Enzymatically cross-linked hydrogels based on a linear poly(ethylene glycol) analogue for controlled protein release and 3D cell culture

Injectable and enzyme-mediated cross-linked hydrogels are promising biomedical materials. However, although poly(ethylene glycol) (PEG) is a popular basic component of synthetic hydrogels, only a few PEG-based enzymatically cross-linked hydrogels have been developed based on branched PEG. Compared with branched PEG, linear PEGs with different molecular weights are readily available and low-cost, while the poor capacity for post-polymerization modifications of linear PEG limited its application on a greater scale. Herein, a linear PEG-based analogue functionalized with multiple phenolic hydroxyl moieties, PEGDA-DTT-HPA, was designed and synthesized via Michael-type polyaddition combined with Steglich esterification. Environmentally friendly hydrogels composed of PEGDA-DTT-HPA were facilely formed under the catalysis of horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H2O2). The gelation time and mechanical strengths of hydrogels were found to be adjusted independently by altering the concentrations of HRP and H2O2, respectively. The hydrogels were further demonstrated as protein drug and cell carriers using bovine serum albumin (BSA) and lentivirus-mediated LifeAct-EGFP overexpressed human mesenchymal stem cells (hMSCs-LifeAct-EGFP), respectively. The BSA-loaded hydrogel systems exhibited a sustained drug release over 3 weeks; the encapsulated hMSCs showed good viability over all time points assessed. Consequently, the current study opens new avenues for the design of PEG-based injectable hydrogels and the PEGDA-DTT-HPA hydrogel has great potential for applications in drug delivery, 3D cell culture and tissue regeneration. © The Royal Society of Chemistry.