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 tetramethyl-ester 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 hydroxyapatite 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.