Layered skin-like hydrogel for long-acting drug release to achieve staged chronic wound healing

Chronic wounds severely threaten patient health and exacerbate the medical burden, with prolonged healing requiring long-term drug intervention. Current dressings cannot maintain effective therapeutic concentrations, and the complex healing process urgently needs long-acting treatment strategies. This study innovatively develops a biomimetic skin bilayer hydrogel: the upper layer, a GelMA-carboxylated cellulose nanocrystal (CNC) composite crosslinked by light, mimics the epidermal barrier to prevent secondary injury; the lower layer, based on GelMA and loaded with heparan sulfate (HS) in porous poly(dopamine) nanoparticles (PDA@NPs), simulates the angiogenic properties of the dermis. The porous structure of PDA@NPs enables higher HS loading, reinforces and integrates the interface, and, through spontaneous drug diffusion, forms a bottom-up concentration gradient drug delivery system for sustained release. This system accelerates wound repair through synergistic anti-inflammatory, vascular reconstruction, and physical barrier mechanisms, providing a safe and efficient new strategy for chronic wound management.