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Implant materials generate different peri-implant inflammatory factors: poly-ether-ether-ketone promotes fibrosis and microtextured titanium promotes osteogenic factors.

Olivares-Navarrete R, Hyzy SL, Slosar PJ, Schneider JM, Schwartz Z, Boyan BD - Spine (2015)

Bottom Line: Cells grown on mmnTiAlV had reduced levels of proinflammatory interleukins.Cells on PEEK had higher mRNAs for factors strongly associated with cell death/apoptosis, whereas cells on mmnTiAlV exhibited reduced cytokine factor levels.All results were significant (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: *Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA †SpineCare Medical Group, San Francisco Spine Institute, San Francisco, CA ‡Titan Spine, LLC, Mequon, WI §Department of Periodontics, The University of Texas Health Science Center at San Antonio, San Antonio, TX; and ¶Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA.

ABSTRACT

Study design: An in vitro study examining factors produced by human mesenchymal stem cells on spine implant materials.

Objective: The aim of this study was to examine whether the inflammatory microenvironment generated by cells on titanium-aluminum-vanadium (Ti-alloy, TiAlV) surfaces is affected by surface microtexture and whether it differs from that generated on poly-ether-ether-ketone (PEEK).

Summary of background data: Histologically, implants fabricated from PEEK have a fibrous connective tissue surface interface whereas Ti-alloy implants demonstrate close approximation with surrounding bone. Ti-alloy surfaces with complex micron/submicron scale roughness promote osteoblastic differentiation and foster a specific cellular environment that favors bone formation whereas PEEK favors fibrous tissue formation.

Methods: Human mesenchymal stem cells were cultured on tissue culture polystyrene, PEEK, smooth TiAlV, or macro-/micro-/nano-textured rough TiAlV (mmnTiAlV) disks. Osteoblastic differentiation and secreted inflammatory interleukins were assessed after 7 days. Fold changes in mRNAs for inflammation, necrosis, DNA damage, or apoptosis with respect to tissue culture polystyrene were measured by low-density polymerase chain reaction array. Data were analyzed by analysis of variance, followed by Bonferroni's correction of Student's t-test.

Results: Cells on PEEK upregulated mRNAs for chemokine ligand-2, interleukin (IL) 1β, IL6, IL8, and tumor necrosis factor. Cells grown on the mmnTiAlV had an 8-fold reduction in mRNAs for toll-like receptor-4. Cells grown on mmnTiAlV had reduced levels of proinflammatory interleukins. Cells on PEEK had higher mRNAs for factors strongly associated with cell death/apoptosis, whereas cells on mmnTiAlV exhibited reduced cytokine factor levels. All results were significant (P < 0.05).

Conclusion: These results suggest that fibrous tissue around PEEK implants may be due to several factors: reduced osteoblastic differentiation of progenitor cells and production of an inflammatory environment that favors cell death via apoptosis and necrosis. Ti alloy surfaces with complex macro/micro/nanoscale roughness promote osteoblastic differentiation and foster a specific cellular environment that favors bone formation.

Level of evidence: N/A.

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Related in: MedlinePlus

DNA content (A), alkaline phosphatase–specific activity (B), and osteocalcin production (C) in mesenchymal stem cells cultured on TCPS, PEEK, sTiAlV, or mmnTiAlV. *P < 0.05 versus TCPS; †P < 0.05 versus PEEK; ‡P < 0.05 versus sTiAlV. TCPS indicates tissue culture polystyrene; PEEK, poly-ether-ether-ketone; sTiAlV, smooth titanium-aluminum-vanadium alloy; mmnTiAlV, macro-/micro-/nano-textured rough TiAlV.
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Figure 2: DNA content (A), alkaline phosphatase–specific activity (B), and osteocalcin production (C) in mesenchymal stem cells cultured on TCPS, PEEK, sTiAlV, or mmnTiAlV. *P < 0.05 versus TCPS; †P < 0.05 versus PEEK; ‡P < 0.05 versus sTiAlV. TCPS indicates tissue culture polystyrene; PEEK, poly-ether-ether-ketone; sTiAlV, smooth titanium-aluminum-vanadium alloy; mmnTiAlV, macro-/micro-/nano-textured rough TiAlV.

Mentions: DNA content was significantly lower in cultures on PEEK and mmnTiAlV, but not different on sTiAlV, in comparison with TCPS (Figure 2A). Alkaline phosphatase activity was the same in MSCs cultured on TCPS or PEEK (Figure 2B) and was significantly higher on TiAlV surfaces in comparison with both TCPS and PEEK. Levels were significantly higher on mmnTiAlV than activity on the sTiAlV surface. Likewise, osteocalcin production was increased only on the Ti alloy surfaces, with the effect being greater on mmnTiAlV (Figure 2C).


