4D-printed fibre-reinforced scaffolds with high elasticity and sustained estradiol release for uterine tissue regeneration

Uterine defects caused by diseases and injuries significantly deteriorate the functions of the uterus and even result in infertility. Tissue engineering scaffolds, possessing comparable mechanical strength and sustained estradiol (E2) release and shape-morphing ability to match the anatomical structure of native uterine tissues, may be effective for treating uterine defects and restoring fertility. In the current study, fibre-reinforced scaffolds were fabricated via electrospinning and 4D printing. Short electrospun thermoplastic polyurethane (TPU) fibres encapsulated with polydopamine (PDA) particles (TPU-PDA fibres) were homogenised in poly(L-lactide-co-trimethylene carbonate) (PLLA-co-TMC, ‘PLATMC’ in short) solutions to engineer fibre-reinforced scaffolds via 4D printing. E2 was loaded in PDA particles. The incorporation of TPU-PDA fibres in the PLATMC solution increased the printability of inks and improved the fidelity of printed scaffolds. Moreover, electrospun TPU-PDA fibres reinforced the mechanical strength of printed scaffolds (>2.5 MPa), and fibre-reinforced scaffolds thus prepared were highly elastic (>600% strain). Also, fibre-reinforced scaffolds exhibited sustained E2 release over 8 weeks, which promoted the growth and proliferation of rat bone marrow-derived mesenchymal stem cells (BMSCs). After programmed shape deformation, fibre-reinforced scaffolds could evolve shape morphing through transforming planar shape into a curved or tubular structure to meet the curvature of uterine tissues after being cultured in a culture medium at 37°C, which provides new insight into uterine regeneration.