Desmosine-Inspired Cross-Linkers for Hyaluronan Hydrogels

Abstract

We designed bioinspired cross-linkers based on desmosine, the cross-linker in natural elastin, to prepare hydrogels with thiolated hyaluronic acid. These short, rigid cross-linkers are based on pyridinium salts (as in desmosine) and can connect two polymer backbones. Generally, the obtained semi-synthetic hydrogels are form-stable, can withstand repeated stress, have a large linear-elastic range, and show strain stiffening behavior typical for biopolymer networks. In addition, it is possible to introduce a positive charge to the core of the cross-linker without affecting the gelation efficiency, or consequently the network connectivity. However, the mechanical properties strongly depend on the charge of the cross-linker. The properties of the presented hydrogels can thus be tuned in a range important for engineering of soft tissues by controlling the cross-linking density and the charge of the cross-linker.

Organic liquid-crystal devices based on ionic conductors

“…31,[33][34][35][36][37] The properties of hydrogels can be tuned by adjusting the cross-linkers. [38][39][40] Hydrogels as tough as natural rubber have been demonstrated. 41,42 Hydrogels can retain water in low-humidity environment if they contain humectants, 32 or are encapsulated in low-permeability elastomers.…”

Charge Matters: Modulating Secondary Interactions in Hyaluronan Hydrogels

“…Taking inspiration from nature, we previously designed biocompatible crosslinkers based on elastin networks, with a pyridinium core and two spacers bearing reactive acrylamide end groups . The positive charge, characteristic for elastin's crosslinks, can easily be realized by N ‐alkylation of the pyridinium core in our system.…”

“…This provided us with two structurally similar crosslinkers containing a neutral ( 1 a ) and a positively charged ( 1 b ) aromatic core (Figure ). Formstable hydrogels were obtained based on these crosslinkers and high molecular weight, polydisperse hyaluronan in which 49% of carboxyl‐ groups had been thiolated . In the presented work, we focus on a detailed analysis of the secondary interactions occurring in these controlled network structures.…”

“…A range of HA‐hydrogels with varying degrees of thiolation and an average molecular weight of 74 kDa are designed in order to investigate charge dependent properties (Table S2 in SI). We kept the ratio of crosslinker to thiol constant at 0.8, but varied the degree of thiolation of HA polymers. Replacing carboxylic groups with thiolated linkers at different percentages gradually reduces the negative charge of the polymer.…”

Triazole-based cross-linkers in radical polymerization processes: tuning mechanical properties of poly(acrylamide) and poly(N,N-dimethylacrylamide) hydrogels

“…7 When transferring the design principles of biological hydrogels to synthetic hydrogels, the challenge is to identify structure-property relationships in order to obtain analogous rheological properties by a different molecular scaffold and cross-linking chemistry. To meet this challenge, we have previously developed desmosine-inspired cross-linkers based on 2,5-diacylpyridinium salts with terminal acrylamide units, which were used to cross-link partially thiolated hyaluronan via thiol-Michael reaction 8,9 and piperazinyl-functionalized poly(ethylene glycol) via aza-Michael reaction. 9,10 In a previous effort to simplify and streamline the synthetic access, we designed cross-linkers C n Mal and Me-C n + I À Mal with a neutral triazole or positively charged triazolium core and two terminal maleimides connected via alkyl spacers of various lengths (Fig.…”