Novel injectable sodium alginate hydrogel developed for improved endometrial repair with human umbilical cord mesenchymal stem cells

This study presents a novel injectable sodium alginate hydrogel designed to enhanc stem cell therapy for endometrial regeneration. Using calcium gluconate as a crosslinking agent, we achieved improved homogeneity and injectability compared to traditional calcium chloride crosslinking. RGD modification further enhanced cell adhesion, proliferation, and differentiation in vitro, creating a bioactive scaffold for umbilical cord mesenchymal stem cells (UCMSCs) delivery. In a mouse model of endometrial injury, intrauterine transplantation of RGD-modified hydrogel encapsulating UCMSCs significantly improved endometrial thickness, reduced fibrosis, enhanced angiogenesis, and increased pregnancy rates compared to both untreated controls and UCMSCs alone. These results suggest that this injectable hydrogel system combined with stem cells holds significant promise for future applications in treating endometrial damage and improving reproductive outcomes in women. Graphical Abstract Similar content being viewed by others Data availability The raw/processed data required to reproduce these findings cannot be shared at this time due to technical or time limitations. Change history 18 April 2025 Author equal contribution statement was added.

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We thank Dr. Yihan Wan (School of Life Sciences, West Lake University) for her kind suggestions. Funding This work was supported by the National Natural Science Foundation of China (32170800 and 31871490) and the National Key Research and Development Program of China (2018YFA0800100). It is also supported by the Fundamental Research Funds for the Central Universities (22120240435). Author information Authors and Affiliations Contributions J. X. and YY. L., designed the research; YF. L., WM. Y. and RX. Wang., conducted the experiments; HQ. D assisted with the experiments; LH. S. and YY. L. provided technical and resource support; J. X. and YF. L. wrote the manuscript. All authors read and approved the final manuscript. Corresponding authors Ethics declarations Conflict of interest None declared. Additional information Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Author equal contribution statement was added. 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 Li, Y., Yin, W., Dong, H. et al. Novel injectable sodium alginate hydrogel developed for improved endometrial repair with human umbilical cord mesenchymal stem cells. Drug Deliv. and Transl. Res. 15, 4638–4653 (2025). https://doi.org/10.1007/s13346-025-01846-4 Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s13346-025-01846-4