Chitosan is a biopolymer that has shown tremendous promise in the medical literature as an effective biomaterial for myriad biomedical applications, such as a hemostatic agent, immune adjuvant, drug delivery vehicle, tissue engineered scaffolds, and many more.1   However, its clinical use has been limited to mostly topical hemostasis due to difficulties in decontaminating chitosan for its use in human clinical settings.  Traditional standard techniques sterilization methods have been attempted to meet regulatory standards for implantation and/or injection of chitosan while maintaining its advantageous biological properties.2   But this have yet to be overcome until now.

An Ultra-Pure Ultra Clean Chitosan that’s sterile and endotoxin-free has been achieved with a new patented plasma-treatment technology.  This innovation overcomes the major barrier that has prevented use of chitosan in many biomedical applications due to the damaging effects of standard sterilization methods, such as harsh chemicals, gamma irradiation, dry or wet heat, and residual toxic compounds left after such methods.  This technology uses non-thermal atmospheric pressure nitrogen plasma for decontaminating chitosans from impurities, pyrogens, and especially endotoxins.  This now enables chitosan to be used in a wide-variety of medical applications from bench to market.

Chitosan (CS) is a biopolymer that continues to demonstrate greater potential for clinical use, as seen in the medical literature. This promise is due to CS’s many biofunctional capabilities, including but not limited to;

  • Biocompatibility
  • Hemostatic Agent
  • Biodegradeable
  • Immune Adujuvant
  • Bioadhesive
  • Tissue Engineered Scaffolds
  • Drug Delivery
  • And More…

However, CS’s clinical use has been limited due to its difficulties with there being a consistent and decontaminated CS product, and which meets regulatory standards while maintaining its many biological properties.  The contamination of chitosan can occur from a variety of places including;

  • The source of the starting material. For example, if shells used to produce chitosan are from shrimp that come from contaminated waters, unwanted residues of heavy metals and pyrogens, such as endotoxin may be found in the end CS product.
  • Contamination can also occur in the manufacturing process when process controls and assurances are not implemented sufficiently.

Historically chitosan sterilization methods involved harsh conditions that are required to inactivate tough microscopic contaminants and pathogens. These conditions alter the CS molecule being sterilized, causing a multitude of chemical, morphological, and mechanical changes.  These changes affect the biofunctions of the CS, and ultimately the application the CS is used in.  Conventional sterilization reduces chitosan molecular weight (Mw). For example, electron beam sterilization reduced the Mw of CS by 56%, and gamma irradiation induced main chain scissions in CS fibers, and films that decreased the Mw of CS by 25%.12,13 

Other challenges caused by traditional sterilization methods include chemical alterations of CS and residual toxic residues.14-18   Reduction in the Mw of CS reduces its adhesion strength to tissues by limiting chain flexibility for interpenetration and entanglement of tissue proteins and mucus.19   This effect is demonstrated by the failure of low-Mw CS to form a firm coagulum when exposed to blood in vitro.20   

Other factors that affect the bioadhesivity of CS, like degree of deacetylation and degree of ionization, also may reduce its hemostatic efficacy since it is postulated that CS induces
hemostasis via red blood cell agglutination and a ‘velcro-like’ adhesion to tissue surfaces.19,21

Plasma Technology

The technology is a patented non-thermal atmospheric pressure nitrogen plasma technology for decontamination of delicate biomaterials, such as chitosan.
Plasma is the fourth state of matter, after solid, liquid and gas. Lightning, the Northern Lights (aurora borealis), and the sun are natural examples of plasma. Artificial plasmas include arc-welders and fluorescent/neon lights. Gases become plasmas when a specific voltage is applied to a gas, which produces unique properties such as conductivity, magnetism, quasi-neutrality and high concentrations of ionized gas molecules and free radicals that are superb at destroying viruses, microbes, and endotoxins.

These are only a few reasons why researchers should consider the terminal sterilization CS in the initial stages of the R&D process.  The plasma-treatment technology overcomes this barrier, which will allow chitosan to be used in a wide-variety of medical applications.

References

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