title: Suppression of scarring in peripheral nerve implants by drug elution.
abstract: OBJECTIVE
  Medical implants made of non-biological materials provoke a chronic inflammatory response, resulting in the deposition of a collagenous scar tissue (ST) layer on their surface, that gradually thickens over time. This is a critical problem for neural interfaces. Scar build-up on electrodes results in a progressive decline in signal level because the scar tissue gradually separates axons away from the recording contacts. In regenerative sieves and microchannel electrodes, progressive scar deposition will constrict and may eventually choke off the sieve hole or channel lumen. Interface designs need to address this issue if they are to be fit for long term use. This study examines a novel method of inhibiting the formation and thickening of the fibrous scar.
  
  
  METHODS
  Research to date has mainly focused on methods of preventing stimulation of the foreign body response by implant surface modification. In this paper a pharmacological approach using drug elution to suppress chronic inflammation is introduced. Microchannel implants made of silicone doped with the steroid drug dexamethasone were implanted in the rat sciatic nerve for periods of up to a year. Tissue from within the microchannels was compared to that from control devices that did not release any drug.
  
  
  RESULTS
  In the drug eluting implants the scar layer was significantly thinner at all timepoints, and unlike the controls it did not continue to thicken after 6 months. Control implants supported axon regeneration well initially, but axon counts fell rapidly at later timepoints as scar thickened. Axon counts in drug eluting devices were initially much lower, but increased rather than declined and by one year were significantly higher than in controls.
  
  
  CONCLUSIONS
  Drug elution offers a potential long term solution to the problem of performance degradation due to scarring around neural implants.
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: James J
authors.initials: JJ
authors.lastname: FitzGerald
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D002921:Cicatrix / Q000188:drug therapy* / Q000209:etiology; D003907:Dexamethasone / Q000008:administration & dosage; D004343:Drug Implants / Q000008:administration & dosage*; D065546:Drug Liberation; D004567:Electrodes, Implanted / Q000009:adverse effects*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000187:drug effects* / Q000473:pathology
chemical_list: D004343:Drug Implants; D003907:Dexamethasone