Work Item
ASTM WK88084

New Practice for Maintaining oxidative capacity of test solutions for oxidative degradation testing of non-absorbable polymers

1. Scope

1.1 It is the intent of this practice to permit an investigator to maintain oxidative capacity of test solutions and provide a standardized approach for oxidative degradation screening of polymers as recommended in ISO 10993-13. The method described in this practice can be used for real-time monitoring and maintaining hydrogen peroxide (H2O2) concentrations in aqueous test solutions within a consistent range for oxidative degradation tests at ambient and elevated temperatures for prolonged periods. Due to the sensitivity of electrochemical components used in this method, the stability range of the H2O2 concentration in the test solutions may vary between test systems and shall be reported by the user of this practice.

1.2 Although the method described in this practice could be used for oxidative degradation screening of non-absorbable polymers, it is recognized that this method may not precisely simulate the degradative mechanisms for a polymeric medical device after implantation. This practice considers polymer degradation by hydrolytic and oxidative chemical pathways of the finished polymeric device. It is not applicable to degradation of the device induced during its intended use by mechanical stress, wear, electromagnetic radiation, or biological factors such as enzymes, other proteins or cellular activity.

1.3 The values presented in this practice adhere to SI units as the standard. Any conversion to alternative units is provided for informational purposes only. It is the responsibility of the user to ensure safety, health, and environmental practices in accordance with regulatory requirements.

1.4 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.

Keywords

accelerated testing; oxidative degradation; polymers; oxidative screening; oxidative capacity

Rationale

X1.1 ISO 10993-13 recommends the identification and quantification of degradation products of non-absorbable polymeric implants. If the service environment cannot be simulated, ISO 10993-13 suggests an initial screening for oxidative polymer degradation using either a 3% H2O2 aqueous solution or Fenton’s reagent (mixture of dilute hydrogen peroxide solution and iron(II) salts, e.g. 100 µmol Fe2+ and 1 mmol H2O2). Since the H2O2 solutions may not remain stable at elevated temperatures or over prolonged periods, ISO 10993-13 recommends that users specify, justify, and report the stability range but does not provide a specific test method to maintain oxidative capacity of the test solutions. Most in vitro oxidative stability screening tests for non-absorbable polymers, as reported in peer-reviewed literature, use very high concentrations of H2O2 (~ 3 – 30 % w/w) and involve manual replacement of the H2O2 media every 3 – 7 days but do not monitor the actual H2O2 concentration in the test solution. H2O2 is known to be unstable, with reported half-lives ranging from a few seconds to several days. The H2O2 decomposition mechanism and kinetics depends on various test conditions, including testing temperature, solution pH, sample geometry and materials chemistry, composition of test solution (e.g. phosphate buffer solution vs water), and the surface of the reaction vessel. Because by-products of H2O2 decomposition, such as hydroxyl radicals, superoxide anion radicals, hydroperoxyl radicals, can react with the polymer, the oxidative capacity of test solutions depends not only the concentration of H2O2 in the test solution but also on H2O2 decomposition mechanism and kinetics. The variability in oxidative capacity of the test solutions due to varying H2O2 concentrations and test conditions can impact comparisons between test results and complicate data interpretation.

X1.2 The use of excessively high H2O2 concentrations compared to physiological reactive oxygen species (ROS) concentrations and elevated test temperatures could lead to mechanistic changes in the dominant chemical degradation pathway in the polymer or introduce spatial variation in physical and mechanical properties due to diffusion-limited oxidation (DLO). Mechanistic variations due to changes in the dominant chemical degradation pathway at elevated temperatures or potential presence of DLO, implies that the chemistry extrapolated from the accelerated high temperature aging conditions may not reflect the chemistry occurring in the polymer under lower temperature physiologically relevant aging conditions. Therefore, the H2O2 concentration for the screening test should be selected such that it can expedite the polymer oxidative degradation process while remaining representative of the degradation mechanism at physiologically relevant ROS concentrations.

X1.3 Implantation of a foreign material like a polymeric implant in the body involves a cascade of reactions as part of the immune response. In the case of some implants, a chronic inflammatory response may occur resulting in oxidative stress. Oxidative stress occurs due to the imbalance between generation of various oxidizing chemical species such as reactive oxygen species (ROS) like superoxide anion radicals, hydrogen peroxide (H2O2), hypochlorous acid, and reactive nitrogen species (RNS), and the cellular reducing capabilities. Although H2O2 occurs in normal metabolism in mammalian cells, it is also a key metabolite in oxidative stress, and supraphysiological concentrations of H2O2 (>100 nM) have been associated with damage of biomolecules. In addition to ROS produced by the body, free radicals may be introduced or generated in the polymer during manufacturing, processing, or shelf-storage.15

X1.4 The properties of implanted polymers, including their composition, size, shape, surface properties, mechanical properties, and degradation products, both influence and are influenced by oxidative stress. The material and its degradation byproducts contribute to the local oxidative stress levels and may also stimulate further oxidant formation, leading to prolonged oxidant exposure. The constant oxidative attack by inflammatory cells is one of the main causes of in vivo degradation of some polymers. For example, Polyether polyurethane used as electrical insulation on pacemaker leads failed due to the effects of oxidative degradation combined with mechanical stress (environmental stress cracking).18 Implants made of polyolefins like polyethylene (facial implants, arthroplasty liners) and polypropylene (surgical mesh) are also susceptible to oxidative degradation due to the chemical nature of their polymeric backbone. Similarly, polyethylene glycol (PEG), commonly used in anti-fouling coatings, and polyimide and Parylene-C coated neural electrodes have been reported to be prone to oxidative degradation under physiologically relevant conditions.

X1.5 Processes like crosslinking or the presence of antioxidants could inhibit or delay, but may not entirely prevent, oxidative degradation of some polymers. Additionally, oxidative degradation of some polymers involves formation and accumulation of hydroperoxide radicals before significant oxidation is observed. Therefore, absence of observable oxidation in limited time tests may not be indicative of the polymer’s long-term stability.

X1.6 The electrochemical detection of hydrogen peroxide (H2O2) plays a key role in several analytical tools and numerous electrode materials have been investigated. The hydroxyl radical was identified as a key intermediate species underlying the voltametric detection of H2O2. However, the linearity of the calibration between standard H2O2 concentrations and the electrode signals is usually limited to low H2O2 concentrations. Chronoamperometry protocols have been used for real-time continuous monitoring of H2O2 concentration for in vitro assessment of oxidative stability of neural electrodes. Similar chronoamperometry protocols were also used for assessing oxidative stability of polypropylene surgical mesh in vitro.

The title and scope are in draft form and are under development within this ASTM Committee.

Details

Developed by Subcommittee: F04.15

Committee: F04

Staff Manager: Kathleen Chalfin

Work Item Status

Date Initiated: 10-10-2023

Technical Contact: David Simon

Item: 000

Ballot:

Status: