A multistage drug delivery system via 3D-printed personalized TPU scaffold and microfluidic microspheres for nurse-led outpatient treatment of endometrial cancer

Abstract

Finding effective, fertility-preserving therapies for early-stage endometrial cancer (EC) and its precursor, atypical endometrial hyperplasia (AEH), remains a major clinical challenge. Conventional intrauterine devices (IUDs) often fail due to anatomical mismatches that cause displacement and treatment inefficacy. Here, a patient-specific intrauterine system that integrates a customizable 3D-printed thermoplastic polyurethane (TPU) scaffold with a multistage drug delivery platform for localized and sustained therapy is proposed. Monodisperse levonorgestrel-loaded PLGA microspheres were embedded in a methacrylated silk fibroin (SilMA) hydrogel matrix within the scaffold. Results indicate that the device enables controlled release of drugs over 90 days through a diffusion-swelling-degradation mechanism while minimizing the initial burst. Computational modeling confirmed the superior drug distribution of the T-shaped design. Furthermore, both in vitro and in vivo evaluations via subcutaneous implantation demonstrated excellent biocompatibility of such a system. This long-acting, mechanically adaptive, and patient-tailored system overcomes the key limitations of existing devices, validating the design of a biocompatible delivery platform as a foundation for future therapeutic efficacy studies for the conservative treatment of EC and AEH.