Photocrosslinked Alginate-Methacrylate Hydrogels with Modulable Mechanical Properties: Effect of the Molecular Conformation and Electron Density of the Methacrylate Reactive Group

Abstract

Hydrogels for load-bearing biomedical applications, such as soft tissue replacement, are required to be tough and biocompatible. In this sense, alginate-methacrylate hydrogels (H-ALGMx) are well known to present modulable levels of elasticity depending on the methacrylation degree; however, little is known about the role of additional structural parameters. In this work, we present an experimental-computational approach aimed to evaluate the effect of the molecular conformation and electron density of distinct methacrylate groups on the mechanical properties of photocrosslinked H-ALGMx hydrogels. Three alginate-methacrylate precursor macromers (ALGMx) were synthesized: alginate-glycidyl methacrylate (ALGM1), alginate-2-aminoethyl methacrylate (ALGM2), and alginate-methacrylic anhydride (ALGM3). The macromers were studied by Fourier-transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H-NMR), and density functional theory method (DFT) calculations to assess their molecular/electronic configurations. In parallel, they were also employed to produce H-ALGMx hydrogels, which were characterized by compressive tests. The obtained results demonstrated that tougher hydrogels were produced from ALGMx macromers presenting the C=C reactive bond with an outward orientation relative to the polymer chain and showing free rotation, which favored in conjunction the covalent crosslinking. In addition, although playing a secondary role, it was also found that the presence of acid hydrogen atoms in the methacrylate unit enables the formation of supramolecular hydrogen bonds, thereby reinforcing the mechanical properties of the H-ALGMx hydrogels. By contrast, impaired mechanical properties resulted from macromer conditions in which the C=C bond adopted an inward orientation to the polymer chain accompanied by a torsional impediment.

A Biomimetic Platelet-Rich Plasma-Based Interpenetrating Network Printable Hydrogel for Bone Regeneration

“…Methacrylated alginate (M-ALG) was synthesized from the reaction between the hydroxyl group of alginate and the epoxy group of methacrylic anhydride under alkaline conditions, the mechanisms of which include epoxide ring-opening, carbodiimide chemistry and transesterification ( Araiza-Verduzco et al, 2020 ). The reaction is schematically shown in Figure 1A , and the structures of neat ALG and M-ALG were confirmed by 1 HNMR spectroscopy in D 2 O ( Figure 1B ), depicting characteristic peaks between 3.50 and 5.20 ppm from both neat ALG and M-ALG due to their saccharide units.…”

Alginate Modification and Lectin-Conjugation Approach to Synthesize the Mucoadhesive Matrix

“…Another representative strategy prompting the covalent crosslinking in alginate is free radical polymerization. Alginate-methacrylate hydrogels can be prepared through photopolymerization, obtaining mechanical properties that are dominated by the molecular conformation and electron density of the methacrylate reactive groups [35]. Nevertheless, if the alginate polymer chain's surface is decorated with cell adhesion ligands, cell cross linking most likely also produces alginate gels [36].…”

Self-Standing Photo-Crosslinked Hydrogel Construct: in vitro Microphysiological Vascular Model

“…Methacrylate modified alginate dissolved in deuterated water (D 2 O) was analyzed using nuclear magnetic resonance ( 1 H-NMR; Bruker JNM-a500 spectrometer) at 500 MHz. The characteristic peaks for acrylate modification were identified and the degrees of methacrylate substitution were determined by calculating the integrals of vinyl-specific peaks with respect to parent polysaccharide peaks as mentioned elsewhere [Araiza-Verduzco et al, 2020].…”