Nontoxic Initiator Alternatives to TEMED for Redox Hydrogel Polymerization

Polymeric hydrogels are versatile biomaterials, offering unique advantages in tunability and biocompatibility that make them well-suited to a range of applications. Cross-linking, a fundamental step in hydrogel fabrication, is often initiated using a toxic redox system, ammonium persulfate (APS), and tetramethylethylenediamine (TEMED), which hinders hydrogel utility in direct contact with cells (e.g., wound dressings). To overcome this limitation, we developed alternative redox gelation systems that serve as nontoxic replacements for TEMED. The alternate initiators were either synthetic or bioinspired amine-containing polymers, Glycofect and polyethylenimine (PEI). Used with APS, these initiator candidates produced hydrogels with short gelation time and comparable moduli to TEMED-based gels and underwent further mechanical testing and biocompatibility characterization. While achieving mechanical properties similar to those of the control, the gels based on Glycofect and PEI outperformed TEMED-based gels in two cell viability studies, with Glycofect-initiated gels displaying significantly higher cytocompatibility. Taken together, these results indicate that Glycofect may serve as a drop-in replacement for TEMED to fabricate hydrogels with improved biocompatibility.