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Influence of diabetes on the foreign body response to nitric oxide-releasing implants.

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Title: Influence of diabetes on the foreign body response to nitric oxide-releasing implants.
Authors: Soto, Robert J.1, Merricks, Elizabeth P.2, Bellinger, Dwight A.2, Nichols, Timothy C.2, Schoenfisch, Mark H.1 schoenfisch@unc.edu
Source: Biomaterials. Mar2018, Vol. 157, p76-85. 10p.
Subjects: Diabetes, Foreign bodies, Therapeutic use of nitric oxide, Streptozotocin, Neovascularization, Laboratory swine
Abstract: The foreign body response (FBR) to nitric oxide (NO)-releasing subcutaneous implants was compared between healthy and streptozotocin-induced diabetic swine by evaluating inflammation, collagen capsule formation, and angiogenesis. Steel wire substrates were first modified with polyurethane membranes capable of diverse NO-release kinetics (NO fluxes and release durations of 0.8–630.0 pmol cm −2 s −1 and 2–13 d, respectively). The NO-releasing materials were implanted in the subcutis for 3, 10, or 25 d for histological and immunohistochemical evaluation of the FBR. A delayed, more severe inflammatory response to control (i.e., non-NO-releasing) implants was observed in diabetic pigs relative to healthy swine. Regardless of the animal disease state, each NO-releasing implant tested elicited reduced inflammation compared to controls at both 3 and 10 d. However, only the NO-release materials capable of releasing low NO fluxes (0.8–3.3 pmol cm −2 s −1 ) for 7–13 d durations mitigated the inflammatory response at 25 d. Using immunohistochemical staining for the endothelial cell surface marker CD-31, we also observed poor blood vessel development at non-NO-releasing implants in diabetic swine. Relative to controls, NO-releasing implants with the longest NO-release duration (13 d) increased blood vessel densities by 47.1 and 70.4% in the healthy and diabetic pigs, respectively. In the healthy model, tissues surrounding the long NO-release materials contained sparse amounts of collagen, whereas implants with shorter NO-release durations (2, 3, and 7 d) were characterized with a dense collagen encapsulation layer, similar to controls. Collagen deposition in diabetic swine was inhibited, and unaffected by NO. These results emphasize several key differences in the FBR in the setting of acute onset diabetes. The observation that NO release counteracts the more severe FBR in diabetic swine while simultaneously promoting tissue integration may help guide the design of medical implants (e.g., glucose sensors) with improved performance for diabetes management. [ABSTRACT FROM AUTHOR]
Copyright of Biomaterials is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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DbLabel: Engineering Source
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PubType: Academic Journal
PubTypeId: academicJournal
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  Data: Influence of diabetes on the foreign body response to nitric oxide-releasing implants.
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  Data: <searchLink fieldCode="AR" term="%22Soto%2C+Robert+J%2E%22">Soto, Robert J.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Merricks%2C+Elizabeth+P%2E%22">Merricks, Elizabeth P.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Bellinger%2C+Dwight+A%2E%22">Bellinger, Dwight A.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Nichols%2C+Timothy+C%2E%22">Nichols, Timothy C.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Schoenfisch%2C+Mark+H%2E%22">Schoenfisch, Mark H.</searchLink><relatesTo>1</relatesTo><i> schoenfisch@unc.edu</i>
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  Data: <searchLink fieldCode="JN" term="%22Biomaterials%22">Biomaterials</searchLink>. Mar2018, Vol. 157, p76-85. 10p.
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  Data: <searchLink fieldCode="DE" term="%22Diabetes%22">Diabetes</searchLink><br /><searchLink fieldCode="DE" term="%22Foreign+bodies%22">Foreign bodies</searchLink><br /><searchLink fieldCode="DE" term="%22Therapeutic+use+of+nitric+oxide%22">Therapeutic use of nitric oxide</searchLink><br /><searchLink fieldCode="DE" term="%22Streptozotocin%22">Streptozotocin</searchLink><br /><searchLink fieldCode="DE" term="%22Neovascularization%22">Neovascularization</searchLink><br /><searchLink fieldCode="DE" term="%22Laboratory+swine%22">Laboratory swine</searchLink>
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  Data: The foreign body response (FBR) to nitric oxide (NO)-releasing subcutaneous implants was compared between healthy and streptozotocin-induced diabetic swine by evaluating inflammation, collagen capsule formation, and angiogenesis. Steel wire substrates were first modified with polyurethane membranes capable of diverse NO-release kinetics (NO fluxes and release durations of 0.8–630.0 pmol cm −2 s −1 and 2–13 d, respectively). The NO-releasing materials were implanted in the subcutis for 3, 10, or 25 d for histological and immunohistochemical evaluation of the FBR. A delayed, more severe inflammatory response to control (i.e., non-NO-releasing) implants was observed in diabetic pigs relative to healthy swine. Regardless of the animal disease state, each NO-releasing implant tested elicited reduced inflammation compared to controls at both 3 and 10 d. However, only the NO-release materials capable of releasing low NO fluxes (0.8–3.3 pmol cm −2 s −1 ) for 7–13 d durations mitigated the inflammatory response at 25 d. Using immunohistochemical staining for the endothelial cell surface marker CD-31, we also observed poor blood vessel development at non-NO-releasing implants in diabetic swine. Relative to controls, NO-releasing implants with the longest NO-release duration (13 d) increased blood vessel densities by 47.1 and 70.4% in the healthy and diabetic pigs, respectively. In the healthy model, tissues surrounding the long NO-release materials contained sparse amounts of collagen, whereas implants with shorter NO-release durations (2, 3, and 7 d) were characterized with a dense collagen encapsulation layer, similar to controls. Collagen deposition in diabetic swine was inhibited, and unaffected by NO. These results emphasize several key differences in the FBR in the setting of acute onset diabetes. The observation that NO release counteracts the more severe FBR in diabetic swine while simultaneously promoting tissue integration may help guide the design of medical implants (e.g., glucose sensors) with improved performance for diabetes management. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Biomaterials is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1016/j.biomaterials.2017.11.044
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      – Code: eng
        Text: English
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    Subjects:
      – SubjectFull: Diabetes
        Type: general
      – SubjectFull: Foreign bodies
        Type: general
      – SubjectFull: Therapeutic use of nitric oxide
        Type: general
      – SubjectFull: Streptozotocin
        Type: general
      – SubjectFull: Neovascularization
        Type: general
      – SubjectFull: Laboratory swine
        Type: general
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      – TitleFull: Influence of diabetes on the foreign body response to nitric oxide-releasing implants.
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            NameFull: Soto, Robert J.
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            NameFull: Merricks, Elizabeth P.
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            NameFull: Bellinger, Dwight A.
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            NameFull: Nichols, Timothy C.
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              Text: Mar2018
              Type: published
              Y: 2018
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