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. Twenty-eight days postimplantation, the uterine cavity had been restored to 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. Four-dimensional label-free proteomic analysis identified the cell adhesion molecules, phagosome, ferroptosis, rap1 signaling pathways, hematopoietic cell lineage, complement and coagulation cascades, tricarboxylic acid cycle, carbon metabolism, and hypoxia inducible factor (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.
Impact Statement
Current tissue engineering and regenerative medicine strategies utilize advanced biomaterials to assist in the treatment of tissue injury to achieve good repair outcomes. At present, there are few studies that investigate the mechanism that determines how biomaterial scaffolds guide endogenous regeneration and repair of uterine tissue. This study is the first to investigate how 3D electrospun gelatin/polycaprolactone (GT/PCL) biofilms can be used to repair large endometrial and myometrial injuries and to use proteomics to explore endogenous repair mechanisms that may be activated during biofilm-guided tissue repair. This study provides a theoretical basis for further research on the endogenous regeneration and repair mechanism of the uterus.
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