SIS/Aligned Fibre Scaffold Designed to Meet Layered Oesophageal Tissue Complexity and Properties

Abstract

With donor organs not readily available the need for a tissue engineered oesophagus remains high particularly for congenial childhood conditions such as atresia. Previous attempts have not been very successful and challenges remain to be overcome. Small intestine submucosa (SIS) is an a cellular matrix material with good biological properties though, as with these materials, demonstrably poor mechanical properties. In this work electrospinning was used to mechanically reinforce a unique tubular SIS with PLGA nanofibers. It was hypothesised that if attachment could be achieved between the two materials than this would (i) improve the SIS's mechanical properties, (ii) facilitate smooth muscle cell alignment to support directional growth of muscle cells and potentially restore contractility and (iii) allow for the delivery of bioactive molecules (VEGF in this instance). Through a multistage process adhesion between the layers was achieved without chemically altering the SIS. It was also found that altering mandrel rotational speed affected the alignment of the PLGA nanofibers.SIS-PLGA scaffolds performed mechanically better than SIS alone; yield stress improvement was 200% and 400% along the longitudinal and circumferential direction, respectively (greatest with highly aligned fibres produced at 5000 rpm). Smooth muscle cells cultured on the aligned fibres showed resultant unidirectional alignment. In vivo the SIS-PLGA scaffolds demonstrated relatively limited foreign body reaction judged by the type and proportion of immune cells present and lack of fibrous encapsulation. The scaffolds remained intact at 4 weeks which is required for a structural tissue engineering matrix and obtained good cellular infiltration. The incorporation of VEGF within SIS-PLGA scaffolds increased the blood vessel density of the surrounding tissues, highlighting the possible stimulation of endothelialisation by angiogenic factor delivery. Overall, the designed SIS-PLGA-VEGF hybrid scaffolds might be used as a potential matrix platform for oesophageal tissue engineering. In addition to this, achieving improved attachment between layers of a cellular matrix materials and electrospun fibres layers does possess the potential to be applied to other applications.