Reduced foreign body response at nitric oxide-releasing subcutaneous implants.
The tissue response to nitric oxide (NO)-releasing subcutaneous implants is presented. Model implants were created by coating silicone elastomer with diazeniumdiolate-modified xerogel polymers capable of releasing NO. The host tissue response to such implants was evaluated at 1, 3, and 6 weeks and compared to that of uncoated silicone elastomer blanks and xerogel-coated controls incapable of releasing NO. Delivery of NO (approximately 1.35 micromol/cm2 of implant surface area) reduced foreign body collagen capsule ("scar tissue") thickness by >50% compared to uncoated silicone elastomer after 3 weeks. The chronic inflammatory response at the tissue/implant interface was also reduced by >30% at NO-releasing implants after 3 and 6 weeks. Additionally, CD-31 immunohistochemical staining revealed approximately 77% more blood vessels in proximity to NO-releasing implants after 1 week compared to controls. These findings suggest that conferring NO release to subcutaneous implants may promote effective device integration into healthy vascularized tissue, diminish foreign body capsule formation, and improve the performance of indwelling medical devices that require constant mass transport of analytes (e.g., implantable sensors).
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Evan M
EM
Hetrick
Heather L
HL
Prichard
Bruce
B
Klitzman
Mark H
MH
Schoenfisch
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry*; D004343:Drug Implants / Q000008:administration & dosage*; D005547:Foreign Bodies / Q000209:etiology* / Q000517:prevention & control*; D020007:Implants, Experimental / Q000009:adverse effects*; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004337:Drug Carriers; D004343:Drug Implants; D009569:Nitric Oxide