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Nitric oxide-releasing semi-crystalline thermoplastic polymers: preparation, characterization and application to devise anti-inflammatory and bactericidal implants.

ABSTRACT: Semi-crystalline thermoplastics are an important class of biomaterials with applications in creating extracorporeal and implantable medical devices. In situ release of nitric oxide (NO) from medical devices can enhance their performance via NO's potent anti-thrombotic, bactericidal, anti-inflammatory, and angiogenic activity. However, NO-releasing semi-crystalline thermoplastic systems are limited and the relationship between polymer crystallinity and NO release profile is unknown. In this paper, the functionalization of poly(ether-block-amide) (PEBA), Nylon 12, and polyurethane tubes, as examples of semi-crystalline polymers, with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) within, is demonstrated via a polymer swelling method. The degree of crystallinity of the polymer plays a crucial role in both SNAP impregnation and NO release. Nylon 12, which has a relatively high degree of crystallinity, exhibits an unprecedented NO release duration of over 5 months at a low NO level, while PEBA tubing exhibits NO release over days to weeks. As a new biomedical application of NO, the NO-releasing PEBA tubing is examined as a cannula for continuous subcutaneous insulin infusion. The released NO is shown to enhance insulin absorption into the bloodstream probably by suppressing the tissue inflammatory response, and thereby could benefit insulin pump therapy for diabetes management.

SUBMITTER: Wang X

PROVIDER: S-EPMC6246781 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Nitric oxide-releasing semi-crystalline thermoplastic polymers: preparation, characterization and application to devise anti-inflammatory and bactericidal implants.

Wang Xuewei X Jolliffe Aaron A Carr Benjamin B Zhang Qi Q Bilger Mark M Cui Yu Y Wu Jianfeng J Wang Xianglong X Mahoney Mollie M Rojas-Pena Alvaro A Hoenerhoff Mark J MJ Douglas Justin J Bartlett Robert H RH Xi Chuanwu C Bull Joseph L JL Meyerhoff Mark E ME

Biomaterials science 20181101 12

Semi-crystalline thermoplastics are an important class of biomaterials with applications in creating extracorporeal and implantable medical devices. In situ release of nitric oxide (NO) from medical devices can enhance their performance via NO's potent anti-thrombotic, bactericidal, anti-inflammatory, and angiogenic activity. However, NO-releasing semi-crystalline thermoplastic systems are limited and the relationship between polymer crystallinity and NO release profile is unknown. In this paper ...[more]

PMID: 30328426

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Project description: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.

Dataset Information

Nitric oxide-releasing semi-crystalline thermoplastic polymers: preparation, characterization and application to devise anti-inflammatory and bactericidal implants.

Publications

Nitric oxide-releasing semi-crystalline thermoplastic polymers: preparation, characterization and application to devise anti-inflammatory and bactericidal implants.

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