In Vitro Cytotoxicity of Redox Radical Initiators for Cross-Linking of Oligo(poly(ethylene glycol) fumarate) Macromers

Abstract

A novel hydrogel system based on oligo(poly(ethylene glycol) fumarate) (OPF) is currently being investigated as an injectable carrier for marrow stromal cells (MSCs) for orthopedic tissue engineering applications. This hydrogel is cross-linked using the redox radical initiators ammonium persulfate (APS) and ascorbic acid (AA). In this study, two different persulfate oxidizing agents (APS and sodium persulfate (NaPS)) with three reducing agents derived from ascorbic acid (AA, sodium ascorbate (Asc), and magnesium ascorbate-2-phosphate (Asc-2)) and their combinations were examined to determine the relationship between pH, exposure time, and cytotoxicity for rat MSCs. In addition, gelation times for specific combinations were determined using rheometry. pH and cell viability data after 2 h for combinations ranging from 10 to 500 mM in each reagent showed that there was a smaller pH change and a corresponding higher viability at lower concentrations, regardless of the reagents used. At 10 mM, there was less than a 1.5 unit drop in pH and greater than 90% viability for all initiator combinations examined. However, MSC viability was significantly reduced with concentrations of 100 mM and higher of the initiator combinations. At 100 mM, exposure to NaPS/Asc-2 resulted in significantly more live cells than exposure to APS/AA or NaPS/Asc, but at this concentration, NaPS/Asc-2 exhibited significantly longer OPF gelation onset times than APS/AA. At all combination concentrations, exposure time (10 min vs 2 h) did not significantly affect MSC viability. These data indicate that final pH and/or radical formation have a large impact on MSC viability and that multiple, intertwined testing procedures are required for identification of appropriate initiators for cell encapsulation applications.

Superparamagnetic iron oxide nanoparticles (SPIONs): Development, surface modification and applications in chemotherapy

“…Unsaturated polyesters are suitable candidates to stabilize such a system by forming a cross-linked network via their unsaturated double bonds, [23][24][25][26] which can be crosslinked by photocuring or chemical methods. Fumaric acid containing macromers are highly unsaturated and can be crosslinked with or without using a cross-linking agent to form their corresponding polymeric networks.…”

“…To our knowledge, this polymer has not been used as a SPION coating yet. 25 (Scheme 1). Specifically, 0.03 mol of PEG diol was dissolved in 100 mL of anhydrous methylene chloride (DCM) in a three-necked 250 mL reaction flask equipped with a reflux condenser and a magnetic stirrer.…”

Subcutaneous tissue response and osteogenic performance of calcium phosphate nanoparticle-enriched hydrogels in the tibial medullary cavity of guinea pigs

“…OPF gelation, i.e. the transition from flowable polymer precursor solution to hydrogel, occurs upon chemical crosslinking of macromers in a 10-15 minute time period and at 37°C [12,13]. These properties will potentially allow clinicians to prepare the material directly in the operating theatre, inject it into the desired site through a small incision, and close the wound after in situ gelation.…”

Two‐Step Protein Self‐Assembly in the Extracellular Matrix

“…However, hydrogel-based approaches inherently involve relatively large amounts of carrier material compared to the entrapped protein therapeutic. Toxicity concerns may arise from synthetic crosslinkers or initiators used in polymerization, [5] or modification of biological polymers. [6] Biocompatibility issues, such as the foreign body response, may be present at the interface between tissue and materials.…”