Reduced foreign body response at nitric oxide-releasing subcutaneous implants
Open accessAbstract
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).
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Hetrick et al. found that nitric oxide reduced collagen encapsulation by about 20-25% versus controls at 3 and 6 weeks, mitigated inflammation, and appeared to enhance vascular density at 1 and 3 weeks.
“In addition to reduced collagen encapsulation (~20–25% vs. controls) observed at 3 and 6 weeks, the NO mitigated inflammation (determined by reduced inflammatory cells near the implant) and appeared to enhance vascular density at 1 and 3 weeks.238”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [238]
The anti-inflammatory effect correlated with nitric oxide release duration, indicating that benefits may only persist while the interface is releasing nitric oxide, in contrast to Hetrick et al. where long-term reduction in inflammation was observed after cessation of release.
“The anti-inflammation correlated with the NO-release duration indicating that the observed benefits may only persist as long as the interface is releasing NO, in contrast to observations by Hetrick et al. where long-term reduction in inflammation were observed after cessation of NO release.103,238”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [238]
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References 46 · Cited by 158
Research works printed but not linked: 1
- [29]Pett MA. Nonparametric statistics for health care research. Thousand Oaks, CA: SAGE Publications; 1997. [Google Scholar]
- Authors
- Hetrick, E. M., Prichard, H. L., Klitzman, B., & Schoenfisch, M. H.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Duke University (US)
- Corresponding author
- Schoenfisch, Mark H.
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 28
- Issue
- 31
- Pages
- 4571-4580
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC2692676
- OpenAlex
- W2054343135
- Cited by
- 158
- References
- 46
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 8 · 2022: 5 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 9 · 2017: 10 · 2016: 16 · 2015: 10 · 2014: 7 · 2013: 17 · 2012: 9
- FWCI
- 6.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Eastman Chemical Company
- National Institutes of Health
- National Institute of Biomedical Imaging and Bioengineering (EB 000708, R01EB000708)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- nitric oxide release, subcutaneous implants, foreign body reaction, diazeniumdiolates, chronic inflammation, CD31, angiogenesis, implantable sensors, implant-tissue interface
- MeSH terms
- Animals, Dose-Response Relationship, Drug, Drug Carriers, Drug Implants, Foreign Bodies, Male, Nitric Oxide, Rats, Sprague-Dawley, Implants, Experimental, Rats
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