KMID : 1377020210180020297
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Tissue Engineering and Regenerative Medicine 2021 Volume.18 No. 2 p.297 ~ p.303
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TNF-¥á-Inhibition Improves the Biocompatibility of Porous Polyethylene Implants In Vivo
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Hussain Timon
Gellrich Donata Siemer Svenja Reichel Christoph A. Eckrich Jonas Dietrich Dimo Knauer Shirley K. Stauber Roland H. Strieth Sebastian
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Abstract
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Background: To improve the biocompatibility of porous polyethylene (PPE) implants and expand their application range for reconstructive surgery in poorly vascularized environments, implants were coated with tumor necrosis factor ¥á (TNF¥á) inhibitor Etanercept. While approved for systemic application, local application of the drug is a novel experimental approach. Microvascular and mechanical integration as well as parameters of inflammation were analyzed in vivo.
Methods: PPE implants were coated with Etanercept and extracellular matrix (ECM) components prior to implantation into dorsal skinfold chambers of C57BL/6 mice. Fluorescence microscopy analyses of angiogenesis and local inflammatory response were thrice performed in vivo over a period of 14 days to assess tissue integration and biocompatibility. Uncoated implants and ECM-coated implants served as controls.
Results: TNF¥á inhibition with Etanercept led to a reduced local inflammatory response: leukocyte-endothelial cell adherence was significantly lowered compared to both control groups (n?=?6/group) on days 3 and 14, where the lowest values were reached: 3573.88 leukocytes/mm-2?¡¾?880.16 (uncoated implants) vs. 3939.09 mm-2?¡¾?623.34 (Matrigel only) vs. 637.98 mm-2?+?176.85 (Matrigel and Etanercept). Implant-coating with Matrigel alone and Matrigel and Etanercept led to significantly higher vessel densities 7 and 14 days vs. 3 days after implantation and compared to uncoated implants. Mechanical implant integration as measured by dynamic breaking strength did not differ after 14 days.
Conclusion: Our data show a reduced local inflammatory response to PPE implants after immunomodulatory coating with Etanercept in vivo, suggesting improved biocompatibility. Application of this tissue engineering approach is therefore warranted in models of a compromised host environment.
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KEYWORD
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Porous polyethylene, Etanercept, Implant integration, Fluorescence microscopy, ECM
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