Local Doxorubicin Delivery Via 3d-Printed Porous Scaffolds Reduces Systemic Cytotoxicity And Breast Cancer Recurrence In Mice

The concept of using macroscale porous scaffolds as local drug reservoirs to prevent cancer recurrence has received little attention. To extend the use of these scaffolds as drug delivery devices, the morphology needs to be optimized. Here, a porous scaffold that can work as efficient drug reservoirs is developed. A combination of additive manufacturing and salt leaching techniques to produce scaffolds of medical grade poly(epsilon-caprolactone) that has macroscale pores of 300-500 mu m and intrastrut microscale pores of 5-35 mu m in size is used. The chemotherapeutic drug, doxorubicin (DOX), is loaded onto the porous scaffolds by soaking with the loading efficacy as high as 90%. The DOX-loaded scaffolds display a biphasic monotonic drug release up to 28 d, and a dose-dependent chemotherapeutic effect against breast cancer cells, MDA-MB-231. Compared to one-time intravenous injection of 40 mu g DOX, implantation of scaffolds containing only 2 or 8 mu g of DOX after tumor removal in mice shows lower cardio-cytotoxicity, reduced local cancer recurrence, and is correlated with a lower metastasis progression in lungs, liver, and spleen in 28 d of treatment. These bimodal scaffolds are thus promising in the development of scaffolds in breast cancer after tumor removal.