2. Academic Validation
  3. Injectable self-expanding short-fiber scaffold reduces endometrial hyperplasia

Injectable self-expanding short-fiber scaffold reduces endometrial hyperplasia

  • J Control Release. 2025 Aug 26:387:114172. doi: 10.1016/j.jconrel.2025.114172.
Yan Zhou 1,  Mingyue Liu 2,  Jingru Duan 3,  Chenjia He 4,  Meihan Xu 4,  Juan Huang 4,  Aijun Zhang 5,  Wenguo Cui 6,  Bufang Xu 7
Affiliations

Affiliations

  • 1 Department of Gynecology and Obstetrics of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • 2 Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • 3 Department of Gynecology and Obstetrics of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Laboratory of Reproduction Immunology, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University Shanghai Medical College, Shanghai 200032, China.
  • 4 Department of Gynecology and Obstetrics of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • 5 Department of Gynecology and Obstetrics of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: zhaj1268@163.com.
  • 6 Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: wgcui@sjtu.edu.cn.
  • 7 Department of Gynecology and Obstetrics of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Reproductive Medicine, Department of Histoembryology, Genetics and Developmental Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: bufangxu@163.com.
PMID: 40876546 DOI: 10.1016/j.jconrel.2025.114172
Abstract

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.

Keywords

Endometrial hyperplasia; Injectable; Self-expanding; Short-Fiber scaffold.

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