posted on 2024-01-31, 19:34authored byShangsi Chen, Shenglong Tan, Liwu Zheng, Min Wang
Owing to dysfunction of the uterus,
millions of couples around
the world suffer from infertility. Different from conventional treatments,
tissue engineering provides a new and promising approach to deal with
difficult problems such as human tissue or organ failure. Adopting
scaffold-based tissue engineering, three-dimensional (3D) porous scaffolds
in combination with stem cells and appropriate biomolecules may be
constructed for uterine tissue regeneration. In this study, a hierarchical
tissue engineering scaffold, which mimicked the uterine tissue structure
and functions, was designed, and the biomimicking scaffolds were then
successfully fabricated using solvent casting, layer-by-layer assembly,
and 3D bioprinting techniques. For the multilayered, hierarchical
structured scaffolds, poly(l-lactide-co-trimethylene
carbonate) (PLLA-co-TMC, “PLATMC” in
short) and poly(lactic acid-co-glycolic acid) (PLGA)
blends were first used to fabricate the shape-morphing layer of the
scaffolds, which was to mimic the function of myometrium in uterine
tissue. The PLATMC/PLGA polymer blend scaffolds were highly stretchable.
Subsequently, after etching of the PLATMC/PLGA surface and employing
estradiol (E2), polydopamine (PDA), and hyaluronic acid (HA), PDA@E2/HA
multilayer films were formed on PLATMC/PLGA scaffolds to build an
intelligent delivery platform to enable controlled and sustained release
of E2. The PDA@E2/HA multilayer films also improved the biological
performance of the scaffold. Finally, a layer of bone marrow-derived
mesenchymal stem cell (BMSC)-laden hydrogel [which was a blend of
gelatin methacryloyl (GelMA) and gelatin (Gel)] was 3D printed on
the PDA@E2/HA multilayer films of the scaffold, thereby completing
the construction of the hierarchical scaffold. BMSCs in the GelMA/Gel
hydrogel layer exhibited excellent cell viability and could spread
and be released eventually upon biodegradation of the GelMA/Gel hydrogel.
It was shown that the hierarchically structured scaffolds could evolve
from the initial flat shape into the tubular structure completely
in an aqueous environment at 37 °C, fulfilling the requirement
for curved scaffolds for uterine tissue engineering. The biomimicking
scaffolds with a hierarchical structure and curved shape, high stretchability,
and controlled and sustained E2 release appear to be very promising
for uterine tissue regeneration.