A potential platform for developing 3D tubular scaffolds for paediatric organ development

Abstract

Children suffer from damaged or loss of hollow organs i.e. trachea, oesophagus or arteries from birth defects or diseases. Generally these organs possess an outer matrix consisting of collagen, elastin, and cells such as smooth muscle cells (SMC) and a luminal layer consisting of endothelial or epithelial cells, whilst presenting a barrier to luminal content. Tissue engineering research enables the construction of such organs and this study explores this possibility with a bioabsorbable nanocomposite biomaterial, polyhedral oligomeric silsesquioxane poly(ε-caprolactone) urea urethane (POSS-PCL).Our established methods of tubular graft extrusion were modified using a porogen-incorporated POSS-PCL and a new lamination method was explored. Porogen (40, 60 or 105 µm) were introduced to POSS-PCL, which were fabricated into a bilayered, dual topography matching the exterior and luminal interior of tubular organs. POSS-PCL with different amounts of porogen were tested for their suitability as a SMC layer by measuring optimal interactions with human adipose derived stem cells. Angiogenesis potential was tested with the chorioallantoic membrane assay. Tensile strength and burst pressures of bilayared tubular grafts were determined. Scaffolds made with 40 µm porogen demonstrated optimal adipose derived stem cell integration and the scaffolds were able to accommodate angiogenesis. Mechanical properties of the grafts confirmed their potential to match the relevant physiological and biophysical parameters. This study presents a platform for the development of hollow organs for transplantation based on POSS-PCL. These bilayered-tubular structures can be tailor-made for cellular integration and match physico-mechanical properties of physiological systems of interest. More specific luminal cell integration and sources of SMC for the external layer could be further explored.

Tubular organ epithelialisation

“… (1) Solvent evaporation of polycaprolactone; (2) magnified cross section of (1); 74 (3) magnified cross section of solvent exchanged polycaprolactone-based scaffold; 74 (4) decellularised tracheal segment; 75 (5) 3D-printed tubular tissue; 76 (6) hybrid scaffold (polyurethane outer coat on a decellularised oesophagus); (7) electrospun tubular tissue. 77 Figure of structures of natural tubular organs is adapted from Basu and Ludlow.…”

Transdifferentiation of human endothelial progenitors into smooth muscle cells

“…Smooth muscle cells (SMC) are non-striated muscle cells found in the walls of blood vessels and hollow organs including bladder, lung, and intestine 1 . They differ from other terminally differentiated cells such as cardiac and skeletal myocytes in that they maintain plasticity in modulating from a contractile to a synthetic phenotype in response to various stimuli 2,3 .…”

Composite Scaffolds Based on Intestinal Extracellular Matrices and Oxidized Polyvinyl Alcohol: A Preliminary Study for a New Regenerative Approach in Short Bowel Syndrome

“…Nevertheless, the isolation of pure stem cells from intestinal crypts is also difficult because of the lack of specific stem cells markers [ 55 ]. Hence, in the present work, we focused on mesenchymal stem cells, in particular Ad-MSCs, which are currently considered an interesting cell source for tissue engineering of epithelium [ 56 ], endothelium [ 57 – 59 ], and smooth muscle, particularly for pediatric applications [ 60 , 61 ]. In Figure 3(a) , the fibroblastoid appearance of Ad-MSCs is shown.…”