TY - JOUR
T1 - Peptide Hydrogels - A Tissue Engineering Strategy for the Prevention of Oesophageal Strictures.
AU - Kumar, Deepak
AU - Workman, Victoria Louise
AU - O'Brien, Marie
AU - McLaren, Jane
AU - White, Lisa
AU - Ragunath, Krish
AU - Rose, Felicity
AU - Saiani, Alberto
AU - Gough, Julie
PY - 2017/10/10
Y1 - 2017/10/10
N2 - Endoscopic treatment of Barrett’s oesophagus often leads to further damage of healthy tissue causing fibrotic tissue formation termed as strictures. This study shows that synthetic, self-assembling peptide hydrogels (PeptiGelDesign) support the activity and function of primary oesophageal cells, leading to epithelialisation and stratification during in vitro 3D coculture. Following buffering in culture media, oesophageal stromal fibroblasts (rOSFs) were incorporated into a library of peptide hydrogels, whereas oesophageal epithelial cells (mOECs) were seeded on the surface. Optimal hydrogels (PGD-AlphaProC and PGD-CGD2) supported mOEC viability (>95 %), typical cell morphology (cobblestone-like), and slower migration over a shorter distance compared to a collagen control, at 48 hours. Positive expression of typical epithelial markers (ZO-1 and cytokeratins) was detected using immunocytochemistry at day 3 in culture. Furthermore, optimal hydrogels were identified which supported rOSF viability (> 95%) with homogenous distribution when incorporated into the hydrogels and also promoted the secretion of collagen type I detected using ELISA, at day 7. 3D co-culture model using optimal hydrogels for both cell types supported a stratified epithelial layer (expressing involucrin and AE1/AE3 markers). Findings from this study could lead to the use of peptide hydrogels as a minimally invasive endoscopic therapy to manage oesophageal strictures.
AB - Endoscopic treatment of Barrett’s oesophagus often leads to further damage of healthy tissue causing fibrotic tissue formation termed as strictures. This study shows that synthetic, self-assembling peptide hydrogels (PeptiGelDesign) support the activity and function of primary oesophageal cells, leading to epithelialisation and stratification during in vitro 3D coculture. Following buffering in culture media, oesophageal stromal fibroblasts (rOSFs) were incorporated into a library of peptide hydrogels, whereas oesophageal epithelial cells (mOECs) were seeded on the surface. Optimal hydrogels (PGD-AlphaProC and PGD-CGD2) supported mOEC viability (>95 %), typical cell morphology (cobblestone-like), and slower migration over a shorter distance compared to a collagen control, at 48 hours. Positive expression of typical epithelial markers (ZO-1 and cytokeratins) was detected using immunocytochemistry at day 3 in culture. Furthermore, optimal hydrogels were identified which supported rOSF viability (> 95%) with homogenous distribution when incorporated into the hydrogels and also promoted the secretion of collagen type I detected using ELISA, at day 7. 3D co-culture model using optimal hydrogels for both cell types supported a stratified epithelial layer (expressing involucrin and AE1/AE3 markers). Findings from this study could lead to the use of peptide hydrogels as a minimally invasive endoscopic therapy to manage oesophageal strictures.
U2 - 10.1002/adfm.201702424
DO - 10.1002/adfm.201702424
M3 - Article
SN - 1616-3028
VL - 27
JO - Advanced Functional Materials
JF - Advanced Functional Materials
IS - 38
M1 - 1702424
ER -