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

Abstract

Tissue engineering has emerged as a new approach with the potential to overcome the limitations of traditional therapies. The objective of this study was to test whether our polymeric scaffold is able to resist the corrosive action of bile and to support a cell's infiltration and neoangiogenesis with the aim of using it as a biodegradable tissue substitute for serious bile duct injuries. In particular, a resorbable electrospun polyhydroxyethylaspartamideepolylactic acid (90 mol% PHEA, 10 mol% PLA)/polycaprolactone (50:50 w/w) plate scaffold was implanted into rabbit gallbladder to assess the in vivo effects of the lytic action of the bile on the scaffold structure and then as a tubular scaffold to create a biliarydigestive anastomosis as well. For the above evaluation, 5 animals were used and killed after 15 days and 5 animals after 3 months. At 15-day and 3-month follow-ups, the fibrillar structure was not digested by lytic action bile. The fibers of the scaffold were organized despite being in contact with bile action. A new epithelial tissue appeared on the scaffold surface suggesting the suitability of this scaffold for future studies of the repair of biliary tract injuries with the use of resorbable copolymer on biliary injuries. E XTRAHEPATIC biliary tract lesions occurring during laparoscopic cholecystectomy are burdened by perioperative morbidity and mortality [1,2], reduction of longterm survival [3], and reduction of the patient's quality of life [4,5]. Although the incidence of biliary injury during laparotomy is 0.1%e0.2% [6], in the case of the laparoscopic approach it becomes w2-fold or even 3-fold higher [7].Various attempts have been made to reconstruct the bile duct with the use of nonabsorbable vascular grafts, such as expanded polytetrafluoroethylene, with unsatisfactory results due to a high rate of stenosis, early-occurring infections, and long-term foreign body reactions [8e12]. Autologous grafts have been proposed as possible prosthetic material, but they showed extremely low results in the long term [13e16].Rosen et al [17] described a method of biliary tree regeneration using the porcine small intestinal submucosa, another alternate material that does not involve any foreign body reaction but is burdened by the risk of zoonoses and abnormal wound healing [18,19].At present the criterion-standard surgical option is the creation of derivative biliary-digestive anastomoses: nevertheless, this kind of intervention does not restore a complete physiologic anatomy and is burdened by a high rate of morbidity and mortality with a consequent reduction in the patient's quality of life. The approach of regenerative medicine could be the most simple and effective solution for the repair of iatrogenic lesions of the biliary tract [20e23]. The tissue engineering approach requires the use of biodegradable scaffolds to allow cell recruitment from the Funding: PRIN 2015: "Chirurgia rigenerativa nei difetti della parete addominale e nel deficit congenito o acquisito delle vie escretrici urinarie, b...

Liver Tissue Engineering: Challenges and Opportunities

“…Lee et al. and Auth et al demonstrated the formation of the efficient hepato-biliary network under coculture conditions (hepatocytes and cholangiocytes). , In addition, a number of tissue-engineered artificial bile ducts have been reported. − However, integration of bile network and its incorporation in the 3D implantable constructs still remains less explored. In this regard, the whole liver decellularized matrix has gained importance because of retention of the intact biliary network .…”

PDAC-on-chip for in vitro modeling of stromal and pancreatic cancer cell crosstalk

“…These results underline the importance of a biomimetic substrate like the electrospun PCL/gel nanofibrous matrix in promoting the epithelial cell viability and functionality, as widely discussed in literature. [86][87][88][89][90] The co-culture conditions implemented in our model have allowed us to preliminarily evaluate the reciprocal influence that the HPDE-KRAS cells and the PSCs have on each other. Specifically, we observed from the confocal images the morphological changes in stellate cells that appear in a spindle shape, indicating their activation as highlighted in the study of Lee and coworkers.…”

Regenerative medicine for the hepatobiliary system: A review

“…Acellular tubular constructs were developed using multiple materials such as polylactic acid (PLA), polycaprolactone (PCL), and polyglycolic acid (PGA). 113,[115][116][117][118][119][120][121][122] Those scaffolds were designed to be completely absorbable and have proven to be replaced by a healthy, epithelized, and vascularized wall indistinguishable from the native CBD. 113,118 Despite promising results from the use of acellular tubes in animals, all studies were performed in healthy animals.…”