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Evaluation of Tissue Interactions with Mechanical Elements of a Transscleral Drug Delivery Device
Charles Stark Draper Laboratory, 555 Technology Square, Cambridge, MA 02139, USA
Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA
* Author to whom correspondence should be addressed.
Received: 13 February 2012; in revised form: 29 February 2012 / Accepted: 29 February 2012 / Published: 12 March 2012
Abstract: The goal of this work was to evaluate tissue-device interactions due to implantation of a mechanically operated drug delivery system onto the posterior sclera. Two test devices were designed and fabricated to model elements of the drug delivery device—one containing a free-spinning ball bearing and the other encasing two articulating gears. Openings in the base of test devices modeled ports for drug passage from device to sclera. Porous poly(tetrafluoroethylene) (PTFE) membranes were attached to half of the gear devices to minimize tissue ingrowth through these ports. Test devices were sutured onto rabbit eyes for 10 weeks. Tissue-device interactions were evaluated histologically and mechanically after removal to determine effects on device function and changes in surrounding tissue. Test devices were generally well-tolerated during residence in the animal. All devices encouraged fibrous tissue formation between the sclera and the device, fibrous tissue encapsulation and invasion around the device, and inflammation of the conjunctiva. Gear devices encouraged significantly greater inflammation in all cases and a larger rate of tissue ingrowth. PTFE membranes prevented tissue invasion through the covered drug ports, though tissue migrated in through other smaller openings. The torque required to turn the mechanical elements increased over 1000 times for gear devices, but only on the order of 100 times for membrane-covered gear devices and less than 100 times for ball bearing devices. Maintaining a lower device profile, minimizing microscale motion on the eye surface and covering drug ports with a porous membrane may minimize inflammation, decreasing the risk of damage to surrounding tissues and minimizing disruption of device operation.
Keywords: age-related macular degeneration; drug delivery; transscleral
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Cite This Article
MDPI and ACS Style
Cohen, S.J.; Chan, R.V.P.; Keegan, M.; Andreoli, C.M.; Borenstein, J.T.; Miller, J.W.; Gragoudas, E.S. Evaluation of Tissue Interactions with Mechanical Elements of a Transscleral Drug Delivery Device. Pharmaceutics 2012, 4, 212-229.
Cohen SJ, Chan RVP, Keegan M, Andreoli CM, Borenstein JT, Miller JW, Gragoudas ES. Evaluation of Tissue Interactions with Mechanical Elements of a Transscleral Drug Delivery Device. Pharmaceutics. 2012; 4(1):212-229.
Cohen, Sarah J.; Chan, Robison V. Paul; Keegan, Mark; Andreoli, Christopher M.; Borenstein, Jeffrey T.; Miller, Joan W.; Gragoudas, Evangelos S. 2012. "Evaluation of Tissue Interactions with Mechanical Elements of a Transscleral Drug Delivery Device." Pharmaceutics 4, no. 1: 212-229.