Kim Soo-Rim, Lee Hwa-Yong
Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Republic of Korea.
Department of Molecular Medicine, School of Medicine, Gachon University, Incheon 406-840, Republic of Korea.
Theranostics. 2026 Jan 1;16(2):736-775. doi: 10.7150/thno.123298. eCollection 2026.
Endometrial regeneration remains a significant clinical challenge for women with intrauterine adhesions (IUAs), thin endometrium, or uterine factor infertility, conditions that severely impair fertility and reproductive outcomes. Traditional hormonal and surgical interventions often fail to restore the structural and functional integrity of damaged endometrial tissue. This review comprehensively examines integrative bioengineering strategies for endometrial regeneration, focusing on the synergistic applications of biomaterials, stem cells, organoids, and organ-on-a-chip technologies. Natural polymers such as collagen, gelatin, alginate, hyaluronic acid, and synthetic polymers including PCL, PLA, PGA, and PLGA have been comprehensively evaluated for their ability to mimic extracellular matrix, support cell proliferation, angiogenesis, and modulate immune responses. The incorporation of mesenchymal stem cells, extracellular vesicles, and growth factors into bioengineered scaffolds, such as hydrogels and nanofiber membranes, enhances regenerative efficacy. Furthermore, emerging platforms, such as endometrial organoids, 3D bioprinting, and organ-on-a-chip systems, offer physiologically relevant models for precision regenerative medicine. Innovations such as AI-assisted monitoring, 4D printing, and advanced drug delivery systems represent transformative approaches to overcome current therapeutic limitations. This review highlights the convergence of materials science, stem cell biology, and microengineering as a foundation for next-generation, personalized therapies aimed at restoring endometrial function and fertility. In addition, the review highlights biomaterial-based strategies as the foundation of endometrial regeneration, by detailing how natural polymers (e.g., collagen, gelatin, alginate, hyaluronic acid) and synthetic polymers (e.g., PCL, PLA, PLGA) support tissue repair structurally and by mediating biological functions. The integration of advanced technologies, such as 4D printing, AI-assisted monitoring, and stem cell-derived extracellular vesicle delivery has emerged as a transformative direction for overcoming current clinical challenges. Collectively, these approaches offer a next-generation therapeutic paradigm for restoring endometrial function and fertility.
对于患有宫腔粘连（IUA）、子宫内膜薄或子宫因素不孕症的女性而言，子宫内膜再生仍是一项重大的临床挑战，这些病症会严重损害生育能力和生殖结局。传统的激素和手术干预往往无法恢复受损子宫内膜组织的结构和功能完整性。本综述全面研究了用于子宫内膜再生的整合生物工程策略，重点关注生物材料、干细胞、类器官和芯片器官技术的协同应用。已对天然聚合物如胶原蛋白、明胶、藻酸盐、透明质酸，以及合成聚合物如聚己内酯（PCL）、聚乳酸（PLA）、聚乙醇酸（PGA）和聚乳酸-羟基乙酸共聚物（PLGA）进行了全面评估，以考察它们模拟细胞外基质、支持细胞增殖、血管生成和调节免疫反应的能力。将间充质干细胞、细胞外囊泡和生长因子整合到生物工程支架（如水凝胶和纳米纤维膜）中，可提高再生效果。此外，新兴平台，如子宫内膜类器官、3D生物打印和芯片器官系统，为精准再生医学提供了生理相关模型。人工智能辅助监测、4D打印和先进药物递送系统等创新代表了克服当前治疗局限性的变革性方法。本综述强调了材料科学、干细胞生物学和微工程的融合，作为旨在恢复子宫内膜功能和生育能力的下一代个性化疗法的基础。此外，该综述强调了基于生物材料的策略作为子宫内膜再生的基础，详细阐述了天然聚合物（如胶原蛋白、明胶、藻酸盐、透明质酸）和合成聚合物（如PCL、PLA、PLGA）如何在结构上支持组织修复并介导生物学功能。4D打印、人工智能辅助监测和干细胞衍生细胞外囊泡递送等先进技术的整合已成为克服当前临床挑战的变革性方向。总体而言，这些方法为恢复子宫内膜功能和生育能力提供了下一代治疗模式。
