Three-Dimensional Printing Multi-Drug Delivery Core/Shell Fiber Systems with Designed Release Capability.

A hydrogel system with the ability to control the delivery of multiple drugs has gained increasing interest for localized disease treatment and tissue engineering applications. In this study, a triple-drug-loaded model based on a core/shell fiber system (CFS) was fabricated through the co-axial 3D printing of hydrogel inks. A CFS with drug 1 loaded in the core, drug 2 in the shell part, and drug 3 in the hollow channel of the CFS was printed on a rotating collector using a co-axial nozzle. Doxorubicin (DOX), as the model drug, was selected to load in the core, with the shell and channel part of the CFS represented as drugs 1, 2, and 3, respectively. Drug 2 achieved the fastest release, while drug 3 showed the slowest release, which indicated that the three types of drugs printed on the CFS spatially can achieve sequential triple-drug release. Moreover, the release rate and sustained duration of each drug could be controlled by the unique core/shell helical structure, the concentration of alginate gels, the cross-linking density, the size and number of the open orifices in the fibers, and the CFS. Additionally, a near-infrared (NIR) laser or pH-responsive drug release could also be realized by introducing photo-thermal materials or a pH-sensitive polymer into this system. Finally, the drug-loaded system showed effective localized cancer therapy in vitro and in vivo. Therefore, this prepared CFS showed the potential application for disease treatment and tissue engineering by sequential- or stimulus-responsively releasing multi-drugs.