Biomineral CaP Coating Reduces Inflammatory Behavior of PEEK Implants

Transcription

1 Biomineral CaP Coating Reduces Inflammatory Behavior of PEEK Implants L. Jongpaiboonkit 1, N. Caras 1, W. Murphy 2 1 Tissue Regeneration Systems, Inc, Plymouth, MI, United States 2 The University of Wisconsin, Madison, WI, United States 1

2 INTRODUCTION Prior research has suggested that the peri-inflammatory response around PEEK implants, also described as a halo effect, may be due to the stimulation of specific inflammatory cytokines that enhance fibrous tissue formation. 1 This halo effect has been observed as secondary to minimal osseointegration of PEEK at the adjacent vertebral endplate following a PEEK implant insertion Olivares-Navarrete R. Implant materials generate different peri-implant inflammatory factors: poly-ether-ether-ketone promotes fibrosis and microtextured titanium promotes osteogenic factors. Spine (Phila Pa 1976) Mar 15;40(6): doi: /BRS 2. Phan K., et al.. PEEK-Halo effect in interbody fusion. J Clin Neurosci 2016 Feb;24: doi: /j.jocn Epub 2015 Oct 21 2

3 INTRODUCTION (CONT.) The purpose of this study was to determine if a proprietary nanostructured Calcium Phosphate (CaP) coating on PEEK cylinders has the potential to reduce production of inflammatory mediators, and enhance production of anti-inflammatory mediators. This in vitro study examined the behavior of hmscs on PEEK and Carbon Fiber Reinforced (CF) PEEK substrates with and without the nanostructured CaP coating. Specifically, we examined 1) osteoblastic differentiation and 2) secretion of inflammatory interleukins. TECAPEEK CLASSIX WHITE ROD CF-PEEK: TECAPEEK CF30 BLACK ROD Uncoated Coated Uncoated Coated 3

4 METHODS A nanostructured CaP coating was applied to PEEK and CF-PEEK cylinders through a proprietary biomimetic precipitation process. Materials were subjected to surface pretreatments and subsequently incubated in a ph adjusted mineral solution. An incubation protocol was followed for 4 days resulting in a continuous, plate-like nanostructure coating that provides a high surface area favorable for cell attachment (right). SEM Image of CaP Coating. A proprietary aqueous solution process creates customizable nanoscale features to increase surface area for cell attachment. SEM of Uncoated PEEK SEM of Coated TECAPEEK CLASSIX WHITE ROD SEM of Coated CF-PEEK: TECAPEEK CF30 BLACK ROD 4

5 METHODS (CONT.) Human mesenchymal stem cells were cultured on tissue culture polystyrene, PEEK and CF-PEEK with and without CaP coating. Osteoblastic differentiation and specific inflammatory cytokines that enhance fibrous tissue formation were assessed after 5 days. Pro-Inflammatory Assays: Interleukin 6 Interleukin 8 Anti-Inflammatory Assays: Interleukin 10 Osteoblastic Differentiation: Proliferation Alkaline phosphatase 5

6 RESULTS The uncoated PEEK and CF-PEEK cylinders (circled in red) demonstrated relatively high levels of IL-6, and IL-8 (associated with chronic inflammation). The presence of the mineral coating on the PEEK and CF-PEEK (circled in green) eliminated the increases in proinflammatory cytokines. 6

7 RESULTS(cont.) In addition, the uncoated PEEK and CF-PEEK cylinders (circled in red) demonstrated lower levels of the anti-inflammatory cytokine, IL-10, and the presence of the mineral coating (circled in green) showed increases in this anti-inflammatory cytokine for both types of coated PEEK. 7

8 RESULTS (CONT.) Lastly, the coated PEEK cylinders promoted enhanced osteoblastic differentiation in comparison to uncoated PEEK cylinders, as demonstrated through increased proliferation rates and alkaline phosphatase. 8

9 CONCLUSION These results suggest that this proprietary CaP coating could reduce the production of specific inflammatory cytokines that enhance fibrous tissue formation, while enhancing osteoblastic differentiation on PEEK implants. This biologic response to coated PEEK and CF-PEEK potentially translates to a reduced potential for the halo effect. The osteostimulatory characteristics demonstrated by this coating are likely attributable to 1) the release of soluble calcium and phosphate ions, which can stimulate osteoblasts and osteoblast precursors, and 2) nanoscale surface topography, which has been implicated as a mechanism to promote osteoblast proliferation and osteoblast precursor differentiation. In addition, calcium phosphate materials with a nano-structured topography have been shown to modulate macrophage activation toward reducing the severity of inflammation, while a larger microscale topography triggered an increased activation response Mestres, G., Espanol, M., Xia, W., Persson, C., Ginebra, M.P., Ott, M.K. Inflammatory Response to Nano- and Microstructured Hydroxyapatite. PLOS ONE DOI: (2015). 9

10 DISCLOSURES Declaration of Prior Submission or Presentation: None. Disclosure of Conflict of Interest: Author disclosure: LJ and NC: Dr. Jongpaiboonkit and Mr. Caras are employees of Tissue Regeneration Systems, Inc. WM: Dr. Murphy is co-founder and equity holder in Tissue Regeneration Systems, Inc. and Stem Pharm, Inc. Institutional Review Board (IRB) Disclosure: N/A. Animal Care and Use (IACUC) Disclosure: N/A. FDA Disclosure: N/A. 10