Redox responsive 3D-printed nanocomposite polyurethane-urea scaffold for Doxorubicin local delivery

Loading anti-cancer drugs into 3D polymeric platforms is a promising strategy for achieving sustained release to solid cancer tissues while simultaneously prolonging device retention and promoting regeneration. In this study, we developed a drug-loaded 3D nanocomposite scaffold based on polyurethane urea (PUU) using the 3D solvent-casting technique. The purpose was to achieve sustained local delivery and redox-responsive release of doxorubicin, thereby preventing local bone cancer recurrence in post-operative resection sites.Specifically, redox responsive PUUs, achieved using the tri-block copolymers PCL-PEG-PCL as soft segment and the tetramethylester of L-glutathione as chain-extender, has been selected to standardize suitable 3D printing procedure. Initially, a series of PUUs was synthesized and characterized. The suitability of the 3D printing procedure was assessed using dichloromethane on polymeric dispersions with and without hydroxy-apatite nanoparticles (nHAp). In particular, the release studies confirm redox responsive release with less of 30% of drug released over a period of 21 days. Moreover, hydrolytic degradation studies have demonstrated the stability and resistance of 3D printed scaffolds over time, which is fundamental requirement for long-term controlled release systems. Finally, in-vitro studies showed the cytocompatibility of the scaffolds towards MC3T3-E1 and in-vitro cytotoxicity experiments confirmed the high cytotoxicity effect of drug-loaded scaffolds on HCT-116 cells used as cancer model cells.