Melt-electrowritten gelatin-functionalized PCL scaffolds loaded with human umbilical cord mesenchymal stem cells for intrauterine adhesions treatment

Intrauterine adhesion (IUA) is a common refractory gynecological disease characterized by endometrial fibrosis and cavity obliteration that often leads to infertility. In this study, we developed a tissue-engineered construct combining 3D printed PCL scaffolds, surface gelatin conjugation and human umbilical cord mesenchymal stem cells (hUCMSCs) for IUA treatment. PCL scaffolds were fabricated by melt electrowriting (MEW) and subjected to sequential surface modification: NaOH hydrolysis (PCL-N), gelatin coating (PCL-NG), and 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide (EDC/NHS) crosslinking (PCL-NGE). Physicochemical characterization confirmed the successful surface modification. In vitro cytocompatibility was assessed using Cell Counting Kit-8 (CCK-8) assay, live/dead staining, and cytoskeleton staining. The results demonstrated that the PCL-NGE scaffold exhibited superior cytocompatibility toward hUCMSCs, significantly promoting their metabolic activity, adhesion, and spreading. The PCL-NGE-hUCMSCs constructs were then implanted into a rat IUA model, and the histopathological assessment revealed that the PCL-NGE-hUCMSCs group markedly restored endometrial thickness, increased glandular density, and substantially reduced collagen deposition and fibrosis compared to the IUA model group. These findings suggest that gelatin-functionalized PCL scaffolds fabricated using MEW and loaded with hUCMSCs may represent a potential strategy for endometrial regeneration and IUA treatment.