Electrospun fibers of hydrophilic polymers meet challenges in a rapid degradation of fiber matrices and discharge of antibiotics to comply with requirements of infection control as a dermal regeneration template. In the current study, a pH conversion process is initially developed to ensure fluent electrospinning, an efficient in situ cross-linking of electrospun gelatin fibers with oxidized alginate and simultaneous loading of gentamicin sulfate (GS) and hydrophobic ciprofloxacin into fibers. The dual drug-loaded fibers indicate a complete release of GS during 6 d and a sustained release of ciprofloxacin for over three weeks, and the antibiotics release indicates significant growth inhibitions on Pseudomonas aeruginosa and Staphylococcus epidermidis. The wound healing efficacy is evaluated on a deep burn model infected with 10 8 CFU of P. aeruginosa. Compared with fibers with loaded individual drugs, the concomitant release of GS and ciprofloxacin significantly reduces the bacteria numbers in wound and livers, at around 2.30 x 10(5) and 1.25 x 10(3) CFU after 3 d, respectively. The wound re-epithelization, blood vessel formation, collagen deposition, and tissue remodeling process are accelerated with a complete healing observed after 21 d. This study provides a feasible strategy to design cross-linked hydrophilic fibers with an extended drug release for biomedical applications.