Biomaterials - Chitosan

The Most Promising Biomaterial of 21st Century

What is a Biomaterial?

A Biomaterial is a substance that has been engineered to interact with biological systems for a medical purpose, either a therapeutic (treat, augment, repair or replace a tissue function of the body) or a diagnostic one. The performance and success of a medical device depend on the property of its key biomaterial ingredient. So, the selection of proper biomaterial plays a crucial role in the development and manufacturing of a medical device.

An ideal Biomaterial for medical devices should have features including: Bioactive, Biocompatible, Non-toxic, Non-corrosive, Bio-inert, Bio-adoptable and Sterilizable.

Biomaterials are grouped into four different classes as Polymers, Metals, Ceramics and Composites which can be utilized alone or in combination with each other to develop most of the commercially available medical devices. Biomaterials show promising activity in medical device development because of the ease of material fabrication, wide flexibility, and biocompatible nature as well as their broad range of electrical, mechanical, chemical and thermal behaviours.

Types of Natural Biomaterials

Chitosan

Collagen

Cellulose

Starch

Gelatin

Alginate

What is Chitosan?

Chitosan is considered as one of the most promising biomaterials of the 21st century on accounts of its versatile nature, excellent biodegradability, biocompatibility, antimicrobial activity, non-toxicity and wide applications. Chitosan is derived from Chitin, a second most abundantly available natural polymer after cellulose.

Chitin is naturally found in the exoskeleton of shellfish such as crabs and shrimps, and in the cell membranes of fungi, yeasts, and other microorganisms. Chitin is not soluble in dilute acids, whereas chitosan is soluble in dilute acids. 

Chitosan is primarily composed of glucosamine and N-acetyl glucosamine residues with a 1, 4-β-linkage. The presence of primary amines (-NH2) in chitosan gives it a net positive charge and is important for its biological properties.

Molecular structure of Chitosan

  • Currently, Chitosan is one of the most studied and frequently investigated biomaterials
  • When the Degree of De-Acetylation(DDA) and nitrogen content in chitin exceeds by 50% and 7% respectively then it is called chitosan
  • Crustacean waste is considered as a major source of chitosan for its commercial exploitation

Chitosan Facts

  • Chitosan is derived from Chitin. It was the first polysaccharide identified by scientists, even before the discovery of cellulose
  • Henri Braconnot isolated Chitin from mushrooms in 1811 for the first time
  • The name of ‘Chitin’ is derived from the  Greek word “Chiton” which means wrap.
  • In 1859, Prof C. Rouget heated Chitin in presence of an alkaline medium for the first time and discovered ‘Chitosan’
  • The word ‘Chitosan’ was coined by Hoppe-Seyler in 1894

Worldwide Distribution of Chitin and Chitosan in Nature

  • Chitin is naturally distributed in the endoskeleton of Cephalopoda, the exoskeleton of arthropods and the cell membrane of fungi and plants. 
  • Each year 6-8 million tons of Crustacean waste produced globally from the shells of shrimp, crab, lobster, and squid
  • Production of chitin from marine sources are identified in the countries such as India, China, Japan, Poland, Australia, the United States and Norway

Chitosan Extraction

The production of chitosan starts with the selection of a suitable source for chitin extraction. Chitin can be extracted from either the animal sources such as shellfish or non-animal sources such as fungi. The physicochemical properties of chitosan can vary greatly depending on its source.

Chitin is extracted from natural sources via De-mineralization and De-proteination. The purified Chitin is then treated with concentrated alkalis  (e.g. sodium hydroxide) to obtain Chitosan.

The process is known as De-acetylation and it affects the final properties of  Chitosan such as the extent of positive charge (proportion of amine groups in polymer) and molecular weight.

Chitosan Production

Types of Processed Chitosan

Chitosan is an extermely versatile Biomaterial. It can be processed into various forms such as Micro or Nano Fibers, Micro or Nano Gels, Beads, Films or Capsules, Sponges or Scaffolds, Micro or Nanoparticles, Hydrogel and Gauzes.

Chitosan Quality

Good Quality Chitosan

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1.Dispersion of Chitosan Powder in Water

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2. Addition of Acid

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3. Continuation of Stirring Process

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4. Chitosan powder getting dissolve

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5. Final Chitosan solution –Transparent and cleared viscous solution

Low Quality Chitosan

Presence of insoluble particles and impurities

Chitosan Powder

Chitosan Powder

Chitosan Flakes

Differentiate based on parameters including

  • Physical apparency and purity against low-quality chitosan
  • Molecular weight, viscosity, and DDA value

Physiochemical characterization of Chitosan

Chitosan Categories based on DDA Value

Factors affecting DDA of Chitosan

Factors Affecting DDA of Chitosan

Significance of DDA in Chitosan

Chemically, Chitosan is a derivative of chitin, consisting of glucosamine and N-Acetylglucosamine chains, and is derived mainly from the endoskeleton of cephalopods, exoskeleton of arthropods and cell membrane of fungi and plants.

Removal of acetyl groups from chitin is described as the process of De-acetylation. Degree of De-acetylation evaluates the content of free amino groups in the molecular structure of chitosan.

When the number of acetamide groups or degree of De-acetylation is more than 50% (ideally 70-90 %) the polymer considered as a chitosan molecule. So, it plays an important role in differentiating between Chitosan and Chitin.

Commercially available chitosan has a wide range of degrees of De-acetylation value. The value of DDA in chitosan varies from 56% to 99% and Chitin with a % DDA = 75 or above is known as chitosan(No and Meyers, 1995).

