TNF-a-Inhibition Improves the Biocompatibility of Porous Polyethylene Implants In Vivo
10.1007/s13770-020-00325-w
- Author:
Timon HUSSAIN
1
;
Donata GELLRICH
;
Svenja SIEMER
;
Christoph A. REICHEL
;
Jonas ECKRICH
;
Dimo DIETRICH
;
Shirley K. KNAUER
;
Roland H. STAUBER
;
Sebastian STRIETH
Author Information
1. Walter Brendel Centre of Experimental Medicine, LudwigMaximilians-University Munich, Marchioninistr. 27, 81377 Munich, Germany
- Publication Type:O RI G I N A L A R T I C L E
- From:
Tissue Engineering and Regenerative Medicine
2021;18(2):297-303
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 a (TNFa) 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:TNFa 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 ± 880.16 (uncoated implants) vs. 3939.09 mm-2 ± 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.
