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Table of Contents
REVIEW ARTICLE
Year : 2018  |  Volume : 5  |  Issue : 4  |  Page : 71-76

Chitosan hydrogel: Its applications in medicine and dentistry


1 Professor and Head, Department of Periodontology and Implantology, Daswani Dental College and Research Centre, Kota, Rajasthan, India
2 Post Graduate, Department of Periodontology and Implantology, Daswani Dental College and Research Centre, Kota, Rajasthan, India

Date of Web Publication29-May-2019

Correspondence Address:
Dr. Umang Jamwal
Department of Periodontology and Implantology, Daswani Dental College and Research Centre, Ranpur, Kota, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/INPC.INPC_2_19

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  Abstract 


Since times immemorial, there has been an interactive interdependence of man on nature. The world of technology has overpowered him, yet technology and nature go hand in hand to help mankind fulfill his day-to-day necessities. The developing civilization has once again led to a quest to turn to nature in search for materials that are ecofriendly and economical. Chitosan is one such polymer. The combination of properties of chitosan such as biocompatibility, biodegradability, nontoxicity, and antibacterial properties open many possibilities for its application in medicine and dentistry. This article overviews the applications of chitosan in the form of hydrogels that can be applied effectively and give promising results for target delivery of drugs, the reduction of toxicity, and its uses focused towards the advancement of dentistry.

Keywords: Chitosan, chitosan hydrogel, hydrogel


How to cite this article:
Singh G, Jamwal U. Chitosan hydrogel: Its applications in medicine and dentistry. Int J Prev Clin Dent Res 2018;5:71-6

How to cite this URL:
Singh G, Jamwal U. Chitosan hydrogel: Its applications in medicine and dentistry. Int J Prev Clin Dent Res [serial online] 2018 [cited 2019 Jun 20];5:71-6. Available from: http://www.ijpcdr.org/text.asp?2018/5/4/71/259260




  Introduction Top


Chitin is a natural, abundantly available aminopolysaccharide, cationic polymer, the building material that gives strength to exoskeletons of crustacean. Chitin has a rigid crystalline structure because of hydrogen interactions between hydroxyl and acetamide groups.[1] Pertaining to its rigid structure and poor solubility in aqueous solutions, it is not readily applicable.


  Chitosan Top


Alkaline deacetylation of insoluble chitin leads to formation of chitosan [Figure 1].[2] It is more useful than chitin as it possesses properties such as increased and enhanced biocompatibility and biodegradability and is a safe antimicrobial agent.
Figure 1: Conversion of chitin to chitosan

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  Mechanism of Action Top


  • There are different mechanisms that prove the versatility and antimicrobial activity of chitosan:


    1. The ionic surface interaction leading to wall cell leakage
    2. The inhibition of the mRNA and protein synthesis when chitosan penetrates the nuclei of the microorganisms
    3. The formation of a barrier that suppresses microbial growth.


  • The molecular weight as well as the degree of acetylation determines such activity. In general, the lower the molecular weight and degree of acetylation, the higher will be the effectiveness in reducing microbial growth [3]
  • Studies have shown chitosan [Figure 2] to have higher antibacterial activity against Gram-positive bacteria than Gram-negative bacteria. Chitosan binds to the negatively charged bacterial cell wall causing disruption of the cell leading to an alteration of the membrane permeability and inhibition of DNA replication that eventually leads to cell death. Chitosan selectively binds to trace metal elements causing toxin production and inhibiting microbial growth.
Figure 2: Raw chitosan flakes

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  Uses of Chitosan Top


  • Chitosan [Figure 3] has numerous applications in biomedical as well as pharmaceutical industries
  • Research is being carried out on chitosan and its derivatives for the purpose of tissue engineering, drug delivery, wound healing, water treatment, antitumor, and antimicrobial effects.
Figure 3: Chitosan powder

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Hydrogel

In the 1960s, the platform for hydrogel research was created by Wichterle and Lím.[4] They synthesized hydrogels based on the copolymerization of hydroxyl methacrylate and cross-linker ethylene glycol dimethacrylate. Since then, hydrogels have been extensively used in the fields of drug delivery, biosensing, and tissue engineering.[5] Hydrogels have a high capacity for water absorption. They have hydrophilic functional groups in their polymeric structure such as amine (NH2), hydroxyl [-OH], amide (-CONH-, -CONH2), and sulfate (-SO3 H).[6] These groups enable the hydrogel to absorb water that results in hydrogel expansion. “Swelling” of the cross-linked structure of hydrogels prevents the destruction of the hydrogel cross-links.[7] Cross-linking density, chemical structure of the polymers and environmental conditions [8] determine the amount of water absorption in different types of hydrogels.

