Reducing Infection and Plugging of Tympanostomy Tubes Through Zwitterionic Thin Films

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PROJECT SUMMARY Although tympanostomy tube (TT or ear tube) placement is a simple and common surgery (754,000/year in the US), complications arise in a subset of patients, particularly post-TT otorrhea (PTTO, 26%) due to bacterial biofilms and mucus plugging (7-34%). There is an urgent need to reduce these complications and enhance the functional longevity of TTs. Modification of TT surfaces to prevent bacterial adhesion and to reduce mucus adhesion could dramatically reduce these complications. We recently developed a novel photochemically driven process that simultaneously forms and grafts zwitterionic thin films onto polymeric materials used to fabricate TTs (e.g. PDMS). These thin films are polymerized from either sulfobetaine methacrylate (SBMA) or carboxybetaine methacrylate (CBMA) monomers. The CBMA/SBMA polymer chains are crosslinked to each other during polymerization by polyethylene glycol dimethacrylate (PEGDMA). We find that both CBMA and SBMA thin films prevent adhesion by an order of magnitude from fibrinogen, platelets, macrophages, fibroblasts, and importantly, Staphylococcus aureus and Staphylococcus epidermidis. We propose to extend these promising findings into TTs, while determining how changes in crosslinking density affect end properties. The overall objective of this research is to determine the ability of zwitterionic thin films grafted onto the surface of TTs to prevent the complex phenomena of bacterial colonization and mucus plugging. We hypothesize that CBMA and SBMA zwitterionic thin films will prevent bacterial adhesion and reduce mucus plugging on TTs. We will test this hypothesis by undertaking the following Specific Aims. 1) Determine the effect of CBMA and SBMA thin films on bacteria adhesion from Staphylococcus aureus and Pseudomonas aeruginosa on TTs. We will test this effect by quantifying bacterial adhesion on PDMS surfaces using validated in vitro models. We will also expose rats that have been implanted with zwitterionic coated or bare TTs with either S. aureus or P aeruginosa to induce biofilm formation. 2) Investigate the ability of CBMA and SBMA thin films to reduce mucus adhesion, mucus drying, and mucus plug formation on TT surfaces. To test this, we will first examine the adhesion and drying of porcine intestinal mucus on PDMS that have been coated with thin films or remain uncoated. Finally, we will test the mucus plugging on coated and uncoated TTs inserted into rat tympanic membranes. When successful, these aims will implicate a novel and highly effective method to prevent common complications of TTs by preventing biofilm and mucus plug formation. Beyond TTs, the results will be broadly applicable to devices which suffer from biofouling. This innovation will reduce the PTTO complications currently suffered by ~50,000 US children per year and thus support the Mission, Goals, and Objectives of the NIDCD.