Implant materials generate different peri-implant inflammatory factors: poly-ether-ether-ketone promotes fibrosis and microtextured titanium promotes osteogenic factors.

Olivares-Navarrete R, Hyzy SL, Slosar PJ, Schneider JM, Schwartz Z, Boyan BD - Spine (2015)

DNA content (A), alkaline phosphatase–specific activity (B), and osteocalcin production (C) in mesenchymal stem cells cultured on TCPS, PEEK, sTiAlV, or mmnTiAlV. *P < 0.05 versus TCPS; †P < 0.05 versus PEEK; ‡P < 0.05 versus sTiAlV. TCPS indicates tissue culture polystyrene; PEEK, poly-ether-ether-ketone; sTiAlV, smooth titanium-aluminum-vanadium alloy; mmnTiAlV, macro-/micro-/nano-textured rough TiAlV.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4363266&req=5

Figure 2: DNA content (A), alkaline phosphatase–specific activity (B), and osteocalcin production (C) in mesenchymal stem cells cultured on TCPS, PEEK, sTiAlV, or mmnTiAlV. *P < 0.05 versus TCPS; †P < 0.05 versus PEEK; ‡P < 0.05 versus sTiAlV. TCPS indicates tissue culture polystyrene; PEEK, poly-ether-ether-ketone; sTiAlV, smooth titanium-aluminum-vanadium alloy; mmnTiAlV, macro-/micro-/nano-textured rough TiAlV.
Mentions: DNA content was significantly lower in cultures on PEEK and mmnTiAlV, but not different on sTiAlV, in comparison with TCPS (Figure 2A). Alkaline phosphatase activity was the same in MSCs cultured on TCPS or PEEK (Figure 2B) and was significantly higher on TiAlV surfaces in comparison with both TCPS and PEEK. Levels were significantly higher on mmnTiAlV than activity on the sTiAlV surface. Likewise, osteocalcin production was increased only on the Ti alloy surfaces, with the effect being greater on mmnTiAlV (Figure 2C).

Bottom Line: Cells grown on mmnTiAlV had reduced levels of proinflammatory interleukins.Cells on PEEK had higher mRNAs for factors strongly associated with cell death/apoptosis, whereas cells on mmnTiAlV exhibited reduced cytokine factor levels.All results were significant (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: *Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA †SpineCare Medical Group, San Francisco Spine Institute, San Francisco, CA ‡Titan Spine, LLC, Mequon, WI §Department of Periodontics, The University of Texas Health Science Center at San Antonio, San Antonio, TX; and ¶Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA.

ABSTRACT

Study design: An in vitro study examining factors produced by human mesenchymal stem cells on spine implant materials.

Objective: The aim of this study was to examine whether the inflammatory microenvironment generated by cells on titanium-aluminum-vanadium (Ti-alloy, TiAlV) surfaces is affected by surface microtexture and whether it differs from that generated on poly-ether-ether-ketone (PEEK).

Summary of background data: Histologically, implants fabricated from PEEK have a fibrous connective tissue surface interface whereas Ti-alloy implants demonstrate close approximation with surrounding bone. Ti-alloy surfaces with complex micron/submicron scale roughness promote osteoblastic differentiation and foster a specific cellular environment that favors bone formation whereas PEEK favors fibrous tissue formation.

Methods: Human mesenchymal stem cells were cultured on tissue culture polystyrene, PEEK, smooth TiAlV, or macro-/micro-/nano-textured rough TiAlV (mmnTiAlV) disks. Osteoblastic differentiation and secreted inflammatory interleukins were assessed after 7 days. Fold changes in mRNAs for inflammation, necrosis, DNA damage, or apoptosis with respect to tissue culture polystyrene were measured by low-density polymerase chain reaction array. Data were analyzed by analysis of variance, followed by Bonferroni's correction of Student's t-test.

Results: Cells on PEEK upregulated mRNAs for chemokine ligand-2, interleukin (IL) 1β, IL6, IL8, and tumor necrosis factor. Cells grown on the mmnTiAlV had an 8-fold reduction in mRNAs for toll-like receptor-4. Cells grown on mmnTiAlV had reduced levels of proinflammatory interleukins. Cells on PEEK had higher mRNAs for factors strongly associated with cell death/apoptosis, whereas cells on mmnTiAlV exhibited reduced cytokine factor levels. All results were significant (P < 0.05).

Conclusion: These results suggest that fibrous tissue around PEEK implants may be due to several factors: reduced osteoblastic differentiation of progenitor cells and production of an inflammatory environment that favors cell death via apoptosis and necrosis. Ti alloy surfaces with complex macro/micro/nanoscale roughness promote osteoblastic differentiation and foster a specific cellular environment that favors bone formation.

Level of evidence: N/A.

Show MeSH
Related in: MedlinePlus