Fabrication of 3D Printed, Core-and-Shell Implants as Controlled Release Systems for Local siRNA Delivery

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Regenerative Medicine

Background:

• Clinical translation of small interfering RNA (siRNA) therapies is hindered by poor pharmacokinetics.
• 3D printing offers a platform for localized, sustained siRNA delivery via personalized implants.
• Hydrogels provide a promising alternative to rigid implants, mimicking tissue properties.

Purpose of the Study:

• To formulate a thermoresponsive composite hydrogel for extrusion 3D printing.
• To fabricate controlled-release implants for local and sustained siRNA delivery.
• To investigate the release kinetics and integrity of siRNA-Lipofectamine RNAiMAX complexes from the implants.

Main Methods:

• A thermoresponsive hydrogel was formulated using agarose, pluronic F127, and gelatin.
• Core-and-shell 3D-printed implants were fabricated to protect siRNA from thermal stress.
• siRNA-Lipofectamine RNAiMAX complexes were loaded into the core, with release controlled by printing patterns.

Main Results:

• The implants demonstrated sustained release of siRNA complexes for up to one month.
• The integrity of released siRNA complexes was confirmed up to eight days.
• Varying printing patterns allowed for tailored control over siRNA release profiles.

Conclusions:

• Thermoresponsive hydrogel implants fabricated via 3D printing can achieve sustained and controlled local delivery of siRNA.
• The core-and-shell design effectively protects siRNA from thermal degradation during printing.
• This technology holds potential for advancing siRNA-based therapeutics with improved pharmacokinetic profiles.