In this work, hybrid hydrogels composed of bacterial cellulose nanofibers (nf-BC) and sodium alginate (SA) were prepared as a dual-stimuli responsive release system. The pH and electric field stimulus-responsive swelling properties and the stimulus-responsive drug release behaviors of the nf-BC/SA hybrid hydrogels using Ibuprofen as a model drug, were investigated in vitro. As the pH changed from 1.5 to 11.8, the swelling ratio increased from less than 8 times compared with its dry weight at acidic conditions to more than 13 times when the pH value was 11.8. When the electric field changed from 0 to 0.5 V, the hybrid hydrogels also showed an increasing swelling ratio from 8 times to 14 times their dry weight. The release of Ibuprofen (IBU) could be controlled by the action of deprotonation or protonation of calcium alginate in the hydrogels under different pH conditions, faster in alkaline conditions and slower in acidic conditions. Furthermore, the drug release from the hybrid hydrogels could be enhanced with an applied electric stimulus. The drug release mechanism under pH and applied electric field could be interpreted by the superposition of both Fickian diffusion and case-II transport based on Peppas' semi-empirical equation. The nf-BC/SA hybrid hydrogels with dual pH- and electro-response were new promising candidates as controlled drug delivery systems.

Significance: Wound dressings are frequently used for wound covering and healing. Ideal wound dressings should provide a moist environment for wounds and actively promote wound healing and skin recovery. The materials used as ideal wound dressings should possess specific properties, thus accelerating skin tissue regeneration process. Recent Advances: Bacterial cellulose (BC) is a natural polymer synthesized by some bacteria. As a kind of natural biopolymer, BC shows good biological activity, biodegradability, and biological adaptability. It has many unique physical, chemical, and biological properties, such as ultrafine nanofiber network, high crystallinity, high water absorption and retention capacity, and high tensile strength and elastic modulus. These excellent properties of BC have laid the foundation for its application as dressing in wound healing. Critical Issues: To optimize the biocompatibility and antimicrobial activity of BC, different methods including microbial fermentation, physical modification, chemical modification, and compound modification have been adopted to modify BC to ensure a better application in wound healing. BC-based wound dressings have been applied in infected wounds, acute traumatic injuries, burns, and diabetic wounds, showing remarkable therapeutic effects on promoting wound healing. Furthermore, there have been some commercial BC-based dressings and they have been utilized in clinical practice. Future Directions: Because of its excellent physicochemical characteristics and biological properties, BC shows high clinical value to be used as a wound dressing for skin tissue regeneration.