Multicomponent Peptide Hydrogels as an Innovative Platform for Cell-Based Tissue Engineering in the Dental Pulp

Abstract

In light of the increasing levels of antibiotic resistance, nanomaterials and novel biologics are urgently required to manage bacterial infections. To date, commercially available self-assembling peptide hydrogels have not been studied extensively for their ability to inhibit micro-organisms relevant to tissue engineering sites such as dental root canals. In this work, we assess the biocompatibility of dental pulp stem/stromal cells with commercially available multicomponent peptide hydrogels. We also determine the effects of dental pulp stem/stromal cell (DPSC) culture in hydrogels on growth factor/cytokine expression. Furthermore, to investigate novel aspects of self-assembling peptide hydrogels, we determine their antimicrobial activity against the oral pathogens Staphylococcus aureus, Enterococcus faecalis, and Fusobacterium nucleatum. We show that self-assembling peptide hydrogels and hydrogels functionalized with the adhesion motif Arg-Gly-Asp (RGD) are biocompatible with DPSCs, and that cells grown in 3D hydrogel cultures produce a discrete secretome compared with 2D-cultured cells. Furthermore, we show that soluble peptides and assembled hydrogels have antimicrobial effects against oral pathogens. Given their antibacterial activity against oral pathogens, biocompatibility with dental pulp stem/stromal cells and enhancement of an angiogenic secretome, multicomponent peptide hydrogels hold promise for translational use.

Antimicrobial and Anti-Inflammatory Activities of MAF-1-Derived Antimicrobial Peptide Mt6 and Its D-Enantiomer D-Mt6 against Acinetobacter baumannii by Targeting Cell Membranes and Lipopolysaccharide Interaction

“…These substitutions increased the net charge of Mt6 from +2 (MAF-1A) to +9. Gln ( 16 , 17 ) amino acids were replaced by Leu to increase the hydrophobicity. Lys ( 9 , 15 ) amino acids were replaced by Trp with large indole side chains to enhance the ability of the derived peptide to penetrate the cell membrane.…”

“…Due to their strong antibacterial action, antimicrobial peptides (AMPs) have emerged as new, promising drugs for the topical and systemic therapy of infectious diseases ( 15 , 16 ). In addition, Several AMPs have been proven to protect against biofilm development during bacterial colonization ( 17 – 19 ). Moreover, some cationic peptides exert immunomodulatory effects by neutralizing the ability of LPS to produce inflammatory cytokines ( 20 – 23 ).…”

Creating a Microenvironment to Give Wings to Dental Pulp Regeneration—Bioactive Scaffolds

“…As illustrated by relevant studies, the 3D culture of DPSCs can ameliorate the multidirectional differentiation potential and improve the mineralization level, helping to maintain the in vivo microenvironment of stem cells [ 111 , 112 ]. On that account, we primarily introduce three novel strategies to realize 3D culture.…”

“…Root canal environments expected to realize pulp regeneration in clinical practice may still have residual bacterial toxin components, which raises an antibacterial requirement for pro-regenerative scaffolds, including hydrogels, nanomaterials, microspheres, etc. For instance, Afami et al [ 112 ] developed functionalized hydrogels with cell adhesion motifs for the 3D culture of DPSCs, which had antibacterial activity against common bacteria in the root canal. As was precisely described in relevant studies [ 195 , 196 ], a low concentration of graphene oxide-copper composites can give an impetus to odontogenic differentiation of DPSCs while inhibiting the formation of biofilm from Streptococcus mutans.…”

Highly Synergistic Properties of Multicomponent Hydrogels Thanks to Cooperative Nucleopeptide Assemblies

“…Moreover, the multicomponent approach has been reported to bring new properties such as photophysical 30,31 or electronic 32 ones, biofunctionalization, 33−35 or also further sensitivities to stimuli such as temperature, 29 pH, 36−38 or several of them 39 (i.e., multi-responsivity). However, applications of multicomponent peptide-based hydrogels are still in their infancy, mainly harnessed in a biological context (e.g., for wound dressing 40 and dental care 41 ) thanks to their good biocompatibility. 23,26,42−44 The formulation of such soft materials remains challenging because depending on the structure of the peptides, their possible chemical modification(s), and the experimental conditions/mode of preparation, three main types of assemblies can occur, 10,11 known as (i) self-sorting (i.e., in which each gelator self-assembles with the same gelator); 36,38,45 (ii) co-assembling (i.e., several gelators interact each other) which can be cooperative (i.e., exhibiting a certain degree of organization) or random; 24,26,40,46 and (iii) disruptive.…”