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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.

Authors

Deepak Kumar deepak.kumar@manchester.ac.uk

Victoria Workman v.workman@manchester.ac.uk

Marie Claire O'Brien marie.obrien@manchester.ac.uk

Jane S. McLaren Jane.McLaren@nottingham.ac.uk

Lisa J. White lisa.white@nottingham.ac.uk

Krish Ragunath K.Ragunath@nottingham.ac.uk

Alberto Saiani a.saiani@manchester.ac.uk

Julie Gough j.gough@manchester.ac.uk

Felicity R.A.J. Rose felicity.rose@nottingham.ac.uk



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.

Journal Article Type Article
Publication Date Oct 12, 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
APA6 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), https://doi.org/10.1002/adfm.201702424
DOI https://doi.org/10.1002/adfm.201702424
Keywords Barrett's oesophagus; co-culture model; stiffness; synthetic peptide hydrogels
Publisher URL http://onlinelibrary.wiley.com/doi/10.1002/adfm.201702424/full
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
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.

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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