Introduction

Various biomaterials have been successfully used in medical and dental research. It can be broadly classified in natural and synthetic. Most of the natural biomaterials are more effective than synthetic materials. The medicinal properties and human acceptance are better appreciated in natural biomaterials than synthetic materials. Research always has a greater focus on significant applications of natural biomaterials (Dutta, Dutta, Joydeep, & Tripathi, 2004).

Chitosan is an aminoglucopyran belonging to the linear polysaccharide family. It is commonly found in crustaceans and internal structure of invertebrates (Kumar, 2000). The chitin provides essential strength to the crustaceans and thus protects the organisms. Chitin was discovered in early 1800. The use of chitin was limited due to the complex structure, which was hard to make it soluble to common solvents (Husain et al., 2017). The discovery of chitosan by French scientist Charles Rouget in 1859, increased the chitosan applications (Kong, Chen, Xing, & Park, 2010). Unlike the rigid chitin structure, chitosan can be modified into various forms by dissolving it in various solvents and acids that increased its applications (Struszczyk & Struszczyk, 2007)

Structure

Chitin is a white, hard, nitrogenous polysaccharide and it the second most naturally occurring polysaccharide. It is composed of ß (1,4) 2 acetamido-2-deoxy ß -D glucose (N-acetyl glucosamine) (Dutta et al., 2004). Chitosan is a derivative of chitin and obtained by acetylation of chitin. It is made of N -acetylglucosamine and β-(1-4)-2-acetamido-2- deoxy-D-glucopyranose with acetylated amine groups (Kumar, 2000). Chitosan majorly contains 44.11% of carbon, 7.97% nitrogen ad 6.84% hydrogen. The chitin and chitosan are of greater interest, is because of the higher percentage of nitrogen when compared to other synthetic biomaterials.

Synthesis

Chitosan is majorly derived from chitin. Chitin is widely available in plants and animal kingdom. Chitin can be extracted from fungi, algae, lace animals, worms- round, horseshoe and in tendons of arthropods. Recent years the chitin and chitosan are obtained from discarded products of marine industry (Kong M., 2010). Chitin is available as three polymorphic state forms as alpha (∝) beta (β) and gamma (γ) chitin. The polymorphic forms vary in size, number of chain and degree of hydration (Cicciù, Fiorillo, & Cervino, 2019). The shells of crustaceans – crab, lobster, oyster, shell fish predominantly contains alpha chitin. beta and gamma chitins are found in squids and cuttlefish (M, 2017).

The synthesis of chitosan from these shells involves simplified process. The process of synthesizing chitosan can be broken down into stages of size reduction, deproteinization, discoloration, demineralization, depigmentation and deacetylation. The synthesis can be done either by chemical and enzymatic method (Dutta et al., 2004). The chemical synthesis is commonly followed where the Chitin is obtained by size reduction of shells into smaller particles (reduction), removal of protein (deproteinization), discoloration and dissolving calcium carbonates (demineralization) present in the shells. The resultant chitin is decolored and deacetylated in sodium hydroxide (deacetylation) to obtain chitosan. The synthesis can be done by different methods (Kumar, 2000). It is primarily synthesized by chemical method.

Properties of chitosan

Chitosan is a safe, non-toxic and biodegradable natural polymer. It has a linear polyamine chain with reactive amino and hydroxyl groups; it has the potential to chelate the translational metal ions. It possesses all properties of polysaccharides. The precursor of chitosan is chitin. Chitin is hydrophobic and insoluble in most of the organic solvents and water (Kumar, 2000). The deacetylation of chitin produces chitosan that improves the physical, chemical properties. The presence of amino- groups in chitosan improve the chemical properties when compared to chitin. Chitosan is hydrophilic. It is less soluble in neutral and alkaline pH.but soluble in many organic and inorganic acids (Husain et al., 2017). The degree of deacetylation and pH can alter the properties of chitosan (Struszczyk et al., 2007).

