Tailoring composite hydrogel performance via controlled integration of norbornene-functionalised Pluronic micelles

Incorporating micelles into polymeric hydrogels offers a powerful route to combine the tuneable mechanical and structural properties of hydrogels with the precise drug-loading and release capabilities of nanocarriers. However, the method of micelle incorporation and its influence on hydrogel performance have yet to be studied in detail. Here, we present a modular strategy to tailor gelatin-norbornene hydrogels by integrating Pluronic® F127 micelles either physically or via covalent incorporation using norbornene-functionalised Pluronic (Pl_Nb). Pl_Nb was synthesised via Steglich esterification with >95% terminal functionalisation, forming stable, thermo-responsive micelles (2.5-15% w/v) with doxorubicin encapsulation efficiency of ∼80%, comparable to unmodified Pluronic. Micelles were either physically entrapped or chemically integrated into gelatin-norbornene networks via bioorthogonal thiol-ene crosslinking. The incorporation route dictated network mechanics and dynamics: chemical crosslinking conferred temperature-dependent behaviour and enhanced stress relaxation compared to physical crosslinking, whereas both incorporation routes reduced stiffness relative to neat hydrogels and slowed drug release compared to direct loading. All hydrogels were cytocompatible, and the released doxorubicin retained its bioactivity, reducing cancer cell viability. These findings establish micelle-hydrogel coupling as a versatile design approach for engineering biomaterials with potential in controlled therapeutic delivery and regenerative medicine.