Collagen is very important part of the fibrous proteins in the living organism. Animal tissues, especially tendons main structure contain collagen. In this investigation, natural collagen (coll) modified with differ- ent synthetic monomers such as 2-hydroxy ethylmethacrylate (HEMA) and acrylamide (AAm) was prepared as p(Coll-co-HEMA) and p(Coll-co-AAm) composites to enhance collagen natural characteristics. Biocompatibility of the prepared interpenetrating polymeric network (IPN) was tested with MTT Assay and found biocompat- ible. Model drugs, such as Trimetoprim (TMP) and Naproxene (NP) were used as antibacterial active agents for release studies from the synthesized composite hydrogel-collagen IPN matrices. The drug-loaded IPN films release studies were carried out in bio-mimetic media. It was found that collagen-synthetic polymer matrices can be readily prepared and used for drug delivery system in the release of active agents, providing great po- tential in wound dressing applications.