A novel therapy strategy for bile duct repair using tissue engineering technique: PCL/PLGA bilayered scaffold with hMSCs

Abstract

The current clinical treatments for complications caused by hepatobiliary surgery still have some inevitable weakness. The aim of the study was to fabricate a tissue-engineered bile duct that utilized a novel bilayered polymer scaffold combined with human bone marrow-derived mesenchymal stem cells (hMSCs) for new treatment of biliary disease. The biocompatibility of polycaprolactone (PCL) (PCL)/poly(lactide-co-glycolide) (PLGA) scaffold with hMSCs was first examined, and the hMSC-PCL/PLGA constructs (MPPCs) prepared. The MPPCs and blank scaffolds were then transplanted into 18 pigs for evaluation its efficacy on bile duct repairing, respectively. In vitro, the PCL/PLGA scaffold was verified to support the adhesion, proliferation and matrix deposition of hMSCs. There was no sign of bile duct narrowing and cholestasis in all experimental animals. At 6 months, the MPPCs had a superior repairing effect on the bile duct injury, compared with the blank PCL/PLGA scaffolds. Therefore, the implanted scaffolds could not only support the biliary tract and allow free bile flow but also had direct or indirect positive effects on repair of injured bile duct. Copyright © 2015 John Wiley & Sons, Ltd.

Production and Characterization of an Integrated Multi-Layer 3D Printed PLGA/GelMA Scaffold Aimed for Bile Duct Restoration and Detection

“…The measured tensile modulus of the multi-layer 3D-fabrication of PLGA/GelMA/IKVAV/USPIO scaffold was in the range of 14.05 -20.37 MPa and the compressive modulus in the range of 0.024 -0.04 MPa, which was suitable for bile duct implantation. Previous research also reported that the mechanical strength of the pure PLGA scaffold was similar to a real bile duct (Zong et al, 2017). The mechanical test indicated that the PLGA/GelMA/IKVAV/USPIO 3D conduit has both flexibility and toughness, which provide a supporting structure and allow duct regeneration.…”

“…Among them, poly (L-lactide-co-glycolide) (PLGA) and polycaprolactone (PCL) was a biocompatible (Reid et al, 2013), degradable (Lee et al, 2012), non-toxic material (Li et al, 2015). It has many successful applications in bile duct regeneration (Zong et al, 2017). PLGA could provide sufficient support strength to prevent bile duct contraction and narrowness.…”

“…The second factor is surface modification and scaffold fabrication (Li et al, 2019). Although numerous materials have been exploited for artificial bile ducts, such as gelatin (Yan et al, 2018), poly (L-lactide-co-glycolide) (PLGA) (Zong et al, 2017), and polycaprolactone (PCL) (Bloise et al, 2020), few studies reported bilayered scaffold for bile duct tissue engineering. Li et al (2020) reported a novel 3D printing PCL/GelMA scaffold containing USPIO for MRI, which could achieve MRI imaging and be beneficial to the proliferation of cells on the scaffolds, but there was poor cell adhesion properties.…”

Injectable and Crosslinkable PLGA‐Based Microribbons as 3D Macroporous Stem Cell Niche

“…[ 7,8 ] Furthermore, PLGA scaffolds made using conventional methods generally do not support injectability and are only implantable after fabrication, which makes them unsuitable for minimally invasive delivery. [ 6,9 ] There remains a critical need to develop injectable and in situ crosslinkable PLGA scaffolds that are macroporous and support homogeneous cell encapsulation.…”

Electrospun Polyhydroxyethyl-Aspartamide–Polylactic Acid Scaffold for Biliary Duct Repair: A Preliminary In Vivo Evaluation

“…Some polymeric materials have already been proposed as artificial substitutes of both natural and synthetic bile ducts [25,26]. Zong et al focused on the necessity of the scaffold not only being a passive conduit to allow bile flux, but also potentially supporting cell penetration, adhesion, and differentiation, as well as its degradation within the given time [27].…”