Peptide hydrogels as novel scaffolds for dental pulp cell culture

Abstract

Functional scaffolds used for tissue regeneration should mimic the native extracellular matrix of tissues and allow recruitment and retention of stem cells whilst also promoting tissue organization and function. To achieve this, biomaterials used for scaffold fabrication should be biocompatible and allow attachment of cells which could be enhanced by the presentation of cell adhesion motifs, such as Arginine-Glycine-Aspartate (RGD). The use of hydrogel scaffolds is gaining popularity in regenerative endodontics whereby they can be used in combination with stem cells, derived from the dental pulp (DPCs), and/or growth factors for regeneration of the dentine-pulp complex.

In this project, the viability of DPCs was determined in vitro with inhouse synthesised ultrashort peptide hydrogels (NapFFKK-OH and NapFFK’K’-OH) as well as commercially available Biogelx hydrogels containing different percentages of RGD. Results showed that 0.5% w/v NapFFK’K’-OH hydrogel and 10% RGD Bioglex hydrogel were most promising for 3D culture of DPCs.

The DPC secretome in 3D hydrogel culture was investigated to assess the suitability of the hydrogels for engineering the dentine-pulp complex. Results showed that 0.5% w/v NapFFK’K’-OH hydrogel favoured the production of angiogenic and neurotrophic factors, such as regulated upon activation normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF), relative to culture in 10% RGD Biogelx hydrogel however, neither type of hydrogel was found to be favourable for osteogenic differentiation.

The emergence of antibiotic resistance and the inability of current endodontic treatments to completely eliminate the underlying infection in the dental pulp contribute to failure of endodontic therapies. To date very few hydrogels have been specifically designed to exhibit inherent antimicrobial properties. In this study it was shown that both NapFFK’K’-OH and 10% RGD Biogelx peptides displayed antimicrobial activities against the endodontic pathogens Staphylococcus aureus, Enterococcus faecalis and Fusobacterium nucleatum.

In conclusion, peptide hydrogels may have potential for future use in regenerative endodontic therapies based on their biocompatibility, with human dental pulp cells, their ability to secrete angiogenic and neurotrophic factors in 3D culture and their antimicrobial activity against endodontic pathogens.

Date of Award	Jul 2020
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Northern Ireland Department for the Economy & A. G. Leventis Foundation
Supervisor	Fionnuala Lundy (Supervisor), Garry Laverty (Supervisor) & Ikhlas El Karim (Supervisor)