Engineered Full Thickness Electrospun Scaffold for Esophageal Tissue Regeneration: From In Vitro to In Vivo Approach.

Silvia Pisani,Stefania Croce,Marco Benazzo,Simone Mauramati,Lorenzo Cobianchi,Marta Marmonti,Irene Herman,Ida Genta,Rossella Dorati,Maria Antonietta Avanzini,Bice Conti

doi:10.3390/pharmaceutics14020252

Abstract

Acquired congenital esophageal malformations, such as malignant esophageal cancer, require esophagectomy resulting in full thickness resection, which cannot be left untreated. The proposed approach is a polymeric full-thickness scaffold engineered with mesenchymal stem cells (MSCs) to promote and speed up the regeneration process, ensuring adequate support and esophageal tissue reconstruction and avoiding the use of autologous conduits. Copolymers poly-L-lactide-co-poly-ε-caprolactone (PLA-PCL) 70:30 and 85:15 ratio were chosen to prepare electrospun tubular scaffolds. Electrospinning apparatus equipped with two different types of tubular mandrels: cylindrical (∅ 10 mm) and asymmetrical (∅ 10 mm and ∅ 8 mm) were used. Tubular scaffolds underwent morphological, mechanical (uniaxial tensile stress) and biological (MTT and Dapi staining) characterization. Asymmetric tubular geometry resulted in the best properties and was selected for in vivo surgical implantation. Anesthetized pigs underwent full thickness circumferential resection of the mid-lower thoracic esophagus, followed by implantation of the asymmetric scaffold. Preliminary in vivo results demonstrated that detached stitch suture achieved better results in terms of animal welfare and scaffold integration; thus, it is to be preferred to continuous suture.

Highlights

Congenital esophageal malformations, such as atresia, and acquired ones, such as chronic gastroesophageal reflux, Barrett’s esophagus, and strictures, often require surgical intervention and esophageal reconstruction [1]
Esophagectomy is a very invasive surgery that could induce an intense systemic inflammatory response (SIR), stimulating the release of proinflammatory cytokines, which may increase postsurgical risk of cancer recurrence [3]. Another serious possible surgical complication after esophagectomy is postoperative pneumonia, which has been a major cause of hospital mortality [4]
Esophageal surgery is associated with a mortality rate that can reach 13% at 90 days, and esophagectomy, which usually includes lymphadenectomy, remains the treatment of choice for esophageal malignancy

Summary

Introduction

Congenital esophageal malformations, such as atresia, and acquired ones, such as chronic gastroesophageal reflux, Barrett’s esophagus, and strictures, often require surgical intervention and esophageal reconstruction [1]. EMR has become an accepted treatment for early-stage esophageal cancer and high-grade dysplasia associated with Barrett’s esophagus. Esophagectomy is a very invasive surgery that could induce an intense systemic inflammatory response (SIR), stimulating the release of proinflammatory cytokines, which may increase postsurgical risk of cancer recurrence [3]. Another serious possible surgical complication after esophagectomy is postoperative pneumonia (whose frequency is reported to be 7.6–35.9%), which has been a major cause of hospital mortality (for about 2.7–8.7%) [4]. Engineering artificial esophageal scaffolds similar to native esophagus are emerging alternatives that are able to permit bolus and liquids transit, possess mechanical characteristics suitable to withstand leak or rupture

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