Shangsi Chen,Junzhi Li,Liwu Zheng,Jie Huang,Min Wang
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.
Shangsi Chen,Jiahui Lai,Jizhuo Chen,Liwu Zheng,Min Wang
Surgical resection is an efficient treatment for cancerous tissues and uterine fibroids in the women uterus. However, the insufficiency of clinical interventions could result in tumor recurrence, and the defective tissues remained would cause intrauterine adhesions (IUAs) and further affect reproduction capacity. In this study, 3D printed hydrogel/poly( l -lactide- co -trimethylene carbonate) (PLLA-co-TMC, “PTMC” in short) core/shell scaffolds with NIR-tuned doxorubicin hydrochloride (DOX) and estradiol (E2) dual release were designed and fabricated for cancer therapy and uterine regeneration. Gelatin (Gel) and DOX were homogeneously mixed and then 3D printed to form Gel-DOX scaffolds. Gel-DOX scaffolds were then immersed in PTMC-PDA@E2 solution to fabricate Gel-DOX/PTMC-PDA@E2 core/shell scaffolds. Consequently, Gel-DOX/PTMC-PDA@E2 scaffolds could release DOX and E2 in a chronological manner, firstly delivering DOX assisted by phototherapy (PTT) to effectively kill Hela cells and then sustainably releasing E2 to promote uterine tissue regeneration. In vitro experiments showed that core/shell scaffolds exhibited excellent anticancer efficiency through the synergy of DOX release and hyperthermia ablation. Moreover, E2 could be sustainably released for over 28 days in vitro to promote the proliferation of bone marrow-derived mesenchymal stem cells (BMSCs). The novel Gel-DOX/PTMC-PDA@E2 core/shell scaffolds have therefore exhibited potential promise for the treatment of cancer therapy and uterine regeneration.
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