TNF-α-Inhibition Improves the Biocompatibility of Porous Polyethylene Implants In Vivo

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 α (TNFα) 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: TNFα 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.

Surface Modification of Porous Polyethylene Implants with an Albumin-Based Nanocarrier-Release System

“…Additionally, for the investigation of encapsulation of a low molar substance, effects on the encapsulation of a high molecular substance were investigated. SR101-labeled Etanercept was chosen as a representative substance due to its large molecular size (~150 kDa) and promising effects regarding the inflammatory response of PPE implants in vivo as recently described [55]. Intravital microscopy showed optically visible fluorescence of the PPE implants in both groups throughout the entire experimental period (Figure 6).…”

“…Furthermore, considering the stability of the albumin nanocarriers, evaluation of specific effects of encapsulation might also be influenced by the limited observation period when using the dorsal skinfold chamber model. Additionally, the observational quality can be improved by intravascular application of fluorophores allowing a more precise evaluation of the vascular network [23,48,49,55]. Therefore, further experiments evaluating the influence of surface modification with albumin nanocarriers on biological effects are urgently needed and longer observation periods should be considered to determine the specific effect of encapsulation especially when high molar substances are encapsulated.…”

IsoMAG—An Automated System for the Immunomagnetic Isolation of Squamous Cell Carcinoma-Derived Circulating Tumor Cells

“…Due to the highly versatile construction and design of the device, it is possible to implement such additional purification steps to the automated IsoMAG protocol. Moreover, the biocompatibility of micro/nanocarriers may be affected by biomolecule corona formation [26,42,43]. It is accepted that when micro/nanocarriers enter physiological environments, proteins and other biomolecules bind to their surfaces, leading to the rapid formation of a biomolecule corona [44].…”