Decellularized material as scaffolds for tissue engineering studies in long gap esophageal atresia

ABSTRACT

Introduction: Esophageal atresia refers to an anomaly in foetal development in which the esophagus terminates in a blind end. Whilst surgical correction is achievable in most patients, when a long gap is present it still represents a major challenge associated with higher morbidity and mortality. In this context, tissue engineering could represent a successful alternative to restore oesophageal function and structure. Naturally derived biomaterials made of decellularized tissues retain native extracellular matrix architecture and composition, providing a suitable bed for the anchorage and growth of relevant cell types.

Areas covered: This review outlines the various strategies and challenges in esophageal tissue engineering, highlighting the evolution of ideas in the development of decellularized scaffolds for clinical use. It explores the interplay between clinical needs, ethical dilemmas, and manufacturing challenges in the development of a tissue engineered decellularized scaffold for oesophageal atresia.

Expert opinion: Current progress on oesophageal tissue engineering has enabled effective repair of patch defects, whilst the development of a full circumferential construct remains a challenge. Despite the different approaches available and the improvements achieved, a gold standard for fully functional tissue engineered oesophageal constructs has not been defined yet.

Article highlights

• Esophageal atresia is a congenital anomaly in which the continuity of the esophagus is interrupted and a fistula often connects the esophagus to the trachea.

• Whilst less severe cases can be successfully corrected through surgery, long gap atresia (LGOA) is often associated with low successful rate and high risk of long-term complications. Optimal treatment has not been established.

• Tissue engineering could represent a better treatment option for patients with LGOA. Synthetic and hybrid scaffolds have been attempted, with variable suboptimal results.

• Decellularised esophageal scaffolds are now considered a better option because: 1) preservation of esophageal extracellular matrix mimics the 3D structure of the native organ and stimulates cell repopulation in vivo; 2) removal of cell content reduces the risk of rejection and prevents the need of life long immunosuppression and 3) natural constructs can ‘grow’ with the patient through childhood, avoiding the need of multiple surgical interventions.

• Challenges in decellularised esophageal scaffolds production include the need to identify the best tissue source and optimal decellularisation protocol, develop and maintain a tubular patent structure, repopulate the scaffolds in its different layers, stimulate revascularisation, promote structural and functional integration with the host.This box summarizes key points contained in the article.

Declaration of interest

P De Coppi is a National Institute for Health Research Professor. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

P De Coppi is supported by the Great Ormond Street Hospital Charity, the MRC, the Wellcome Trust and the OAK Foundation.