Regenerating the uterus: translational advances in endometrial bioengineering and immunotherapeutics

Uterine disorders, such as thin endometrium and intrauterine adhesions, remain significant challenges in reproductive medicine, often leading to infertility and poor pregnancy outcomes. Recent advances in regenerative medicine and tissue engineering have led to the development of innovative therapeutic strategies aimed at restoring endometrial structure and function. Biomaterials play a central role in these advancements, serving not only as structural scaffolds and delivery vehicles for stem/progenitor cells and bioactive molecules but also as modulators of the tissue microenvironment by promoting angiogenesis and regulating immune responses. Mesenchymal stem cells from various sources, including female reproductive tissues, along with their extracellular vesicles, have demonstrated potential in promoting angiogenesis, reducing fibrosis, and modulating immune responses for endometrial repair. Additionally, platelet-rich plasma and a range of pharmacological agents—often with advanced drug delivery systems, such as nanocarriers—further contribute to endometrial regeneration. Engineered scaffolds, particularly those derived from decellularized extracellular matrix or fabricated using three-dimensional bioprinting technologies, closely mimic the biomechanical and biochemical properties of native endometrium. These scaffolds facilitate cellular engraftment and provide valuable platforms for in vitro modeling of endometrial physiology. The development of uterus-derived extracellular matrix scaffolds with immunologically compatible biomaterials and organoids marks a pivotal step toward reducing immune rejection and improving clinical applicability. This review highlights recent progress in biomaterial-based therapeutics for uterine regeneration and discusses the remaining challenges in shifting therapeutic paradigms of personalized and tissue-specific regenerative strategies. Similar content being viewed by others Data availability Data sharing does not apply to this article as no datasets were generated or analyzed during the current study.

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All figures were created with Biorender.com. Funding This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIT) (RS-2024-00338274 to YJK and RS-2025-00517458 to HS), by Korean Fund for Regenerative Medicine (KFRM) funded by Ministry of Science and ICT, and Ministry of Health and Welfare, Republic of Korea (22A0106L1 to YJK and RS-2025-02223118 to HS), by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (RS-2025-02215684 to HS), and by Basic Science Research Program through the NRF funded by the Ministry of Education (RS-2019-NR40073 to HS). Author information Authors and Affiliations Contributions YJK and HS conceived the initial concept of the article; DL and YJK performed the literature search; DBL, YSK, and HS drafted and/or critically revised the work. All authors read and approved the final manuscript. Corresponding authors Ethics declarations Competing interests Authors declare no other financial or non-financial interests related to this work except for the funding acknowledged. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Lee, D., Kang, YJ. & Song, H. Regenerating the uterus: translational advances in endometrial bioengineering and immunotherapeutics. Semin Immunopathol 47, 36 (2025). https://doi.org/10.1007/s00281-025-01063-8 Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s00281-025-01063-8