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Nitric Oxide Signaling Pathway

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Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure...

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Nitric oxide release from a biodegradable cysteine-based polyphosphazene.

Alec Lutzke¹, Bella H Neufeld, Megan J Neufeld

¹Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA. Melissa.Reynolds@colostate.edu.

Journal of Materials Chemistry. B

|April 9, 2020

Summary

This summary is machine-generated.

This study introduces a novel nitric oxide (NO)-releasing polyphosphazene biomaterial. The new material demonstrates controlled NO release and shows promise for biomedical applications by not harming human cells.

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Combinatorial Synthesis of and High-throughput Protein Release from Polymer Film and Nanoparticle Libraries

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Area of Science:

Biomaterials Science
Polymer Chemistry
Medical Device Development

Background:

Nitric oxide (NO) is a crucial molecule with therapeutic effects, including antithrombotic and antimicrobial properties.
Incorporating NO-releasing capabilities into biomedical polymers can enhance implant performance and reduce complications.
Existing NO-releasing polymers are primarily polyesters, highlighting the need for novel materials with distinct characteristics.

Purpose of the Study:

To develop and characterize a new class of NO-releasing biodegradable polymer based on polyphosphazenes.
To investigate the synthesis and NO-releasing properties of a cysteine-based polyphosphazene.
To evaluate the cytocompatibility of the novel NO-releasing polyphosphazene for potential biomedical use.

Main Methods:

Synthesis of a thiolated polyphosphazene (POP-EtCys-SH) from poly(dichlorophosphazene) and ethyl S-methylthiocysteinate.
Conversion of thiol groups to S-nitrosothiol functional groups to create the NO-releasing polymer (POP-EtCys-NO).
Quantification of NO release under physiological conditions and assessment of cytotoxicity using human dermal fibroblasts.

Main Results:

The synthesized POP-EtCys-NO polymer exhibited an average NO content of 0.55 ± 0.04 mmol g⁻¹.
The polymer released a total of 0.35 ± 0.02 mmol NO g⁻¹ over 24 hours at 37 °C and pH 7.4.
Extracts from both thiolated and S-nitrosated polymers did not significantly affect fibroblast viability or morphology.

Conclusions:

A novel NO-releasing polyphosphazene (POP-EtCys-NO) was successfully synthesized and characterized.
The material demonstrates controlled nitric oxide release and good cytocompatibility with human dermal fibroblasts.
This cysteine-based polyphosphazene represents a promising candidate for advanced NO-releasing biomaterials in tissue engineering and other biomedical applications.