Effects of free radical initiators on polyethylene glycol dimethacrylate hydrogel properties and biocompatibility

Abstract

Many studies have utilized Irgacure 2959 photopolymerized poly(ethylene glycol) (PEG) hydrogels for tissue engineering application development. Due to the limited penetration of ultraviolet light through tissue, Irgacure 2959 polymerized hydrogels are not suitable for use in tissues where material injection is desirable, such as the spinal cord. To address this, several free radical initiators (thermal initiator VA044, ammonium persulfate (APS)/TEMED reduction-oxidation reaction, and Fenton chemistry) are evaluated for their effects on the material and mechanical properties of PEG hydrogels compared with Irgacure 2959. To emulate the effects of endogenous thiols on in vivo polymerization, the effects of chain transfer agent (CTA) dithiothreitol on gelation rates, material properties, Young's and shear modulus, are examined. Mouse embryonic stem cells and human induced pluripotent stem cell derived neural stem cells were used to investigate the cytocompatibility of each polymerization. VA044 and Fenton chemistry polymerization of PEG hydrogels both had gelation rates and mechanical properties that were highly susceptible to changes in CTA concentration and showed poor cytocompatibility. APS/TEMED polymerized hydrogels maintained consistent gelation rates and mechanical properties at high CTA concentration and had a similar cytocompatibility as Irgacure 2959 when cells were encapsulated within the PEG hydrogels. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3059-3068, 2017.

Combination of IKVAV, LRE, and GPQGIWGQ Bioactive Signaling Peptides Increases Human Induced Pluripotent Stem Cell Derived Neural Stem Cells Extracellular Matrix Remodeling and Neurite Extension

“…Cellular viability and matrix properties are affected by radical initiator choice for gelation. [ 29 ] To select a radical initiator for these studies, the effects of ammonium persulfate (APS)/tetramethylethylenediamine (TEMED) and the more commonly used Irgacure 2959 photoionization method on hNSC viability were compared. Both radical initiators lead to similar cellular viability in the matrices (Figure S1, Supporting Information, Irgacure 2929/UVA: DIFF‐HA = 88.8% ± 6.2% & IKVAV and LRE peptides tethered to DIFF‐HA (PEP‐HA) = 87.5% ± 10.2%, APS/TEMED: DIFF‐HA = 83% ± 13.7% & PEP‐HA = 87.4% ± 10.2%).…”

“…hNSC derived from the ND2.0 human induced pluripotent stem cell line were isolated from neural rosettes after 10 d of neural differentiation from the pluripotent state according to a previously published protocols. [ 56 ] Similar to previous studies, [ 16,27,29,32,38 ] hNSC were then expanded on Matrigel coated flasks in N2B27 maintenance media (50% F12/DMEM, 50% Neurobasal medium, 1% Glutamax, 1% nonessential amino acids, 0.5% N2 supplement, 1% B27 supplement, 1% penicillin/streptomycin and 20 ng mL −1 FGF‐2). For cell encapsulation studies, 100 000 hNSC (passage 12) per mL of matrix was used.…”

Effect of Laminin Derived Peptides IKVAV and LRE Tethered to Hyaluronic Acid on hiPSC Derived Neural Stem Cell Morphology, Attachment and Neurite Extension

“…Human-Induced Pluripotent Stem Cell Derived Neural Stem Cell (hNSC) Culture: hNSC derived from the ND2.0 human induced pluripotent stem cell line were isolated from neural rosettes after 10 days of neural differentiation from the pluripotent state according to a previously published protocol [42,43]. Similar to previous studies [37,39,44,45], hNSC were then expanded on Matrigel coated flasks in N2B27 maintenance media (50% F12/DMEM, 50% Neurobasal medium, 1% Glutamax, 1% non-essential amino acids, 0.5% N2 supplement, 1% B27 supplement, 1% penicillin/streptomycin and 20 ng/mL FGF-2). For 2D studies, 25,000 hNSC (passage 12) were plated in each well of a 24-well plate unless otherwise noted.…”

Polyethylene glycol in spinal cord injury repair: a critical review

“…Wilems et al investigated the use of other free radical initiators such as ammonium persulfate (APS)/ tetramethylethylenediamine (TEMED), VA044 (a thermal initiator), and a Fenton chemistry reaction (driven by glucose/ glucose oxidase oxidation/reduction of Fe). 8 APS/TEMED was determined to be the most viable replacement for Irgacure 2959 of the tested initiators in that study.…”

“…End-group modification with different reactive moieties makes it possible for PEG to participate in covalent bonding through a number of chemistries ( Figure 1 ). 8 – 14 Attaching PEG through covalent or noncovalent interactions can prolong the circulation of proteins, peptides, and other molecules without compromising their bioactivity. 15 , 16 In addition to PEGylation (bioconjugation), PEG can be cross-linked to form porous hydrogels, which can serve as biocompatible matrices that can closely mimic the extracellular matrix (ECM) found in tissues.…”