3D polyurethane vaginal rings for the delivery of steroid hormones using material extrusion additive manufacturing

Three-dimensional printing has emerged as a novel technology to produce vaginal rings (VRs). However, the inherent high flexibility demanded by VRs poses a challenge when using filaments during the printing process. Here, we introduce a new approach for continuous 3D printing that eradicates the dependence on filaments and their printability for the fabrication of highly flexible VRs. Herein, Hot Melt Extrusion (HME) was used to create progesterone (PGR)-loaded thermoplastic polyurethane (TPU) pellets that were used as feedstock for 3D printing material extrusion of VRs. The TPU-based VRs presented excellent printability performance. Further physicochemical characterization indicated the presence of high amorphous PGR content while mechanical tests revealed that the VRs were consistently manufactured without significant deformation under prolonged compression and their performance was comparable to that of commercial VRs. The printed rings presented sustained release of clinically relevant quantities of progesterone over 28 days. Ex vivo studies showed that PGR permeated the porcine mucosa in a sustained manner for at least seven days. Finally, no cytotoxicity was observed in murine fibroblasts for the plain and progesterone-loaded pellets. This study demonstrates the potential of coupling HME and direct extrusion to produce 3D-printed VRs, aligning with the characteristics of traditional devices.