3D-Printed core-shell tablet for effective oral delivery of AT-MSC secretome in inflammatory bowel disease therapy

Inflammatory bowel disease (IBD) is a complex condition often treated with immunosuppressants, corticosteroids, or biologics, but these therapies can have limited effectiveness and significant side effects. In recent years, mesenchymal stromal cell (MSC) therapies have emerged as a promising alternative due to their ability to regulate immune responses. However, delivering live cells in patients carries risks such as rejection and short circulation times. As a result, researchers are increasingly exploring MSC secretome – the mixture of therapeutic proteins and growth factors released by these cells, as a safer, cell-free therapy.

Delivering secretome orally is challenging because its proteins are highly sensitive and can be degraded in the stomach before reaching the intestine. In addition, secretome therapies often require flexible dosing, which conventional formulations struggle to achieve.

To address this, we developed a 3D-printed core–shell tablet for oral delivery of adipose-derived MSC secretome. The secretome was freeze-dried and incorporated into an alginate hydrogel core, surrounded by a gastro-resistant Eudragit shell produced using semi-solid extrusion 3D printing. This design protects the proteins in gastric conditions and enables their release in the intestine.

The tablets showed strong mechanical properties and remained intact in acidic conditions, releasing their contents under intestinal pH through controlled, non-Fickian release. Overall, this work demonstrates the first solid oral dosage form capable of delivering MSC secretome, highlighting the potential of 3D printing for personalised IBD therapies.

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