Antibacterial properties of PEKK for orthopedic applications
Authors: Mian Wang
Garima Bhardwaj
Thomas J Webster
Journal: International Journal of Nanomedicine (2017)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: PEEK; PEKK; bacteria; infection; orthopedic.
Affiliations: Department of Chemical Engineering, Northeastern University, Boston, MA, USA., Wenzhou Institute of Biomaterials and Engineering, Wenzhou Medical University, Wenzhou, People's Republic of China.

Abstract:  Orthopedic implant infections have been steadily increasing while, at the same time, antibiotics developed to kill such bacteria have proven less and less effective with every passing day. It is clear that new approaches that do not rely on the use of antibiotics are needed to decrease medical device infections. Inspired by cicada wing surface topographical features, nanostructured surfaces represent a new approach for imposing antibacterial properties to biomaterials without using drugs. Moreover, new chemistries with altered surface energetics may decrease bacterial attachment and growth. In this study, a nanostructured surface was fabricated on poly-ether-ketone-ketone (PEKK), a new orthopedic implant chemistry, comprised of nanopillars with random interpillar spacing. Specifically, after 5 days, when compared to the orthopedic industry standard poly-ether-ether-ketone (PEEK), more than 37% less Staphylococcus epidermidis were found on the PEKK surface. Pseudomonas aeruginosa attachment and growth also decreased 28% after one day of culture, with around a 50% decrease after 5 days of culture when compared to PEEK. Such decreases in bacteria function were achieved without using antibiotics. In this manner, this study demonstrated for the first time, the promise that nanostructured PEKK has for numerous anti-infection orthopedic implant applications. 

