Restoration of pregnancy function using GT/PCL biofilm in a rabbit model of uterine injury.

Biomaterial scaffolds have been used successfully to promote the regenerative repair of small endometrial lesions in small rodents, providing partial restoration of gestational function. The use of rabbits in this study allowed us to investigate a larger endometrial tissue defect and myometrial-injury model. A gelatin/polycaprolactone (GT/PCL) gradient-layer biofilm was sutured at the defect to guide the reconstruction of the original tissue structure. 28 days post-implantation, the uterine cavity had been restored its original morphology; endometrial growth was accompanied by the formation of glands and blood vessels, and the fragmented myofibers of the uterine smooth muscle had begun to resemble the normal structure of the lagomorph uterine cavity, arranging in a circular luminal pattern and a longitudinal serosal pattern. In addition, the repair site supported both embryonic implantation into the placenta and normal embryonic development. 4D label-free proteomic analysis identified the cell adhesion molecules (CAMs), phagosome, ferroptosis, rap1 signaling pathways, hematopoietic cell lineage, complement and coagulation cascades, tricarboxylic acid (TCA) cycle, carbon metabolism, and HIF-1 signaling pathways as important in the endogenous repair process of uterine-tissue injury, and acetylation of protein modification sites upregulated these signaling pathways.