Thixotropic Peptide-Based Physical Hydrogels Applied to Three-Dimensional Cell Culture

Abstract

Pseudopeptides containing the d-Oxd or the d-pGlu [Oxd = (4R,5S)-4-methyl-5-carboxyl-oxazolidin-2-one, pGlu = pyroglutamic acid] moiety and selected amino acids were used as low-molecular-weight gelators to prepare strong and thixotropic hydrogels at physiological pH. The addition of calcium chloride to the gelator solutions induces the formation of insoluble salts that get organized in fibers at a pH close to the physiological one. Physical characterization of hydrogels was carried out by morphologic evaluation and rheological measurements and demonstrated that the analyzed hydrogels are thixotropic, as they have the capability to recover their gel-like behavior. As these hydrogels are easily injectable and may be used for regenerative medicine, they were biologically assessed by cell seeding and viability tests. Human gingival fibroblasts were embedded in 2% hydrogels; all of the hydrogels allow the growth of encapsulated cells with a very good viability. The gelator toxicity may be correlated with their tendency to self-assemble and is totally absent when the hydrogel is formed.

Synthesis and structure analysis of ferrocene‐containing pseudopeptides

“…The results herein reported show that in the ferrocene group forbids the formation of a defined secondary structure, even in the presence of the d ‐Oxd moiety that induces the formation of folded structures . A similar result has been observed by Wang, who reports that Fc–FF changed the conformation of the secondary structures from the flat β‐sheets conformation of phenylalanine–phenylalanine (FF) into twisted β‐sheets …”

A Multi‐Component Reaction towards the Development of Highly Modular Hydrogelators

“…This spontaneous self‐assembly process has emerged as an important way to develop functionalized materials, as demonstrated by the broad range of LMWGs that have been reported over the past several decades . The field of LMWGs is currently expanding due to their potential use in numerous applications such as drug delivery, tissue engineering and as scaffolds for 3D cell cultures …”

“…[1] The field of LMWGs is currently expanding due to their potentialu se in numerous applications such as drug delivery, [2] tissue engineering [3][4][5] and as scaffolds for 3D cell cultures. [6,7] Despitet he large number of LMWGs reportedi nt he literature, their gelation abilities/properties are still difficult to predict [1] and the linear synthesis of most gelator scaffolds severely restricts the fine-tuning of the gelatorf unctions, making their synthesisc ostly and time consuming. In this respect, multicomponent reactions where individualc omponents can be varied offers the possibility to access ad iversearray of gelators for the systematic discoveryo fn ew gel functionsa nd applications.…”

Peptide-Based Physical Gels Endowed with Thixotropic Behaviour

“…Pseudopeptides containing the D-Oxd or the D-pGlu [Oxd = (4 R ,5 S )-4-methyl-5-carboxyl-oxazolidin-2-one, p Glu = pyroglutamic acid] moiety and selected amino acids were used as low molecular weight gelators (LMWGs) to prepare strong and thixotropic hydrogels at a physiological pH (Figure 12). The addition of calcium chloride to the gelator solutions induces the formation of insoluble salts that are organized in fibers at a pH close to the physiological one [59]. As these hydrogels are easily injectable and may be used for regenerative medicine, they were biologically assessed by cell seeding and viability tests.…”

“…Data were expressed as relative percentage ± SD compared to control HGFs. Image adapted with permission from reference [59]. Copyright 2016 American Chemical Society.…”