A. Schadenhofer, J. Körner
Leibniz University Hannover,
Germany
Keywords: hydrogels, in vitro reactive accelerated aging, material degradation, polymers
Summary:
Hydrogels are very promising candidates for use in implant technology and biomedical sensors due to their easily achievable biocompatibility and wide variety of base polymers they can be made of [1]. However, employing them for in vivo applications requires extensive testing to obtain clearance for medical use. In order to reduce time, cost and the need for corresponding animal experiments, novel in vitro methods for material degradation studies need to be developed [2]. One promising approach for that purpose is reactive accelerated aging (RAA). By exposing materials to harsher-than-life conditions, such as increased temperatures and reactive oxygen species (ROS), material degradation can be simulated at an accelerated rate. Thus far, the RAA approach has only been applied to neural implants, where results showed a good correlation to outcomes from animal studies. [3,4]. With the study presented here, we aim at extending the use of RAA towards polymer materials and have chosen synthetic stimulus-responsive (i.e. smart) hydrogels as first test candidates. This specific class of hydrogels possesses the ability to swell or shrink in response to an external stimulus which is furthermore dependent on the structural integrity of the material. Hence, this smartness offers an easy way of monitoring structural changes and material degradation by simply evaluating the swelling response. As an initial step, we have built an in vitro automated reactive accelerated aging (aRAA) assay similar to the one described in [3]. It comprises an aging chamber where a base of phosphate buffered saline solution with added hydrogen peroxide (H2O2) is continuously heated to 67 °C. This initiates the breakdown of H2O2 into reactive oxygen species that in turn cause degradation of the sample. Temperature, pH, conductivity and H2O2 concentration of the solution are continuously monitored and adjusted to stable values by automated addition of fresh PBS/H2O2-mixture throughout the aging process. The samples are placed in customized holders in the aging chamber to avoid dislocation and for convenient removal of samples from the setup. In initial experiments, we have aged different synthetic stimulus-responsive hydrogels and studied their changes over time by optical microscopy to identify mechanical damages such as cracks. Furthermore, weighing experiments were conducted to evaluate the swelling properties. As a next step, the aRAA results will be compared to previously published datasets from animal and human studies as well as cell-based assays to evaluate the validity of the approach in mimicking in vivo processes. Based on that, the aRAA procedure can be adjusted and optimized for broader use as a time and cost-efficient way to study degradation processes of polymer materials without the need for animal experiments. [1] Zhang et al., Front. Chem. 8:615665,2021; https://doi.org/10.3389/fchem.2020.615665 [2] Myers et al., ALTEX 34(4):479, 2017; https://doi.org/10.14573/ALTEX.1608081 [3] Caldwell et al., Biomat. 232:119731, 2020; https://doi.org/10.1016/j.biomaterials.2019.119731 [4] M. Street et al., Rev Sci Instrum 89(9):094301, 2018; https://doi.org/10.1063/1.5024686