Sticky Polyelectrolyte Shield for Enhancing Biological Half-Life of Growth Factors

Delivery of secretomes, which includes growth factors, cytokines, and mRNA, is critical in regenerative medicine for cell-to-cell communication. However, the harsh in vivo environment presents significant challenges for secretome delivery. Proteolytic enzymes shorten secretomes' half-lives, and secretomes tend to rapidly diffuse at defect sites. Therefore, a delivery system that ensures prolonged retention and enhanced therapeutic efficacy of secretomes is required. In this study, a Coating Optimized Drug Delivery Enhancement (COD₂E) system, a coacervate composed of dopamine functionalized fucoidan and poly-l-lysine, was fabricated for secretome delivery. The dopamine modification significantly enhanced adhesive strength (>7-fold) compared to that of the neat coacervates, which enabled rapid (5 min) and uniform coating ability on collagen sponges. The COD₂E system was able to encapsulate fibroblast growth factor (FGF2) and prolong the half-life of FGF2. Notably, its efficacy, demonstrated through a single application of FGF2 encapsulated COD₂E on collagen sponge, in a wound model demonstrated a successful tissue repair. The COD₂E system is an effective growth factor delivery vehicle since it can protect growth factors, has an antioxidant ability, adheres on various material surfaces, and is hemocompatible.