Material modifications enhancing the antibacterial properties of two biodegradable poly(3-hydroxybutyrate) implants

The aim of this study was to evaluate the antimicrobial efficacy of adding a gentamicin palmitate (GP) coating and zirconium dioxide (ZrO2) to biodegradable poly(3-hydroxybutyrate) (PHB) to reduce biofilm formation. Cylindrical pins with and without a coating were incubated in Müller-Hinton broth inoculated with 2 × 105 colony-forming units (CFU) ml-1 of Staphylococcus aureus for 2 d or 7 d, then sonicated to disrupt biofilms. Pure PHB (PHB + GP) and PHB pins with ZrO2 added (PHBzr + GP) were coated with GP and compared with PHB pins lacking a coating (PHB). Cells (CFU) were counted to quantify the number of bacteria in the biofilm and a cell proliferation assay was employed to evaluate metabolic activity, and scanning electron microscopy (SEM) was performed to visualize the structure of the biofilm. After 2 d of incubation there were significantly more cells in biofilms on PHB pins than PHB + GP and PHBzr + GP pins (p < 0.0001), and cells in the sonication fluid obtained from GP-coated pins exhibited significantly lower metabolic activity than cells from uncoated PHB pins (p < 0.0001). After 7 d of incubation metabolic activity was lowest for PHBzr + GP, with significant differences between PHB and PHBzr + GP (p = 0.001). SEM revealed more cells attached to the surface, and more structured biofilms, on pins without a coating. Coating pins with GP significantly reduced early biofilm formation on PHB implants. This could lower the potential risk of surgical site infections when using PHB implants. Addition of ZrO2 might further enhance the antibacterial properties. Such modification of the implant material should therefore be considered when developing new biodegradable PHB implants.

[1]  J. John The treatment of resistant staphylococcal infections , 2020, F1000Research.

[2]  E. Pellizzer,et al.  Influence of addition of zirconia on PMMA: A systematic review. , 2020, Materials science & engineering. C, Materials for biological applications.

[3]  Ž. Knez,et al.  Poly(3-hydroxybutyrate): Promising biomaterial for bone tissue engineering , 2019, Acta pharmaceutica.

[4]  Lakshmi Kalyani Ruddaraju,et al.  A review on anti-bacterials to combat resistance: From ancient era of plants and metals to present and future perspectives of green nano technological combinations , 2019, Asian journal of pharmaceutical sciences.

[5]  M. Nogler,et al.  Increased Staphylococcus aureus biofilm formation on biodegradable PHB-implants compared to conventional orthopedic implants: an in vitro analysis. , 2020, Journal of orthopaedic trauma.

[6]  J. Geurts,et al.  Antibiotic-Loaded Polymethylmethacrylate Beads and Spacers in Treatment of Orthopedic Infections and the Role of Biofilm Formation , 2019, Front. Microbiol..

[7]  A. Pugazhendhi,et al.  Synthesis and characterization of ZrO2 nanoparticles-antimicrobial activity and their prospective role in dental care. , 2017, Microbial pathogenesis.

[8]  M. Gad,et al.  Inhibitory effect of zirconium oxide nanoparticles on Candida albicans adhesion to repaired polymethyl methacrylate denture bases and interim removable prostheses: a new approach for denture stomatitis prevention , 2017, International journal of nanomedicine.

[9]  C. Meyer,et al.  Antibiotic Elution from Hip and Knee Acrylic Bone Cement Spacers: A Systematic Review , 2017, BioMed research international.

[10]  V. Alt Antimicrobial coated implants in trauma and orthopaedics-A clinical review and risk-benefit analysis. , 2017, Injury.

[11]  O. Braissant,et al.  In Vitro Biofilm Formation on Titanium and Zirconia Implant Surfaces , 2017, Journal of periodontology.

[12]  A. Winkel,et al.  Quantifying implant-associated biofilms: Comparison of microscopic, microbiologic and biochemical methods. , 2016, Journal of microbiological methods.

[13]  J. L. Drury,et al.  Zirconia in biomedical applications , 2016, Expert review of medical devices.

[14]  L. Frommelt,et al.  Lyophilized allogeneic bone tissue as an antibiotic carrier , 2016, Cell and Tissue Banking.

