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 congenital childhood conditions such as atresia. Previous attempts have not been successful and challenges remain. Small intestine submucosa (SIS) is an acellular matrix material with good biological properties though, as is common with these types of materials, demonstrably poor mechanical properties. In this work, electrospinning was used to mechanically reinforce tubular SIS with poly lactic-co-glycolic acid PLGA nanofibers. It was hypothesised that if attachment could be achieved between the two materials this would (i) improve the SIS mechanical properties, (ii) facilitate smooth muscle cell alignment to support directional growth of muscle cells and (iii) allow for the delivery of bioactive molecules (VEGF in this instance). Through a relatively simple multistage process, adhesion between the layers was achieved without chemically altering the SIS. It was also found that altering mandrel rotation 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. Smooth muscle cells cultured on the aligned fibres showed resultant unidirectional alignment. In vivo the SIS-PLGA scaffolds demonstrated 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, in vivo and good cellular infiltration was observed. 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 acellular matrix materials and electrospun fibres layers offers the potential utility in other applications.

Fabrication of multilayered electrospun poly(lactic‐co‐glycolic acid)/polyvinyl pyrrolidone + poly(ethylene oxide) scaffolds and biocompatibility evaluation

“…Its special attributes include good biocompatibility, excellent mechanical properties, regulatable biodegradability, and electrospinnability. However, due to the poor hydrophilicity of PLGA, its applications in regenerative medicine have been limited 8,9 …”

The effects of bone marrow stem and progenitor cell seeding on urinary bladder tissue regeneration

“…The reduced bladder capacity of SIS grafted animals following bladder augmentation may be attributed to the mechanical features of SIS. Although SIS is a durable, flexible, viscoelastic material and has been utilized successfully for multiple clinical applications 41,[44][45][46][47] , it lacks structural resilience and can undergo significant graft deformation in vivo, especially in situations where graft size is small (0.5 cm × 0.5 cm × 0.01 cm) as in our bladder augmentation model. Other groups have experienced graft contraction utilizing SIS in non-urological settings 40 .…”

A narrative review of esophageal tissue engineering and replacement: where are we?

“…These demonstrated successful replacement by skeletal muscle and epithelium, but SIS and UBS graft tube repair of circumferential defects were plagued by strictures (27). Addition of synthetic polyesters such as PLGA and poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) to SIS have been used in-vitro to improve the mechanical properties with some positive results but have not yet been trialed in animal models (28,29). Cell-seeded SIS will be discussed in the next section.…”