Hydrogels have the capacity to carry small molecule drugs, proteins, growth factors, and other necessary components for cell growth and differentiation. They can be utilized to allocate drug concentration at the site of action and reduce side effects.[9] Some examples of polysaccharide-based hydrogels are hydrogels made of alginate cellulose chitin, chitosan dextran, hyaluronic acid pectin, starch, and xanthan gum. Synthetic polymers such as poly (vinyl alcohol), polyacrylamide, poly (ethylene oxide), and polyethylene glycol have been used for hydrogel formation.[10]

Natural polymers generally have higher biocompatibility compared to synthetic polymers, as they undergo biodegradation by human enzymes like lysozyme-producing biocompatible byproducts.[11] Synthetic polymers are chemically stronger than natural ones because of slower degradation rate [Figure 4]. This feature provides prolonged life time in human body.[12] Homopolymer hydrogels are cross-linked networks of one type of hydrophilic monomer unit. Copolymer hydrogels are produced by cross-linking of two comonomer units. Interpenetrating polymeric hydrogels are produced by preparing a first network that is then swollen in a monomer.[13]
Figure 4: Classification of hydrogels on the basis of their properties

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Chitosan hydrogel

Chitosan has been extensively used to prepare hydrogel systems. Depending on the pore size and connectivity, it can lead to cell differentiation and eventually tissue formation. They have been applied as delivery systems for the controlled release of drugs.

Polymers exert their mucoadhesive characteristics while interacting with opposite charges. This specific feature provides the ability to the tissue to bind for specific drug delivery.[14] To improve the versatility of chitosan for medical and pharmaceutical applications, several derivatives of chitosan such as 4-azidobenzoic acid, methyl acroloyl glycine and polyethylene glycol have been synthesized and studied such that it can adhere to negatively charged biological surfaces as a bioadhesive material. The use of chitosan prolongs the residence time of drug-loaded system and provides localized drug delivery.[15]


  Applications of Chitosan Hydrogel Top


Wound healing

  • Chitosan in topical form is used for wound healing by infiltrating the inflammatory cells such as polymorphonuclear leukocytes [16] and secretion of inflammatory mediators like tumor necrosis factor-α. There is also migration of macrophages and increase in the amount of collagen
  • The binding of N-acetyl-D-glucosamine to specific receptors in body increases macrophage activation that leads to release of biological mediators [17]
  • Chitosan activates the complement system [18] and stimulates fibroblasts to release interleukins and other cytokines.[19]


Oral drug delivery

  • Hydrogels can be used for drug delivery to oral cavity to suppress mouth diseases without the risk of first pass effect.[20] The hydrogels dispense drug delivery to specified sites.[21] They enfold the macromolecule drugs into their polymeric chains that protect them from fast dissolution and control release rate from matrices
  • Chitosan is nontoxic, stable, biodegradable, and can be sterilized. These properties make chitosan a versatile material for its application in the biomedical and biotechnological fields [22]
  • Chitosan and chitosan-based hydrogels are pH sensitivity and mucoadhesive. This results in significant drug release based on pH shifts by regulating the hydrogel-swelling response. Mucoadhesion, which refers to the ability of a material to bind to the mucus lining, is regulated by the affinity for the mucin glycoproteins of the mucus
  • The local delivery of therapeutics to the mouth can be used to treat a number of diseases such as periodontal disease, stomatitis, fungal and viral infections, and oral cavity cancers
  • Drug administration through the buccal mucosa in the mouth provides advantages such as avoidance of the hepatic first-pass metabolism [23] and the acidity and proteolytic activity of the rest of the GI tract. Quaternized chitosan can also be used as an antimicrobial in dental implants and an antimicrobial wound dressing material for surgery.[16]


Tissue engineering

  • Chitosan and its derivatives have been widely studied for tissue engineering biomaterials without producing toxic end products when the new tissues are formed. Chitosan-based biomaterials provide certain mechanical and structural properties for proper functioning of the repaired tissues [24]
  • They are porous in nature for diffusion of gases, nutrients, and metabolic wastes. There is increased surface area for cell attachment, migration, and differentiation. They can be easily molded into any shape and volume and provide temporary mechanical support.


Antitumor activity

  • Chitosan demonstrates antitumor activity in terms of a therapeutic agent and as a drug carrier. Its antitumor activity is related to its ability to induce cytokines production through increased T-cell proliferation. Tokoro et al.[25] observed that the antitumor effect of chitosan derivatives was due to the increase in secretion of interleukin-1 and 2 which caused maturation and infiltration of cytolytic T-lymphocytes. This study was supported by Lin SY et al[26] who demonstrated that chitosan elevated lymphokine production and proliferation of cytolytic T-lymphocytes
  • Other investigations showed that chitosan was involved in direct killing of tumor cells by inducing apoptosis.


