A multifunctional sandwich type wound dressing was designed in which two types of microspheres, one to alleviate the pain (ibuprofen) and the other to protect the wound from infections (Gentamicin or Ciprofloxacin), were embedded into bilayer chitosan sponge. pH of the wound increases from acidic (pH similar to 5) to basic (pH similar to 8) via infection, so pH-dependent antibiotic release system was designed using gelatin B microspheres to respond to increasing pH. Ibuprofen release from chitosan microspheres, on the other hand, was pH-independent not to intervene with pain management in changing pH conditions. Crosslinking with glutaraldehyde (GA) affected both release profile and size distribution of microspheres and 2.5% GA was chosen to obtain pH-responsive gelatin microspheres with narrow size distribution (80% of microspheres in between 15 and 25 mu m). The final system was found to be effective against both Staphylococcus aureus and Escherichia coli and changing pH seemed to affect the antimicrobial agent delivery as desired. (c) 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48252.