Retracted: No

PubPeer comments:
 Figures 6 and 7 appear to have a repeated image, described differently. Marked in red. *** ![file] , 
 Thank you for pointing this out and we are currently investigating this - Tom Webster , 
 Seemingly no action after 8 months. However, this press release was made today: [Antibacterial Properties of OsteoFabu00ae PEKK Implants Defined in New Research, Outperforming PEEK and Titanium](http: www.prweb.com releases antibacterial_properties_of_osteofab_pekk_implants_defined_in_new_research_outperforming_peek_and_titanium prweb17546532.htm) SOUTH WINDSOR, CONN. (PRWEB) NOVEMBER 18, 2020 Oxford Performance Materials, Inc. (OPM), an industry leader in advanced materials science and high performance additive manufacturing (HPAMu00ae), today announced additional results of an ongoing scientific study analyzing the antibacterial properties of 3D printed PEKK (poly-ether-ketone-ketone). These new results definitively establish a mechanism of action for how 3D printed PEKK exhibits inherent antibacterial characteristics, further confirming PEKKu2019s role in combatting implant infections. In a continued partnership with Dr. Thomas Webster of Northeastern University, this research builds upon a September 2017 study(1) where samples produced by OPMu2019s proprietary OsteoFabu00ae process u201cdemonstrated for the first time the promise that nanostructured PEKK has for numerous anti-infection orthopedic implant applications.u201d In a second set of experiments conducted by Dr. Webster in December 2019, it was determined that 3D printed PEKK demonstrated significant reductions for all bacteria colonization(2) when measured via colony forming units, crystal violet staining, and live dead assays. This was true for all tested bacteria strains, which included S. epidermidis, P. aeruginosa, and MRSA, and all tested materials, as 3D printed PEKK significantly outperformed commercially available titanium and PEEK controls. This study was important for two primary reasons: it confirmed the results seen in the 2017 study(1) in the presence of titanium and PEEK controls and it raised the question of why PEKK is superior in this aspect, hinting that 3D printed PEKK may have a biologically optimal surface energy in the context of bacterial aversion. In April of 2020, a follow-up study was conducted to determine the mechanisms of the antibacterial properties of 3D printed PEKK after 24 hours of culture, specifically examining protein adsorption and correlating that adsorption to bacteria response. Based on the test results(2), 3D printed PEKK exhibited a surface energy (35.7 mN m) that was much closer to proteins lubricin (40 mN m), mucin (42-46 mN m), and casein (48 mN m), which are all proteins known to reduce bacteria attachment and colonization naturally in vivo. When compared to the surface energies of PEEK (16.3 mN m) and titanium (62.5 mN m), it was evident 3D printed PEKK is optimal in terms of similarity to these naturally occurring proteins. As expected, the experiment showed greater protein adsorption of lubricin, mucin, and casein on PEKK in comparison to PEEK and titanium controls. This greater protein adsorption was then correlated to greater bacteria inhibition of 3D printed PEKK compared to commercially available PEEK and titanium. For this portion of the study, samples were coated with lubricin, mucin, and casein, and bacteria attachment was characterized using colony forming unit counts, crystal violet staining, and live dead assays. All results correlated the increased protein adsorption to decreased bacteria colonization for S. epidermidis, P. aeruginosa, and MRSA, again compared to PEEK and titanium controls. This finding is extremely important as it provides objective evidence explaining why OPMu2019s 3D printed PEKK exhibits inherent antibacterial effects. u201cWe have been continually impressed with the strong bacteria resistance and pro-bone cell responses of OPMu2019s PEKK samples,u201d said Dr. Webster. u201cAll resulting from optimal surface properties without resorting to the use of antibiotics or the release of growth factors, as our studies have shown.u201d Equally significant are the implications of lubricin adsorption onto 3D printed PEKK, in terms of future joint and cartilage applications of the OsteoFab technology platform. Lubricin is a naturally occurring protein that is secreted in synovial joints; it coats surrounding cartilage and contributes to the overall integrity of the joint. With demonstrated adhesion to 3D printed PEKK, new devices could provide even more benefits in an increasing number of orthopedic applications. The antibacterial attributes of 3D printed PEKK are significant since they address a key area of growing concern in medicine u2013 orthopedic implant infections. 3D printed PEKKu2019s antibacterial properties, as detailed in this new study, will provide another important layer of differentiation for the performance of OsteoFab medical devices in the marketplace. Results from these experiments will be available in a forthcoming publication. About Oxford Performance Materials, Inc. Oxford Performance Materials, Inc. was founded in 2000 to exploit and commercialize the worldu2019s highest performing thermoplastic, PEKK (poly-ether-ketone-ketone). OPMu2019s Materials business has developed a range of proprietary, patented technologies for the synthesis and modification of a range of PAEK polymers that are sold under its OXPEKKu00ae brand for biomedical and industrial applications. The Company is a pioneer in 3D printing. OPM Biomedicalu2019s OsteoFabu00ae technology is in commercial production in numerous orthopedic implant applications, including cranial, facial, spinal, and sports medicine devices. OPM is the first and only company to receive FDA 510(k) clearance to manufacture 3D printed, patient-specific polymeric implants, and the company has six 510(k) clearances in its portfolio. OPM Industrial produces 3D printed OXFABu00ae production parts for highly demanding applications in the energy, transportation, and semiconductor markets. OXFABu00ae structures offer significant weight, cost, and time-to-market reductions that are defined in a set of specified performance attributes in the exhaustive OPM B-Basis database, developed in conjunction with NASA. For more information, please visit: http: www.oxfordpm.com References 1. u201cAntibacterial Properties of PEKK for Orthopedic Applications,u201d International Journal of Nanomedicine, Dovepress 15-Sep-2017, Mian Wang, Garima Bhardwaj (Department of Chemical Engineering, Northeastern University, Boston MA) and Thomas J. Webster (Department of Chemical Engineering, Northeastern University, Boston MA and Wenzhou Institute of Biomaterials and Engineering, Wenzhou Medical University, Wenzhou, China). The full study by Mian Wang, et al. may be viewed at https: www.ncbi.nlm.nih.gov pmc articles PMC5592909 2. https: oxfordpm.com uploads files OPM-T._Webster_AM_Med_Summit_19Oct2020_website.pdf?v=1605303394194 Perhaps Dr. Webster can clarify whether his is compensated or has a conflict of interest with Oxford, given that the presentation from reference 2 is on the company s own PowerPoint template (samples slides shown below). The conflict of interest disclosure on this particular paper does not mention Oxford. Also worth noting is that Dr. Webster is EiC of this journal, International Journal of Nanomedicine. ![file] ![file] Update: In this paper, u201cThe authors would like to thank RTI Surgical for funding this study.u201d Then note: [Oxford Performance Materialsu2019 Partner RTI Surgical Wins 2018 Orthopedics This Week Spine Technology Award] , 
 An image in Figure 6 appears to have a repeated region. *** ![file] , 
 Appears to be a similar issue in Figure 7. Perhaps these apparent modifications were done when relabeling the figures. *** ![file] , 
 May 31, 2021 The authors have advised Figure 7 on page 6475 is incorrect. The authors inadvertently included a duplicate image for the live dead Staphylococcus epidermidis and Pseudomonas aeruginosa PEEK samples shown in Figures 6 and 7, respectively. The correct Figure 7 is shown below. ![file] , 
 July 13, 2022  An error during the preparation of Figure 6 for publishing led to the inadvertent creation of duplicate features in the PEEK image and alterations in the PEKK image on page 6475. The journal wishes to apologise for these errors. The correct version of Figure 6 is shown in Download Article. ![file] ,