porous calcium phosphate (CaP) coating was processed by electrolytic deposition onto the surface of titanium as the drug carrier. The broad spectrum AMP Tet213 (KRWWKWWRRC) was selected and loaded onto the CaP coating. SEM, XRD and FTIR analyses confirmed the CaP coating to be micro-porous octacalcium phosphate. By using a luminescence spectrometer technique, it was demonstrated that a 7 mm thick porous CaP coating could load up to 9 mg of AMP/cm2 using a simple soaking technique. The drug-loaded CaP coating (CaP-Tet213) was not cytotoxic for MG-63 osteoblast-like cells. The CaP-Tet213 implants had antimicrobial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria with 106-fold reductions of both bacterial strains within 30 min as assessed by measuring colony-forming units (CFU). Repeated CFU assays on the same CaP-Tet213 specimen demonstrated retention of antimicrobial activity by the CaP-Tet213 surfaces through four test cycles. The susceptibility of bacteria to the CaP-Tet213 surfaces was also evaluated by assessing the inhibition of luminescence of P. aeruginosa containing a luxCDABE cassette at 4 h and 24 h with w92{\%} and w77{\%} inhibition of luminescence, respectively. It was demonstrated that CaP-Tet213 was a more efficient antimicrobial coating than CaP-MX226, CaP-hLF1-11 or CaP-tobramycin following incubation of CaP implants with equimolar concentrations of Tet213, the commercially developed antimicrobial peptide MX-226, hLF1-11 or tobramycin. A device coated with CaP-Tet213 could be a potential solution for the prevention of the periimplant infection in orthopaedics.",
      keywords = "Calcium phosphate coating, Electrolytic deposition, Antimicrobial peptide, Titanium, Infection, Orthopaedic implants",
      author = "Mehdi Kazemzadeh-Narbat and Jason Kindrachuk and Ke Duan and H{\aa}vard Jenssen and Hancock, {Robert E.W.} and Rizhi Wang",
      year = "2010",
      doi = "10.1016/j.biomaterials.2010.08.035",
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      Antimicrobial peptides on calcium phosphate-coated titanium for the prevention of implant-associated infections. / Kazemzadeh-Narbat, Mehdi ; Kindrachuk, Jason ; Duan, Ke; Jenssen, Håvard; Hancock, Robert E.W. ; Wang, Rizhi.

      I: Biomaterials, Bind 31, Nr. 36, 2010, s. 9519-9526.

      Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

      TY - JOUR

      T1 - Antimicrobial peptides on calcium phosphate-coated titanium for the prevention of implant-associated infections

      AU - Kazemzadeh-Narbat, Mehdi

      AU - Kindrachuk, Jason

      AU - Duan, Ke

      AU - Jenssen, Håvard

      AU - Hancock, Robert E.W.

      AU - Wang, Rizhi

      PY - 2010

      Y1 - 2010

      N2 - Prevention of implant-associated infections has been one of the main challenges in orthopaedic surgery. This challenge is further complicated by the concern over the development of antibiotic resistance as a result of using traditional antibiotics for infection prophylaxis. The objective of this study was to develop a technique that enables the loading and local delivery of a unique group of cationic antimicrobial peptides (AMP) through implant surfaces. A thin layer of micro-porous calcium phosphate (CaP) coating was processed by electrolytic deposition onto the surface of titanium as the drug carrier. The broad spectrum AMP Tet213 (KRWWKWWRRC) was selected and loaded onto the CaP coating. SEM, XRD and FTIR analyses confirmed the CaP coating to be micro-porous octacalcium phosphate. By using a luminescence spectrometer technique, it was demonstrated that a 7 mm thick porous CaP coating could load up to 9 mg of AMP/cm2 using a simple soaking technique. The drug-loaded CaP coating (CaP-Tet213) was not cytotoxic for MG-63 osteoblast-like cells. The CaP-Tet213 implants had antimicrobial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria with 106-fold reductions of both bacterial strains within 30 min as assessed by measuring colony-forming units (CFU). Repeated CFU assays on the same CaP-Tet213 specimen demonstrated retention of antimicrobial activity by the CaP-Tet213 surfaces through four test cycles. The susceptibility of bacteria to the CaP-Tet213 surfaces was also evaluated by assessing the inhibition of luminescence of P. aeruginosa containing a luxCDABE cassette at 4 h and 24 h with w92% and w77% inhibition of luminescence, respectively. It was demonstrated that CaP-Tet213 was a more efficient antimicrobial coating than CaP-MX226, CaP-hLF1-11 or CaP-tobramycin following incubation of CaP implants with equimolar concentrations of Tet213, the commercially developed antimicrobial peptide MX-226, hLF1-11 or tobramycin. A device coated with CaP-Tet213 could be a potential solution for the prevention of the periimplant infection in orthopaedics.

      AB - Prevention of implant-associated infections has been one of the main challenges in orthopaedic surgery. This challenge is further complicated by the concern over the development of antibiotic resistance as a result of using traditional antibiotics for infection prophylaxis. The objective of this study was to develop a technique that enables the loading and local delivery of a unique group of cationic antimicrobial peptides (AMP) through implant surfaces. A thin layer of micro-porous calcium phosphate (CaP) coating was processed by electrolytic deposition onto the surface of titanium as the drug carrier. The broad spectrum AMP Tet213 (KRWWKWWRRC) was selected and loaded onto the CaP coating. SEM, XRD and FTIR analyses confirmed the CaP coating to be micro-porous octacalcium phosphate. By using a luminescence spectrometer technique, it was demonstrated that a 7 mm thick porous CaP coating could load up to 9 mg of AMP/cm2 using a simple soaking technique. The drug-loaded CaP coating (CaP-Tet213) was not cytotoxic for MG-63 osteoblast-like cells. The CaP-Tet213 implants had antimicrobial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa) bacteria with 106-fold reductions of both bacterial strains within 30 min as assessed by measuring colony-forming units (CFU). Repeated CFU assays on the same CaP-Tet213 specimen demonstrated retention of antimicrobial activity by the CaP-Tet213 surfaces through four test cycles. The susceptibility of bacteria to the CaP-Tet213 surfaces was also evaluated by assessing the inhibition of luminescence of P. aeruginosa containing a luxCDABE cassette at 4 h and 24 h with w92% and w77% inhibition of luminescence, respectively. It was demonstrated that CaP-Tet213 was a more efficient antimicrobial coating than CaP-MX226, CaP-hLF1-11 or CaP-tobramycin following incubation of CaP implants with equimolar concentrations of Tet213, the commercially developed antimicrobial peptide MX-226, hLF1-11 or tobramycin. A device coated with CaP-Tet213 could be a potential solution for the prevention of the periimplant infection in orthopaedics.

      KW - Calcium phosphate coating

      KW - Electrolytic deposition

      KW - Antimicrobial peptide

      KW - Titanium

      KW - Infection

      KW - Orthopaedic implants

      U2 - 10.1016/j.biomaterials.2010.08.035

      DO - 10.1016/j.biomaterials.2010.08.035

      M3 - Journal article

      VL - 31

      SP - 9519

      EP - 9526

      JO - Biomaterials

      JF - Biomaterials

      SN - 0142-9612

      IS - 36

      ER -