Impact of sterilization and oxidation processes on the additive blooming observed on the surface of polyurethane

Highlights

• Ionizing treatment leads to an increase in surface roughness.

• Roughness increase is smaller with oxidation processes.

• Bloomed crystals of additives can be damaged by oxidation treatment.

• Temperature rise during irradiation can lead to the melting of the bloomed species.

Abstract

The surface state is a major parameter for the biocompatibility of medical devices. During storage, the blooming of additives may occur on the surface of polymers and modify their properties. In this study, the impact of sterilizing and oxidation treatments on blooming was studied. The study was realized on polyurethane used in the fabrication of catheters on which the blooming of antioxidant crystals has been previously observed. Sterilization by ionizing radiations (beta, gamma) was performed on this material and samples were submitted to different kinds of oxidation process (UV, H₂O₂ and macrophages action). Surface evolution was investigated using AFM microscopy, FTIR-ATR and SEM.

Introduction

The behavior of a material under the effects of irradiation and oxidation is very important in the context of a medical device (MD) use. Evidently, all implantable MD must be sterile before being applied to patient but once in vivo they can undergo an oxidative stress due to a potential inflammatory reaction during their implementation [1].

This can lead to the modification of the implant or to its degradation associated with a chronic inflammation and to an isolation of the implant by fibrous encapsulation. As a foreign body, the MD indeed triggers an inflammatory response with the release of highly reactive oxidizing agents by the organism, such as oxidized halogens, oxidizing radicals, singlet oxygen. The sources of these oxidizing agents are phagocytic leukocytes (neutrophils, monocytes, and macrophages). After exposure to a material surface, the predominant ones in the acute and chronic steps of inflammation are the neutrophils and the monocyte-derived macrophages (MDM). MDM are activated by adhesion to the surface which is too large to be engulfed, hence MDM release reactive oxygen species and hydrolytic enzymes and fuse to form inflammatory giant cells. The precursor of highly reactive oxidizing agents is the superoxide O°⁻². The mild oxidant O°⁻² can indeed give birth to H₂O₂ and to OH°. Hydrogen peroxide can then be the origin of new OH° radicals, or of even more powerful oxidants such as HClO. It is generally considered that 20–70% of H₂O₂ is transformed in HClO by a specific enzyme, the myeloperoxidase [2], [3], [4], [5]. In vivo surrounding liquid media are constantly renewed; moreover there may be a synergetic effect of several pathways of degradation for the material and generation of high local concentration of reactive oxygen intermediates because of the closed compartment created by adherent macrophage between the cells and the polymer device surface [6], [7].

Sterilization can be processed by different methods: autoclaving if high temperature is tolerated by the materials, ethylene oxide exposition or ionizing radiations. The sterilization by radiation has been studied for more than 50 years; it is intended for non-reusable materials and is very suitable for the sterilization of large quantities of already packaged devices such as catheters. In this case, industrial accelerators with gamma radiations or with electrons of high energy (10 MeV) and high power (10–20 kW) are generally used. For gamma treatment, photons are emitted from an isotope source (Cobalt 60 for example) producing ionization throughout the treated product. Several types of parameters should be taken into account: of course, the absorbed dose, but also the dose rate, and the radiation energy. The recommended dosage for sterilization is of 25 kGy (European Pharmacopoeia). The process takes from several minutes for electrons sterilization to hours for gamma rays.

We have chosen to focus our study on polyurethane catheters which can be used as implantable MD and to study the impact of sterilizing and oxidizing treatments on additive blooming. This blooming is a phenomenon that can occur on the surface of the material. We have previously shown that poly(ether urethane) catheters of Pellethane 2363^® could be subjected to the blooming of the antioxidant Irganox 1076^® if they were exposed to a long storage at a low temperature [8], [9]. Better knowledge of the behavior of such surfaces with blooming is crucial for several reasons:

• The surface is the part of the device that is directly in contact with the biological environment: blooming can thus significantly impact the MD biocompatibility and all the bioadhesion phenomena (bacteria, proteins…) [10], [11], [12].

• Several authors reported that the oxidative mechanism of poly(ether urethane) degradation can be inhibited by the use of antioxidants as additives [13], [14]. Non-protected samples were cracked and pitted unlike the protected ones; low degradation was observed by FTIR in polyether segments (soft segments) and no degradation was put into evidence in segments containing the urethane groups (hard segments) on the contrary to what was observed to the non-protected PU [14].

The behavior of polyurethane (PU) under the effect of oxidative stress was studied in vivo and in vitro by numerous authors [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28]. In particular, these studies revealed that polyether-based polyurethanes and Pellethane 2363-80A^® used in pacemaker lead have failed [29] as they suffered from localized cracking and frosting. These defects were due to an “environmental stress cracking” characterized by mechanical, oxidative stresses, the presence of certain biological entities and metal ion oxidation (MIO) if the material is in direct contact with metal ions from conductor coils. The MIO mechanism involves the interaction between the metal of the conductor coil and hydrogen peroxide. To observe in vitro large ductile cracks as those observed in vivo, it was necessary to contact PU with blood plasma (and more particularly with the α₂ macroglobulins) and then to submit PU to an oxidizing solution (10% H₂O₂ + CoCl₂) [19].

The effect of sterilizing treatment on this same Pellethane^® catheter has been previously studied by our research group and we have demonstrated that the e-beam treatment induces polymer chain scissions and branchings as well as a decrease in antioxidant (AO) Irganox 1076^® ratio in the polymer [30].

In the present work we have thus chosen to study different kinds of systems to explore the consequences of blooming on the oxidation and sterilization treatments of PU:

• The catheter as a MD with an important blooming of Irganox 1076^® on its surface: it is a commercial system with a relatively complex surface state due to strong initial roughness of the device.

• A spincoated catheter-based film: the catheter was dissolved and spincoated on a silicon wafer before study; the aim was to highlight surface variations of a sample with the same composition as the catheter but being much smoother and consequently adapted to AFM microscopy measurements.

We have then examined the behavior of these devices:

• Under sterilizing treatments: a gamma irradiation under soft and oxygenated conditions and a beta irradiation with high dose rates were used.

• Under oxidative stress: we compare a standard oxidation process due to UV exposition (artificial accelerated weathering) to the effect of a storage in an oxidative liquid medium (H₂O₂ 20%) and to the effect of macrophage adhesion on the surface·H₂O₂ was chosen to simulate the complex in vivo oxidizing environments created at the cell-material interface.

The effect of these treatments was investigated using spectroscopy (FTIR) and microscopy (AFM, optical, SEM).