4 Conclusions
In the current study, a trilayer tissue engineering scaffold mimicking the hierarchical structure of native uterine tissue was designed and trilayer scaffolds of this design were successfully constructed through 4D printing, electrospinning and 3D bioprinting. The trilayer scaffolds had three distinct layers: 3D printed PTMC/TPU scaffold outlayer with shape morphing ability and high stretchability, electrospun PLGA/GelMA-PDA@E2 fibrous interlayer with photothermal effect and controlled and sustained E2 release, and BMSC-laden hydrogel innerlayer providing abundant stem cells at the repair/tissue regeneration site. These trilayer scaffolds were highly stretchable and exhibited comparable mechanical properties with native uterine tissue. Additionally, they could deliver E2 controllably and sustainably. The E2 release from trilayer scaffolds was also pH-responsive and could be tuned by NIR laser irradiation. PLGA/GelMA-PDA@E2 fibers fabricated on the PTMC/TPU scaffold made the scaffold surface more hydrophilic and improved biological performance. BMSCs encapsulated in GelMA/Gel bioinks exhibited high survival rates in the 3D bioprinted hydrogel layer of the trilayer scaffolds. Importantly, the biomimicking trilayer scaffolds had the shape morphing ability, transforming from the planar shape to curved or tubular structures when immersed in the culture medium at 37 ℃. The biomimicking trilayer tissue engineering scaffolds designed and fabricated in the current study have the high potential for uterine tissue regeneration.