Evolving strategies for preventing biofilm on implantable materials SHAH RS, TATARA AM, D’SOUZA RN, MIKOS AG, & KASPER FK

Background Many implants are exposed to site bacteria Biofilm allows bacteria to increase antibiotic resistance and escape immune responses Biofilm contains mostly polysaccharide chains and extracellular DNA The polysaccharide network prevents the effects of antibiotics on the bacteria The persister theory offers a mechanism that explains why biofilm infections recur Biofilm producing bacteria stained with crystal violet

Past Attempts: working with materials For dental implants, surface roughness, implant morphology, and material used has been found to have little impact on biofilm formation Material choice is significant for orthopedic implants, PMMA as the most sensitive to bacterial colonization and titanium as the least ◦Antibiotic-loaded PMMA beads coating the implant surface harbor bacteria Vancomycin HCLTobramycin sulfate Culture media surrounding these constructs is rendered sterile by eluted antibiotics (circled areas indicate where culture media was spot-plated on an agar plate)

Present Attempts: local delivery of antibiotics Collagen sponges have good flexibility, coverage, and biocompatibility ◦releases most of the antibiotics too quickly Calcium sulfate is resorbable and has osteoconductive properties ◦autologous bone grafts are convenient Degradable polymer matrices, namely PLA and PLGA: ◦provide controlled release ◦preserve the drug’s bioactivity ◦release almost all of the drug

Future Approaches: Prevention D-amino acids are good dispersal agents due to low-cost and high potency Bacteriophages can lyse bacteria and disrupt the biofilm Some surface coatings resist biofilm and have anti-adhesive properties Coating the implants with bacteria that lack the virulence for an infection prevents adhesion of biofilm

Conclusions and Significance As knowledge of biofilms has grown, new methods of dealing with implant- associated infections have evolved Presently, as we treat biofilms with antibiotics, resistance is increasing Approaches that are necessary for current antibiotics to stay effective, such as ◦Competition using non-virulent species ◦Using agents that bacteria already synthesize ◦Synthetic materials ◦Bacteriophages