Summary

Patients with diabetic osteomyelitis suffer from infectious ulceration. More than 85% cases report ulcer formation before the condition of amputation is reached. Antibioic infusion remains an essential therapy but cannot be done in a sustained manner. Sustained release polymeric or ceramic cements available often aggravate the situation by acting as a nidus to the pathogens. One of the reason is antibiotics fade in their activity if left, in physiological condition for longer time. Antimicrobial polymers can be employed in such cases for their antimicrobial properties. These polymers are large does not decay fast and can kill the microbes by just being in contact due to their poly-cationic effect. Hence even if the antibiotics fade, the polymer will hold the rein. Carboxymethyl-chitosan (CMC) is one of such anti-microbial polymer. In the current work we propose to use CMC crosslinked with genipin impregnated with a specific antibiotic fortified with densifying ionic polymer can really manage diabetic osteomyelitis in situ. Another important thing, the polymeric gels or beads are transparent to X-ray hence it is difficult to trace it non-invasively. In this case elemental barium will be added to the polymeric bulk so as to make it X-ray-translucent. Elemental barium is non-toxic to much extent in human body. One of the densifying ionic polymers may be polyamidomine (PAMAM) dendrimers which is already known for its antimicrobial properties. The polymer mix, gel/ beads and eluted drug will be evaluated using spectroscopic methods and anti-microbial culture methods. The system will be initially evaluated through in vitro cell culture studies followed by test in in vivo murine model.

Major Objectives

• Preparation of CMC based highly effective antimicrobial and poly-ionic polymer mix and in vitro anti-microbial study.
• Preparation of gels/ beads out of the mix by genipin crosslinking and characterization.
• Impregnation of antiobiotic in the gel/ bead system and study of release kinetics.
• Impreganation of Barium to make the gel x-ray translucent/opaque and characterization.
• In vitro cytocompatability testing and testing the gel/ beads in vivo in diabetic osteomyelitis murine model.