Adsorption

  • Chitosan is regarded as one of the most effective materials for adsorption of pollutants in water treatment systems. Chitosan can act as a chelating agent by binding to toxic heavy metal ions. The presence of amino and hydroxyl groups in chitosan allows its adsorption interactions with pollutants such as dyes,[27] metals,[28] and organic compounds [29]
  • Chitosan modified with different derivatives offers a wide range of properties for specific adsorption of metal ions.[28] Nanochitosan adsorbents manifest specific characteristics such as high specific surface area, low internal diffusion resistance, low cost, ecofriendliness, and biodegradability that enable them to exhibit higher capacities for pollutants.


Obesity treatment

  • Chitosan is traded as a dietary supplement for lowering serum cholesterol and controlling obesity. Chitosan swells up giving the feeling of fullness by filling the stomach.[30] It is safe for consumption without any known side effects
  • It is not specifically digested in our gastrointestinal tract.


Antioxidant activity

  • Antioxidants are known for their beneficial effects on health. They protect the body cells from damaging effects of oxidation. Studies are being carried out to investigate the antioxidant activity of chitosan and its derivatives in recent years [31]
  • Park et al.[32] reported that low molecular weight chitosans are more active in scavenging free radicals, such as hydroxyl, superoxide, alkyl, and 2,2-diphenyl-1-picrylhydrazyl radicals.



  Treatment of Periodontitis Top


Chitosan was discovered in 1859 by Rouget by subjecting chitin to hot potassium hydroxide solution. In 1894, Gilson confirmed the presence of glucosamine in chitin. It was named chitosan by Hopper-Seyler.[33],[34] Since then, several studies and researches have been carried out to investigate the properties of this polymer and its derivatives.[35] For the treatment of chronic periodontitis, chitosan in the form of gel and hydrogel base in toothpastes, mouthwashes, and chewing gums is being used to reduce the number of Streptococcus mutans in the oral cavity [36],[37] Properties of chitosan such as bioactivity, anti-inflammatory, wound healing, hemostasis, and bone repair are being extensively studied to widen its scope in dentistry [Figure 5].
Figure 5: Application of chitosan in treatment of periodontitis

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Bioactivity

  • Investigations have proved chitosan as an antimicrobial agent effective against a wide range of microorganisms such as algae, bacteria, yeasts, and fungi.[38],[39] Chitosan and calcium phosphate mineral are bioactive. This property is enhanced by the functional and structural versatility of chitosan
  • It shows strong activity in reducing dental plaque and has proven in vitro antimicrobial activity against various pathogenic oral cavities directly involved in plaque formation and periodontal disease such as Actinobacillus actinomycetemcomitans, Streptococcus mutans, and Porphyromonas gingivali s.[39]


Wound healing and hemostasis

  • In vitro studies reveal that properties of chitosan are advantageous in treating different phases of wound healing. Chitosan affects specific cells, which are involved in the process of wound healing.[40],[41] Chitosan stimulates macrophages to release interleukin-1 that stimulates fibroblast proliferation. Chitosan in general releases acetylglucosaminidase N and enzymatic degradation and increases biosynthesis of hyaluronic acid and extracellular components related with scar formation.[38]


Anti-inflammatory

  • Chitosan is associated with the presence of N-acetyl-D- glucosamine that stimulates inflammatory cells such as macrophages, fibroblasts, and polymorphonuclear neutrophils [38]
  • Studies, carried out about effects of chitosan particles on pathogens in periodontal and gingival fibroblasts, have shown chitosan to be a favorable material in the treatment of inflammation in the periodontium.[42]


Bone repair

  • Due to increase in the number of invasive surgical treatments, in dentistry, it becomes mandatory to include new materials for bone repair techniques. The materials should shorten duration of treatments, reduce the size of scars, eliminate pain, and ascertain faster recovery of the patient [43],[44]
  • The biodegradability and biocompatibility of chitosan enable its application as a biomaterial for hard tissue repair using the principle of scaffolding in a bone substitute and replacement by natural bone
  • Chitosan chemical H-bond chains, cross-linkings, and NH2+ with negative tissues in the human body provide good stability to start new bone cells formation and in case of regeneration, an early stage of bone healing.[40] Studies have shown that chitosan activates osteoblasts and can increase osteogenesis. Thus, it helps in guided periodontal tissue regeneration.



  Conclusion Top


Over the years, man has been extracting the advantages from naturally occurring materials and combining them with active compounds, thus playing an important role in the world of regenerative medicine. Chitosan is a biocompatible and biodegradable biomaterial that can be modified easily. Due to its availability, low cost, and minimal risk of transmission of disease and immune rejection, chitosan and its derivatives have so far emerged as promising materials in the safe delivery of drugs. A thorough understanding of its properties and mechanism of action would further strengthen its existence and hence its use in the field of dentistry.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

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