The Fabrication Of Dual-Layer And Induced-Cell-Laden Biliary Scaffold And The Application In Bile Duct Regeneration

Bile duct injury is a common complication of hepatobiliary surgeries on clinical practice with poorly satisfactory curative effect.Implanting artificial tubular scaffold,especially manufactured though methods of tissue engineering,for supporting and replacing defected native bile duct is an important option of treatments for bile duct injury.Here,we selected biomaterials with ideal mechanical properties and outstanding biological compatibility,and fabricated a novel dual-layer gelatin methacrylate(Gel MA)/ poly(ethylene glycol)diacrylate(PEGDA)-poly(lactic-co-glycolic acid)(PLGA)tubular scaffold laden with induced bone marrow-derived mesenchymal stem cells(bMSC)for bile duct regeneration.The inner layer of PLGA offered adequate mechanical strength for the scaffold,and the outer layer of Gel MA/PEGDA provided excellent biocompatibility and conditions to bMSC cells for living and induced differentiation.Moreover,in the functional assays,cholic acid and its derivants were convinced inducing bMSC-cholangiocyte differentiation in culture,and could also affect bMSC cells transforming to cholangiocyte-like cells in hydrogels.Then,in the experiment in vivo,induced-bMSC-laden Gel MA/PEGDA-PLGA and blank PLGA scaffolds were transplanted into animal models for assessing the repair of bile duct injury.The results showed that after 3 months,induced-bMSC-laden Gel MA/PEGDA-PLGA scaffold enhanced bile duct repairing,promoted biliary epithelium integrating,and elevated vessels and muscle layer regenerating significantly,compared to blank PLGA scaffold.Above all,the dual-layer and induced-cell laden Gel MA/PEGDA-PLGA composite bile duct scaffold with superior biocompatibility and distinct function of inducing differentiation had a remarkable effect on supporting bile duct regeneration.