[15]  S. Stanzl-Tschegg,et al.  Adhesive strength of bone-implant interfaces and in-vivo degradation of PHB composites for load-bearing applications. , 2016, Journal of the mechanical behavior of biomedical materials.

[16]  J. Monllau,et al.  Use of antibiotic-loaded cement in total knee arthroplasty. , 2015, World journal of orthopedics.

[17]  D. Wozniak,et al.  Prevention and treatment of Staphylococcus aureus biofilms , 2015, Expert review of anti-infective therapy.

[18]  Marco A. Velasco,et al.  Design, Materials, and Mechanobiology of Biodegradable Scaffolds for Bone Tissue Engineering , 2015, BioMed research international.

[19]  S. Fuchs-Winkelmann,et al.  Coating with a novel gentamicinpalmitate formulation prevents implant-associated osteomyelitis induced by methicillin-susceptible Staphylococcus aureus in a rat model , 2015, International Orthopaedics.

[20]  M. Boguń,et al.  Gentamicin release from biodegradable poly-l-lactide based composites for novel intramedullary nails. , 2014, Materials science & engineering. C, Materials for biological applications.

[21]  Sumio Shinoda,et al.  Current Perspectives on Viable but Non-Culturable (VBNC) Pathogenic Bacteria , 2014, Front. Public Health.

[22]  Fernando J. Monteiro,et al.  Infection of orthopedic implants with emphasis on bacterial adhesion process and techniques used in studying bacterial-material interactions , 2012, Biomatter.

[23]  R. Pasricha,et al.  Antimicrobial activity of zirconia (ZrO2) nanoparticles and zirconium complexes. , 2012, Journal of nanoscience and nanotechnology.

[24]  Carla Renata Arciola,et al.  Biofilm formation in Staphylococcus implant infections. A review of molecular mechanisms and implications for biofilm-resistant materials. , 2012, Biomaterials.

[25]  S. Stanzl-Tschegg,et al.  PHB, crystalline and amorphous magnesium alloys: promising candidates for bioresorbable osteosynthesis implants? , 2012, Materials science & engineering. C, Materials for biological applications.

[26]  D. Coraça-Huber,et al.  The use of vancomycin-loaded poly-l-lactic acid and poly-ethylene oxide microspheres for bone repair: An in vivo study , 2012, Clinics.

[27]  M. Nogler,et al.  Staphylococcus aureus biofilm formation and antibiotic susceptibility tests on polystyrene and metal surfaces , 2012, Journal of applied microbiology.

[28]  A. Weinberg,et al.  Antimicrobial activity of gentamicin palmitate against high concentrations of Staphylococcus aureus , 2011, Journal of materials science. Materials in medicine.

[29]  R. P. John,et al.  An overview of the recent developments in polylactide (PLA) research. , 2010, Bioresource technology.

[30]  J. Kelm,et al.  Elution of gentamicin and vancomycin from polymethylmethacrylate beads and hip spacers in vivo , 2009, Acta orthopaedica.

[31]  U. Holzgrabe,et al.  Evaluation of the stability of gentamicin in different antibiotic carriers using a validated MEKC method. , 2008, Journal of pharmaceutical and biomedical analysis.

[32]  J. Calhoun,et al.  Osteomyelitis and the role of biofilms in chronic infection. , 2008, FEMS immunology and medical microbiology.

[33]  M. Schnabelrauch,et al.  Resorbable Antibiotic Coatings for Bone Substitutes and Implantable Devices , 2005 .

[34]  A. Hanssen,et al.  Practical applications of antibiotic-loaded bone cement for treatment of infected joint replacements. , 2004, Clinical orthopaedics and related research.

[35]  J. Planell,et al.  Mechanical performance of acrylic bone cements containing different radiopacifying agents. , 2002, Biomaterials.

[36]  J. Costerton,et al.  Biofilms: Survival Mechanisms of Clinically Relevant Microorganisms , 2002, Clinical Microbiology Reviews.

[37]  P. Chang Polymer implant materials with improved X-ray opacity and biocompatibility. , 1981, Biomaterials.

[38]  H. Buchholz,et al.  [Depot effects of various antibiotics mixed with Palacos resins]. , 1970, Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen.