Biocompatibility assessment of cyclic olefin copolymers: Impact of two additives on cytotoxicity, oxidative stress, inflammatory reactions, and hemocompatibility

Abstract

This work reports the biocompatibility evaluation of cyclic olefin copolymers (COC) as candidates for implantable medical devices. The focus was to establish the influence of two major additives (antioxidant and lubricant) on the overall biocompatibility. The cytotoxicity was evaluated according to ISO 10993-5 guidelines using L929 fibroblasts, HUVEC, and THP-1-derived macrophages. Oxidative stress (ROS, GSH/GSSG, and SOD analysis) and pro-inflammatory cytokines (Il-6 and TNF-α secretion) were quantified using THP-1 cells in direct contact with films. Hemocompatibility was assessed through haemolysis testing, dynamic blood coagulation, platelet adhesion, and activation (membranous P-selectin expression). Results show that the different types of COC have successfully passed the in vitro biocompatibility tests. The presence of antioxidant induces however a slight decrease in ROS production in correlation with a high SOD activity and a modification in blood coagulation profile probably linked to antioxidant recrystallization phenomenon on the surface of COC. The lubricant presence reduced haemolysis, fibrinogen adhesion, and platelet activation. Surface nanotopography of COC highlights different types of needles and globules according to the present additive. Those primary results indicate that COC are promising biomaterial. However, additives influenced some biological parameters pointing out the necessity of a global approach of risk analysis for biocompatibility evaluation. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3333-3349, 2017.

Berberine-Incorporated Shape Memory Fiber Applied as a Novel Surgical Suture

“…In vitro cytotoxicity of the fibers was assayed according to ISO 10993 part 5 guidelines 3 (Bernard et al, 2017). Extract was prepared by the incubation of 0.2 g of each fiber with 1 ml of Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 100 mg/ml penicillin, and 100 mg/ml streptomycin for 48 h at 37°C.…”

Differences in biocompatibility of microneedles from cyclic olefin polymers with human endothelial and epithelial skin cells

“…14 Different additives have already been shown to have an effect on cytotoxicity and inflammation. 15 In this article, we show that different COP materials have varying degrees of biocompatibility with human skin cell types. We have found that these differences are not obvious from standard cytotoxicity testing methods as described in USP <87> 16 and EU ISO 10993-5, 17 but can be shown by the assessment of inflammation and differentiation markers in human cells in vitro.…”

“…However, the different compositions and monomers that make up commercially available medical grade polymers have raised questions about biocompatibility testing of these materials . Different additives have already been shown to have an effect on cytotoxicity and inflammation …”

A Review of Design Considerations for Hemocompatibility within Microfluidic Systems

“…52 COPs have been explored as promising candidates with regards to biocompatibility and material hemocompatibility. 53 And it has been demonstrated that the hemocompatibility of COPs can be significantly increased with various additives and surface modification techniques. [53][54][55] Polymethyl Methacrylate PMMA, is an amorphous plastic with 99% light transmission and scratch resistance.…”

“…53 And it has been demonstrated that the hemocompatibility of COPs can be significantly increased with various additives and surface modification techniques. [53][54][55] Polymethyl Methacrylate PMMA, is an amorphous plastic with 99% light transmission and scratch resistance. 56 Light transmission is essential in devices requiring microscopy or other optical end points.…”