"Fabrication of 3d Printed, Core-and-Shell Implants as Controlled Release Systems for Local Sirna Delivery".

The development and clinical translation of siRNA therapies remains challenging owing to their poor pharmacokinetics. The 3D printing technology presents a great opportunity to fabricate personalized implants for local and sustained delivery of siRNA. Hydrogels can mimic the mechanical properties of tissues avoiding the problems associated with rigid implants. Herein, we aimed to formulate a thermoresponsive composite hydrogel suitable for extrusion 3D printing to fabricate controlled-release implants loaded with siRNA-Lipofectamine RNAiMAX TM complexes. We selected a hydrogel matrix mainly composed of uncharged agarose to protect siRNA from decomplexation. Additionally, pluronic F127 and gelatin were added to improve the printability, degradation and cell adhesion to agarose implants. To avoid exposing siRNA to thermal stress during the printing process, we set up a core-and-shell design for our implants in which a core of siRNA-complexes loaded-pluronic F127 was printed without heat, and enclosed with a shell comprising the thermoresponsive composite hydrogel. We envisioned to control the release profile of siRNA-complexes by varying the printing patterns. Our results revealed that the implants could sustain the release of siRNA for 1 month. We proved the intactness of the released siRNA-complexes till the 8 th day. Furthermore, by changing the printing patterns we could tailor the release profiles. This article is protected by copyright. All rights reserved.