Speaker
Description
Introduction
Poly(alkylene citrate)s – (PACs) are widely studied as candidates to produce temporary medical devices such as blood vessel prostheses, wound dressings, drug delivery systems, scaffolds, and matrices for tissue engineering. The advantages of PACs are susceptibility to hydrolytic degradation and the possibility of modification with free radical scavengers, which are known to tune inflammation and thus the tissue healing process. Glutathione (GSH) is an excellent antioxidant, efficiently scavenging of a wide variety of free radicals. The aim of this study was to find out if the chemical composition of PACs (GSH content, type of diol) influences the degradation kinetics and cytocompatibility of the resulting polymers.
Methodology
Two PACs: cross-linked poly(hexamethylene citrate) (cPHC) and poly(octamethylene citrate) (cPOC) with a molar ratio of citric acid to 1,6-hexanediol/1,8-octanediol equal to 2:3 without or with 0.4% or 0.8% GSH were synthesised [1]. For degradation studies, the samples were incubated in purified water at 37 oC up to 3 months. Then, the samples were weighed in a wet state and after freeze drying to evaluate weight loss and water absorption capacity, respectively. The hardness was assessed using Shore A method to evaluate the decrease in cross-linking density. Moreover, the pH of the incubation fluid was measured to study the degradation progress, while mass spectrometry was used to determine degradation products. In vitro cytocompatibility study of the PACs was performed using L929 fibroblasts, which were cultured in the 10% extracts of cPHC and cPOC samples with or without GSH. After 24 h and 72 h of culture, the Alamar blue metabolic activity and live-dead tests were performed.
Results
All PACs lost transparency with extending incubation time; the increase in swelling, viscosity, and adhesiveness of the samples were all observed. Furthermore, the GSH-modified samples lost their brown coloration as a function of incubation time. The weight loss was higher for cPHC than in case of cPOC samples which was attributed to higher hydrophilicity of materials prepared from shorter chain diol. Analysis of the mass spectra of the supernatants after the degradation process showed that small amounts of polymer chain fragments were released during the first 3 weeks of incubation and then the intensity of these characteristic peaks increased. The unit of citric acid appeared sporadically and in small amounts in the initial stages of degradation, although its intensity increased sharply from the the 5th week (cPHC) and from 8th week (cPOC), which, in turn, proves that cPOC samples degrade more slowly.
Conclusions
Performed studies show that degradation of POC is slow and homogeneous, which is promising in terms of reducing the body's immune response. Biological studies with L929 cells did not show cytotoxicity of the materials, which indicates the right direction for the use of GSH to improve the biocompatibility of citric acid polyesters.
Acknowledgements
This study was supported by the National Science Centre Poland (No 2018/28/C/ST5/00461) and by the Program ‘Excellence Initiative – Research University’ for the AGH University of Science and Technology.
References
Koper et al., Journal of Materials Chemistry. B, 2021, 9(32), 6425–6440
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