StarPEG-Heparin Hydrogels to Protect and Sustainably Deliver IL-4

A major limitation for the therapeutic applications of cytokines is their short half‐life time. Glycosaminoglycans (GAGs), known to complex and stabilize cytokines in vivo, are therefore used to form 3D‐biohybrid polymer networks capable of aiding the effective administration of Interleukin‐4, a key regulator of the inflammatory response. Mimicking the in vivo situation of a protease‐rich inflammatory milieu, star‐shaped poly(ethylene glycol) (starPEG)‐heparin hydrogels and starPEG reference hydrogels without heparin are loaded with Interleukin‐4 and subsequently exposed to trypsin as a model protease. Heparin‐containing hydrogels retain significantly higher amounts of the Interleukin‐4 protein thus exhibiting a significantly higher specific activity than the heparin‐free controls. StarPEG‐heparin hydrogels are furthermore shown to enable a sustained delivery of the cytokine for time periods of more than two weeks. Primary murine macrophages adopt a wound healing supporting (M2) phenotype when conditioned with Interleukin‐4 releasing starPEG‐heparin hydrogels. The reported results suggest that GAG‐based hydrogels offer valuable options for the effective administration of cytokines in protease‐rich proinflammatory milieus such as chronic wounds of diabetic patients. Glycosaminoglycans are used to form 3D‐biohybrid polymer networks capable of aiding the effective administration of ZInterleukin‐4, a key regulator of the inflammatory response. The starPEG‐heparin hydrogels retain and sustainably deliver Interleukin‐4 for periods of more than two weeks. Primary murine macrophages adopt a wound healing phenotype (M2) when conditioned with Interleukin‐4 releasing starPEG‐heparin hydrogels.