Research

Thermal Treatment of Medical Implant Infections
The Nuxoll Lab has introduced a new approach to tackling bacterial biofilm infections on medical implants:  We aim to thermally treat the biofilm in situ using a polymer / magnetic nanoparticle composite coating which converts magnetic field energy into localized heat.  Our long-term goal for this technology is to replace most explantation and reimplantation surgeries with a non-invasive outpatient procedure based on a carefully designed composite coating.

Thermal deactivation studies
Though thermal treatment of biofilms in autoclaves (121 °C) is well established, surprisingly little is known about the degree of cell-death at more physiologically accessible temperatures.  Our lab has quantified thermal mitigation of Pseudomonas aeruginosa biofilms by thermal shocks from 50 to 80 °C for exposure times from 1 to 30 minutes, demonstrating decreases in colony forming units (CFU) of up to six orders of magnitude and demonstrating that the degree of cell-death can be described by an Arrhenius-style temperature dependence with a Weibull-style dependence on exposure time, matching the experimental CFU counts to within half an order of magnitude across the entire parameter space (O’Toole, Biofouling).  These trials required drip-flow reactor biofilms with initial bacteria loads far higher (greater than 108 CFU cm-2) than are likely to occur clinically.  Starting with lower density (less than 106 CFU cm-2) shaker plate biofilms, 80 °C thermal shocks decrease the CFU count below quantification, though 50 °C thermal shock has no discernable effect across a variety of common bacterial and mammalian cell culture media (Ricker, in preparation).  In the course of these studies we have also created a MATLAB program to automatically apply an objective thresholding algorithm to confocal fluorescent microscopy image stacks for biofilm characterization (Ricker, in preparation) and are currently investigating the suitability of colorimetric MTT assays for biofilm quantification.
 
Biofilm thermal shock grid

Average log(CFU cm-2) for biofilm thermal shock experiments.  Heat shocks at 37°C were comparable controls. As heat shock temperature or exposure time increases, the average log(CFU cm-2) decreases. SDs (n ≥ 9) are indicated with ±. Bright red cells indicate large CFU densities while bright blue cells indicate low CFU densities. From Biofouling.


Biofilm colony counts vs. time and temperature

Average log(CFU cm-2) of thermally shocked DFR biofilms as a function of temperature and exposures time. Error bars indicate SDs of log(CFU cm−2) averages (n ≥ 9). Dashed line indicates a minimum quantification limit of 1.12.  From Biofouling.


                                (CFU/cm2 ) = (CFU/cm2 )0 *10-0.079(T-37) * t-0.044(T-37)
      Analytical function for biofilm bacterial density, where T is in °C and t is in minutes.

Thermal Modeling
We are also building computational and experimental models of physiological heat transfer from the coatings to estimate the degree of collateral tissue damage.  This work has already produced the first pourable, volume-stable hydrogel tissue phantom, which will conform to any geometry, gel in less than a minute, and maintain its swelling ratio for weeks with < 1% deviation. It maintains its volume and mechanical stability at elevated temperatures (80 °C) and its thermal conductivity can be tuned across a wide range using dispersed fillers with different thermal properties (Coffel, Int J Poly Mater). 



Coating development
The heating power (termed specific absorption rate (SAR)) requirements of these coatings require magnetite loadings more than an order of magnitude higher than previously investigated composites, exposing new complications in the coating design.  Surprisingly, under these conditions the orientation of the coating within the magnetic field has a larger effect on its heating ability (per iron mass) than the polymer type, solvent type, coating thickness, or magnetite concentration (Coffel, J Mater Chem B).

Magnetite composite SAR

Specific absorption rate of Poly(vinyl alcohol) and Poly(styrene) composites for all thicknesses and iron concentrations; all samples were tested in positions perpendicular and parallel to an applied alternating magnetic field  in water (A and B) and dodecane (C and D); n = 3 for all measurements.  From J. Mater. Chem. B .