Long-term in vivo degradation and biocompatibility of degradable pHEMA hydrogels containing graphene oxide

Developing biocompatible, non-fouling and biodegradable hydrogels for blood-contacting devices re-mains a demanding challenge. Such materials should promote natural healing, prevent clotting, and undergo controlled degradation. This study evaluates the biocompatibility and biodegradation of degradable poly(2-hydroxyethyl methacrylate) (d-pHEMA) hydrogels with or without reinforcement with oxidized few-layer graphene (d-pHEMA/M5ox) in a long term implantation in rats, assessing non-desired side-effects (irritation, chronic toxicity, immune response).Subcutaneous implantation over 6 months revealed degradation of both hydrogels, despite slower for d-pHEMA/M5ox, with degradation products found in intracellular vesicles. No inflammation nor infection at implantation areas were observed, and no histopathological findings were detected in parenchymal organs. Immunohistochemistry confirmed d-pHEMA and d-pHEMA/M5ox highly anti-adhesiveness. Gene expression of macrophages markers revealed presence of both M1 and M2 macrophages at all timepoints. M1/M2 profile after 6 months reveals an anti-inflammatory environment, suggesting no chronic inflam-mation, as also demonstrated by cytokines (IL-alpha, TNF-alpha and IL-10) analysis.Overall, modification of pHEMA towards a degradable material was successfully achieved without evoking a loss of its inherent properties, specially its anti-adhesiveness and biocompatibility. There-fore, these hydrogels hold potential as blank-slate for further modifications that promote cellular adhe-sion/proliferation for tissue engineering applications, namely for designing blood contacting devices with different load bearing requirements.