An injectable sequential dual-crosslinking catechol-functionalized hyaluronic acid hydrogel for enhanced regeneration of full-thickness burn injury.

ABSTRACT

Severe burn injuries with massive dermal loss are often underestimated despite their significant impact on morbidity and mortality. Resembling the natural extracellular matrix (ECM), hyaluronic acid (HA)-based dressings have been extensively explored as suitable candidates for burn wound treatment. However, native HA hydrogel's limitations, such as low mechanical strength, rapid degradation, and uncontrollable drug delivery, hinder its efficacy, especially for full-thickness burns requiring injectable hydrogels with robust antibacterial and angiogenic capabilities. Herein, we present a novel multifunctional sequential dual-curing hydrogel system, combining hyperbranched poly(DMA-DMAPMA-PEGDA) (DDP) polymer with thiolated hyaluronic acid (HA-SH). The DDP copolymer, featuring multi-vinyls and catechol functionalities, facilitates two curing reactions taking place sequentially with HA-SH under physiological conditions, balancing convenient injection with the mechanical strength essential for effective wound management. Furthermore, the resulting DDP/HA hydrogels demonstrate enhanced therapeutic attributes, including intrinsic angiogenic and antimicrobial effects, setting them as promising dressing options for deep burn wound therapy.