Injectable self-expanding short-fiber scaffold reduces endometrial hyperplasia

Endometrial hyperplasia (EH), a precursor lesion to endometrial carcinoma, poses a significant challenge to women's health. However, current EH treatment involves a critical bottleneck because the rigid structures of conventional levonorgestrel (LNG)-releasing intrauterine system leads to poor adaptability. Here, we designed a novel self-expanding injectable intrauterine scaffold by first constructing a three-dimensional porous biomimetic extracellular matrix network via electrospinning. The elastic network was subsequently optimized through the thermal crosslinking-condensation reaction of polylactic acid and gelatin. By regulating the proportion of short nanofibers, we refined the microporous scaffold structure, enabling rapid self-expansion upon exposure to uterine fluid after injection and dynamic fit to the uterine cavity. The resulting scaffold efficiently loaded LNG through physical binding and exhibited excellent biocompatibility. In particular, it exerted therapeutic effects through a tripartite synergistic mechanism: suppressing excessive endometrial cell proliferation, promoting apoptosis in abnormal endometrial cells, and inhibiting pathological angiogenesis. In EH rat models, the scaffold effectively remodeled uterus morphology-reducing uterine wet weight from 0.91 ± 0.21 to 0.59 ± 0.11 g and restoring endometrial thickness from 558.2 ± 58.04 to 463.50 ± 61.01 μm, approaching the normal thickness of 420.4 ± 40.04 μm. It also significantly improved pathological features, with glandular density decreased from 22.97 ± 4.43 to 14.22 ± 4.27 per high power field (HP), close to the normal count of 14.28 ± 2.52 per HP. Our intelligent scaffold, with its injectability, self-expanding adaptability, and biomimetic therapeutic functions, may resolve the clinical limitations of conventional rigid intrauterine materials, enabling effective EH treatment.