Biomimicking trilayer scaffolds with controlled estradiol release for uterine tissue regeneration

Shangsi Chen, Junzhi Li, Liwu Zheng, Jie Huang, Min Wang
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Abstract

Scaffold-based tissue engineering provides an efficient approach for repairing uterine tissue defects and restoring fertility. In the current study, a novel trilayer tissue engineering scaffold with high similarity to the uterine tissue in structure was designed and fabricated via 4D printing, electrospinning and 3D bioprinting for uterine regeneration. Highly stretchable poly(l-lactide-co-trimethylene carbonate) (PLLA-co-TMC, “PTMC” in short)/thermoplastic polyurethane (TPU) polymer blend scaffolds were firstly made via 4D printing. To improve the biocompatibility, porous poly(lactic acid-co-glycolic acid) (PLGA)/gelatin methacryloyl (GelMA) fibers incorporated with polydopamine (PDA) particles were produced on PTMC/TPU scaffolds via electrospinning. Importantly, estradiol (E2) was encapsulated in PDA particles. The bilayer scaffolds thus produced could provide controlled and sustained release of E2. Subsequently, bone marrow derived mesenchymal stem cells (BMSCs) were mixed with gelatin methacryloyl (GelMA)-based inks and the formulated bioinks were used to fabricate a cell-laden hydrogel layer on the bilayer scaffolds via 3D bioprinting, forming ultimately biomimicking trilayer scaffolds for uterine tissue regeneration. The trilayer tissue engineering scaffolds thus formed exhibited a shape morphing ability by transforming from the planar shape to tubular structures when immersed in the culture medium at 37°C. The trilayer tissue engineering scaffolds under development would provide new insights for uterine tissue regeneration.

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可控雌二醇释放的仿生三层支架用于子宫组织再生
基于支架的组织工程学为修复子宫组织缺损和恢复生育能力提供了一种有效的方法。本研究设计了一种新型三层组织工程支架,其结构与子宫组织高度相似,并通过 4D 打印、电纺丝和三维生物打印技术制造了这种支架,用于子宫再生。首先通过 4D 打印制作了高伸展性的聚乳酸-三亚甲基碳酸酯(PLLA-co-TMC,简称 "PTMC")/热塑性聚氨酯(TPU)聚合物共混支架。为了提高生物相容性,通过电纺丝在 PTMC/TPU 支架上制成了含有聚多巴胺(PDA)颗粒的多孔聚(乳酸-共聚乙醇酸)(PLGA)/甲基丙烯酰明胶(GelMA)纤维。重要的是,雌二醇(E2)被包裹在 PDA 颗粒中。由此制成的双层支架可控制并持续释放 E2。随后,将骨髓间充质干细胞(BMSCs)与明胶甲基丙烯酰(GelMA)基油墨混合,并通过三维生物打印技术在双层支架上制造细胞水凝胶层,最终形成用于子宫组织再生的仿生物三层支架。由此形成的三层组织工程支架具有形状变形能力,当浸泡在 37°C 的培养基中时,可从平面形状转变为管状结构。正在开发的三层组织工程支架将为子宫组织再生提供新的见解。
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Issue Information Back Cover: High-yield upcycling of feather wastes into solid-state ultra-long phosphorescence carbon dots for advanced anticounterfeiting and information encryption (EXP2 6/2024) Frontispiece: Advancements and challenges in brain cancer therapeutics (EXP2 6/2024) Front Cover: Piezoelectric stimulation enhances bone regeneration in alveolar bone defects through metabolic reprogramming of macrophages (EXP2 6/2024) Pioneering Exploration for a lasting and sustainable future
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