A 3D bioinspired highly porous polymeric scaffolding system forin vitrosimulation of pancreatic ductal adenocarcinoma

Abstract

A 3D biomimetic model for in vitro studies of pancreatic cancer.

Chemoradiotherapy screening in a novel biomimetic polymer based pancreatic cancer model

“…The scaffolds were fabricated via the thermal induced phase separation method prepared as reported previously. 7,[62][63][64] Briey, PU beads (Noveon, Belgium) were dissolved in dioxane (5% w/v) (99.8% anhydrous pure, Sigma-Aldrich, UK) followed by quenching at À80 C for 3 h. The solvent was then removed by freeze drying in a poly-ethylene glycol (PEG) bath at À15 C under 0.01 mbar vacuum pressure. The scaffolds were then cut into 5 Â 5 Â 5 mm 3 cubes and sterilised by exposing them to 70% ethanol (3 h) and UV ray (1 h).…”

“…6 More specically, the socalled tumour microenvironment (TME), which is a cocktail of biochemical, cellular, biomechanical and structural components has been shown to affect the efficiency of treatment delivery to the tumour. 4,[7][8][9] Traditionally, PDAC research including treatment screening, is conducted in (a) 2D in vitro systems [10][11][12][13] (tissue culture asks or Petri-plates) or in (b) animals, mainly mice. 10,11,[14][15][16][17][18] Generally, 2D in vitro cultures are responsive to radiotherapy and chemotherapy, reproducible and very easy to use.…”

“…2,10,14,15,[23][24][25][26][27] However, they are expensive, difficult to reproduce and complex to use. 4,7,21,23,26,28 Additionally, there is evidence that animal models undergo signicant genetic changes that diverge from the evolutionary course observed in human disease, raising concerns about the models' translatability and application for personalised therapies. 2 More recently, 3D in vitro models have emerged and are being developed as low cost, promising alternatives to animals.…”

“…2 More recently, 3D in vitro models have emerged and are being developed as low cost, promising alternatives to animals. 7,[29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] However, most studies focus on the development of the actual 3D model and, to the best of our knowledge, there are very limited 3D studies on PDAC treatment screening (chemotherapy and radiotherapy) with most studies conducted in 3D spheroids (cell aggregates). 14,32,[34][35][36][49][50][51][52] Generally, these studies report a higher resistance of PDAC to treatment in 3D when compared to 2D cultures, a trend which is in closer alignment with in vivo studies.…”

Hole-closing model reveals exponents for nonlinear degenerate diffusivity functions in cell biology

“…In this particular example, the initial wound is circular in shape; however, a feature of our experimental design is that we are able to make the initial wounds any shape we choose. More generally, the study of hole-closing problems in cell biology has applications to a range of experimental wound healing scenarios, such as the circular wounds created by barrier assays [28][29][30], in a mammal's ear [31] or cornea [32,33] or a human skin equivalent construct [34], for example; similar mechanisms and geometry are involved in cell bridging experiments in tissue engineering [35]. Further motivation for our study arises from the lack of consensus when using (1) to model cell migration on the appropriate choice of the diffusion exponent n; we aim to shed light on this issue.…”