Stem cell-derived secretomes have emerged as promising cell-free therapeutics for wound healing. However, their rapid clearance from the wound site limits therapeutic efficacy, highlighting the need for biomaterial platforms capable of temporally controlled release. Degradable hydrogels provide an attractive solution for sustained therapeutic delivery, yet the nanoscale structural changes governing hydrogel degradation and cargo release remain poorly understood. Understanding these structure-property relationships is essential for the rational design of advanced biomaterial delivery systems.
In this study, we developed photo-curable Pluronic-based hydrogels with tunable degradation profiles for controlled secretome delivery. Pluronic F127 was functionalised with hydrolysable oligolactide or oligoglycolide linkers followed by methacrylation to produce thermoresponsive hydrogels with distinct degradation behaviours. Hydrogel degradation and release kinetics were evaluated using FITC-labelled bovine serum albumin (BSA) and fluorescent particles (0.03 µm and 0.1 µm) as model secretome components, while the biological activity of released secretome was assessed using an in vitro scratch wound assay. We found that, lactide-modified hydrogels degraded over approximately one month, whereas glycolide-modified hydrogels degraded within a few days. By varying the ratio of the degradable polymers together with photoinitiator and chain transfer agent concentration, hydrogel degradation and release kinetics could be precisely controlled. Release profiles exhibited pronounced size dependence, with smaller soluble molecules released earlier than larger vesicle-like components. Controlled secretome release significantly enhanced cell migration and wound closure compared with untreated controls.
Building on these findings, BioSAXS measurements at the Australian Synchrotron scheduled for September 2026 will investigate how nanoscale hydrogel architecture depends on synthesis condition, how it evolves during degradation, and how these structural changes correlate with degradation behaviour and release kinetics. The resulting structure-property relationships will guide the rational design of degradable biomaterial platforms for temporally controlled secretome delivery and regenerative wound healing applications.