Peptide hydrogels — a tissue engineering strategy for the prevention of oesophageal strictures

Kumar, Deepak; Workman, Victoria; O'Brien, Marie Claire; McLaren, Jane S.; White, Lisa J.; Ragunath, Krish; Saiani, Alberto; Gough, Julie; Rose, Felicity R.A.J.

Abstract

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 co-culture. 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), a migration rate of 17.4 μm/hr and a migration distance of 364 μm, at 48 hours. Positive expression of typical epithelial markers (ZO-1 and cytokeratins) was witnessed 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.

Citation

Kumar, D., Workman, V., O'Brien, M. C., McLaren, J. S., White, L. J., Ragunath, K., …Rose, F. R. (2017). Peptide hydrogels — a tissue engineering strategy for the prevention of oesophageal strictures. Advanced Functional Materials, 27(38), Article 1702424. https://doi.org/10.1002/adfm.201702424

• Journal Article Type: Article
• Acceptance Date: Jul 11, 2017
• Online Publication Date: Aug 21, 2017
• Publication Date: Oct 12, 2017
• Deposit Date: Sep 8, 2017
• Publicly Available Date: Sep 8, 2017
• Journal: Advanced Functional Materials
• Print ISSN: 1616-301X
• Electronic ISSN: 1616-3028
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 27
• Issue: 38
• Article Number: 1702424
• DOI: https://doi.org/10.1002/adfm.201702424
• Keywords: Barrett's oesophagus; co-culture model; stiffness; synthetic peptide hydrogels
• Public URL: https://nottingham-repository.worktribe.com/output/887606
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1002/adfm.201702424/full
• Additional Information: This is the peer reviewed version of the following article: D. Kumar, V. L. Workman, M. O'Brien, J. McLaren, L. White, K. Ragunath, F. Rose, A. Saiani, J. E. Gough, Adv. Funct. Mater. 2017, 1702424, which has been published in final form at http://dx.doi.org/10.1002/adfm.201702424. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
• Contract Date: Sep 8, 2017