DDA Measurement Techniques for Chitosan

Impact of DDA on Chitosan

DDA is considered a key factor for chitosan molecule as it strongly influences the biological and physicochemical properties. It impacts:

Factors Affecting the Viscosity of Chitosan

The intrinsic viscosity of 1% chitosan varies from 40 to 5000 cPs depending on several factors.

ASTM Test Methods for Chitosan

S No.Test MethodASTM No.
1Standard Guide for Characterisation and testing of Chitosan Salts as Starting Materials intended for use in Biomedical and Tissue-Engineered Medical Product ApplicationsASTM F2103 - 18
2Standard Test Method for Determining Degree of Deacetylation in Chitosan Salts by Proton Nuclear Magnetic Resonance(1H NMR) SpectroscopyASTM F2260 - 18
3Standard Test Method for Determining the Molar Mass of Chitosan and Chitosan Salts by Size Exclusion Chromatography with Multi-angle Light Scattering Detection (SEC MALS)ASTM F2602 - 18

Properties of Chitosan

Chitosan has been extensively studied as a Biomaterial for various applications. Some of its key properties are listed in this image. Due to its Biodegradable and Biocompatible nature, Chitosan has been used in both external as well as implantable medical devices.

As a fat binder, it has been used as a weight-loss agent. The mucoadhesive and viscosity modifying properties make it useful for drug delivery. The hemostatic, anti-microbial, anti-inflammatory, and analgesic properties make it an excellent wound management material.

Mechanisms of important properties of Chitosan

PROPERTYMECHANISM
HemostasisCationic chitosan binds to negatively charged blood cells and leads to platelet activation.
Anti-microbialPositively charged chitosan molecules bind to negatively charged microbial cell membranes, which leads to the disruption of microbial membrane, and subsequently the leakage of proteinaceous and other intracellular constituents.
Pain controlChitosan relieves pain through its analgesic effect by reducing concentration of inflammatory mediators (bradykinin) at site of injury. It also absorbs of proton ions released in the inflammatory site to control pain.
Wound healingChitosan helps in wound healing through multiple pathways such as, polymorphonuclear cell activation, Fibroblast activation, Cytokine production, Giant cell migration and Stimulation Of type IV collagen synthesis.
Scar preventionChitosan reduces the production of TNF-ß1&2, which are responsible for scarring. Collagen produced in presence of chitosan is fine reticulin-like fibrils rather than mature bands of dense collagen.

Applications of Chitosan

Chitosan has potential to be a game-changer  in the field of advanced wound care, pharmaceuticals and cosmetic industry

Wound Care

Cosmetics

Pharmaceuticals

Key Sections for Biomedical Applications of Chitosan

Bleeding control & Wound Healing

Disease Diagnosis & Implants

Tissue Engineering & Stem cell Technology

Drug Delivery & Gene Therapy

Wound Healing

How Does Chitosan Help in Wound Management?

REFERENCES

  1. Choi, C., Nam, J.P. and Nah, J.W., 2016. Application of chitosan and chitosan derivatives as biomaterials. Journal of Industrial and Engineering Chemistry, 33, pp.1-10.
  2. Cheung, R.C.F., Ng, T.B., Wong, J.H. and Chan, W.Y., 2015. Chitosan: an update on potential biomedical and pharmaceutical applications. Marine drugs, 13(8), pp.5156-5186.
  3. De Queiroz Antonino, R.S.C.M., Lia Fook, B.R.P., de Oliveira Lima, V.A., de Farias Rached, R.Í., Lima, E.P.N., da Silva Lima, R.J., Peniche Covas, C.A. and Lia Fook, M.V., 2017. Preparation and characterization of chitosan obtained from shells of shrimp (Litopenaeus vannamei Boone). Marine drugs, 15(5), p.141.
  4. Ibrahim, H.M. and El-Zairy, E.M.R., 2015. Chitosan as a biomaterial—structure, properties, and electrospun nanofibers. Concepts, compounds and the alternatives of antibacterials, pp.81-101.
  5. Pogorielov, M.V. and Sikora, V.Z., 2015. Chitosan as a hemostatic agent: current state. European Journal of Medicine. Series B, (1), pp.24-33.
  6. Dai, T., Tanaka, M., Huang, Y.Y. and Hamblin, M.R., 2011. Chitosan preparations for wounds and burns: antimicrobial and wound-healing effects. Expert review of anti-infective therapy, 9(7), pp.857-879.
  7. Anjum, S., Arora, A., Alam, M.S. and Gupta, B., 2016. Development of antimicrobial and scar preventive chitosan hydrogel wound dressings. International journal of pharmaceutics, 508(1-2), pp.92-101.
  8. Yuan, Y., Chesnutt, B.M., Haggard, W.O. and Bumgardner, J.D., 2011. Deacetylation of chitosan: material characterization and in vitro evaluation via albumin adsorption and pre-osteoblastic cell cultures. Materials, 4(8), pp.1399-1416.
  9. Aranaz, I., Acosta, N., Civera, C., Elorza, B., Mingo, J., Castro, C., Gandía, M.D.L.L. and Heras Caballero, A., 2018. Cosmetics and cosmeceutical applications of chitin, chitosan, and their derivatives. Polymers, 10(2), p.213.
  10. Sultankulov, B., Berillo, D., Sultankulova, K., Tokay, T. and Saparov, A., 2019. Progress in the development of chitosan-based biomaterials for tissue engineering and regenerative medicine. Biomolecules, 9(9), p.470.

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