Three-Dimensional Bio-Printed Autologous Omentum Patch Ameliorates Unilateral Ureteral Obstruction-Induced Renal Fibrosis

Recent advances in the field of tissue engineering and regenerative medicine have contributed to the repair of damaged tissues and organs. Renal dysfunctions such as chronic kidney disease (CKD) are considered intractable owing to its cellular heterogeneity. In addition, the absence of definitive treatment options other than dialysis or kidney transplantation in advanced CKD. In this study, we investigated therapeutic effects of a three-dimensional (3D) bio-printed omentum patch as treatment source. Because omentum contains a lot of biological sources for immune regulation and tissue regeneration, it has been used in clinic for >100 years. By using autologous tissue as a bio-ink, the patch could minimize the immune response. The mechanically micronized omentum without any additives became small enough to print, but the original components could be preserved. Then, the 3D printed omentum patch was transplanted under renal subcapsular layer in unilateral ureteral obstruction (UUO) rat model. After 14 days of patch transplantation, the kidneys were analyzed through bulk RNA sequencing and histopathological staining. From the results, decreased tubular injury was observed in the omentum patch group. In addition, the omentum patch significantly altered biological process of gene ontology such as fibrosis-related gene and growth factors. RNA sequencing confirmed the antifibrotic effect by inhibiting fibrosis-inducing mechanisms within PI3K-AKT and JAK-STAT pathways. In conclusion, the omentum patch showed the effect of antitubular injury and antifibrosis on UUO kidneys. In particular, the omentum patch is expected to protect the organ from further degeneration and loss of function by inhibiting the progression of fibrosis. The omentum patch can be a novel therapeutic option for renal dysfunction. Impact statement Many studies and clinical trials are being conducted to develop new treatments for kidney disease. However, there are no newly developed renal replacement therapies. In this study, we developed a new treatment that can ameliorate renal interstitial fibrosis using three-dimensional (3D) bio-printed autologous omentum patch. The 3D printer enables precise patch printing, and the bio-ink made of autologous tissue minimizes the immune response after transplantation. The whole kidneys were analyzed by RNA sequencing and histopathological staining 14 days after transplantation. From the results, the omentum patch had the effect of relieving tubular injury in the injured state. Also, the omentum patch significantly altered biological process of gene ontology. In particular, genes related to fibrosis were observed to be downregulated by the omentum patch. RNA sequencing confirmed that the antifibrotic effect was owing to inducing mechanisms of PI3K-AKT and JAK-STAT pathways. The findings reported in this study represent a significant advancement in the application of 3D bio-printer to damaged organ treatments, especially fibrosis-related diseases.