Biomimicking Trilayer Scaffolds with Controlled Estradiol Release for
Uterine Tissue Regeneration
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 ℃. The
developed trilayer tissue engineering scaffolds would provide a new
insight for uterine tissue regeneration.