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

Abstract

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.

Multi-stage bioengineering of a layered oesophagus with in vitro expanded muscle and epithelial adult progenitors

“…In addition, organised and functional scaffold re-population in vitro before transplantation maximizes both the ingrowth of neighbouring host cells and angiogenesis 22 – 24 . Finally, while previous studies focused on the cervical oesophagus, which is mainly skeletal 17 , 19 – 22 , thoracic oesophagus is almost exclusively smooth muscle 2 – 6 , 16 . Due to these limitations, all previous attempts failed to provide an optimal approach in the use of decellularized scaffolds as suitable oesophageal substitutes 16 .…”

“…So far, engineered tissues have been successfully applied clinically using decellularized scaffolds to regenerate children’s airway 7 , and encouraging preclinical data have been obtained for engineering of more complex organs such as gut 8 , skeletal muscle 9 – 11 , liver 12 , 13 and lung 14 , 15 . Decellularized scaffolds preserve native extracellular-matrix (ECM) overall architecture and composition acting as natural templates guiding cell anchorage, migration, growth and 3D organization in vivo 2 – 5 , 16 . Acellular matrices have been previously used as oesophageal substitutes, with successful outcomes only when applied as patches for repairing small defects 17 – 19 or as tubular devices replacing only mucosa following endoscopic resection 20 .…”

“…First, the oesophagus is multi-layered so requires engineering of all structural compartments for its reconstruction. Transplanting of appropriate cells appears to be key to promote fast, complete and functional regeneration 4 , 16 , 21 . In addition, organised and functional scaffold re-population in vitro before transplantation maximizes both the ingrowth of neighbouring host cells and angiogenesis 22 – 24 .…”

Role of Bioreactor Technology in Tissue Engineering for Clinical Use and Therapeutic Target Design

“…), has the aim of aiding cell survival, function, and proliferation whilst concomitantly minimising immune responses, which is especially important for tissues to be used in clinical applications, such as heart valves. These scaffolds have been widely reviewed elsewhere [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ], including their use with bioreactor technology. Typically, they are porous to increase cell/scaffold area and promote 3-dimensional growth of the seeded cells.…”

Engineering transplantable jejunal mucosal grafts using primary patient-derived organoids from children with intestinal failure

“…hISCs could be delivered using biodegradable materials such as polyglycolic acid/poly-L-lactic acid polymers 31-33 , however the lack of fine microarchitectural details as well as biological cues responsible for cell engraftment and self-organisation have so far largely limited their translation. On the other hand, biological extracellular matrix (ECM) obtained from decellularization of native organs represent a more physiological alternative to synthetic scaffolds 7,10,34,35 .…”