The biological properties of chitosan display more favourable outcomes; it has proven to be antibacterial, hemostatic, osteoconductive, fungistatic, antitumor, spermicidal, Immunoadjuvant and depressant of the central nervous system. Chitosan can bind easily with mammalian cells. It stimulates tissue and bone regenerations. Chitosan exhibited good cytocompatibility with fibroblasts, epithelial, endothelial, chondrocytes, hepatocytes, keratinocytes and myocardial cells. Chitosan can be quickly processed as sponges, scaffolds, beads, micro and nanoparticles make it a versatile material (Cicciù et al., 2019).

Modification

Efforts were made to generate functional derivatives of chitosan. Chitosan has three reactive functional groups which aid in increasing the applications. The hydroxyl groups at (C-6) and (C-3) and amino (C-2) of chitosan assist in chemical modification of chitosan. These groups are readily available for chemical reaction and salt formation with acids and other compounds. Glycerol chitin, N-phthaloylation of chitosan, Dendronized chitosan-sialic acid hybrids, methylthiocarbamoyl and phhenylthiocarbamoyl chitosans, Glycolic acid chitosan, chitosan triphosphate nanoparticles, chitosan beads, Chitosan esters, ZnO chitosan composites, Nanocomposites are some of the common modifications done to enhance its applications (Kong et al., 2010).

Uses of chitosan

The uses of chitosan can be broadly divided into industrial, biomedical and dental applications. The industrial applications involve its use in agriculture -seed, fertilizer coating, agrochemical release, surface treatment in paper manufacturing, body creams in cosmetics, food processing, water engineering, packaging material and textile industry. The non-toxic, antimicrobial, nonantigenic, bioactive, biodegradable and biocompatible properties of chitosan aid its use in biomedical and dental applications. Some of the biomedical applications are -:

Wound healing

Chitosan promotes wound healing. The studies have suggested that it accelerates wound healing by 30%. It has good antimicrobial and hemostatic properties makes it component of a wound dressing. Studies in the process to determine the effectiveness of coating the dressing material with chitin and chitosan. Conflicting data available in terms of promoting wound healing. More studies required to determine the efficacy of chitin/chitosan coating in wound dressing materials. The application of N-carboxymethyl chitosan to affected area enhanced wound healing and reduced scar formation (Mo, Cen, Gibson, Wang, & Percival, 2015).

Chitosan acetate has been effectively used in treating burn treatment. It aids in oxygen permeability which is most required in burn treatment to prevent oxygen deprivation of damaged burn tissues. The biocompatibility, biodegradability, and absorption of water make it an ideal material for burn management.

Contact lens

The mechanical strength, optical clarity, oxygen permeability, immunological compatibility, physical properties and water content makes it a material of choice for making contact lens (Mehta et al., 2019). Soon it shall replace the synthetic polymers in ophthalmic applications (Başaran & Yazan, 2012).

Tissue engineering

Tissue engineering involves the process of substituting the natural one with artificial tissues. The biocompatibility, biodegradability, polycationic nature, antimicrobial and functional properties of chitosan aid in playing the vital role in tissue engineering (Ahsan et al., 2018). Various studies displayed satisfactory responses when the materials were either seeded, grafted scaffolded with chitosan (Sultankulov, Berillo, Sultankulova, Tokay, & Saparov, 2019). The favourable cell attraction and attachment properties of chitosan that plays a critical role in tissue engineering, bone regeneration and nervous system. The significant among them is auricular repair, scaffolded tissue and bone regeneration (LogithKumar et al., 2016).

Drug delivery

In recent years the technology of sustained release of drug is considered a useful mode of treatment. The search exists on the drug delivery medium that can help in the sustained release of drugs in the target area (Ali & Ahmed, 2018). The functional amine, hydroxyl groups and the cationic charged particles make it a material of choice for protein carrier. This aids in as useful material of choice for drug delivery or drug carrier to produce a targeted effect and improve the drug efficacy. The initial tests have been promising, and more studies are done in varying fields (AL-Jbour, Beg, Gimbun, & Alam, 2019).

The reports suggest that chitosan aids in reducing cholesterol, supporting weight loss management (Ríos-Hoyo & Gutiérrez-Salmeán, 2016) enhancing the health of the patients in dialysis (Anraku et al., 2014), Crohn's disease (Iglesias et al., 2019), control of dental plaque, dental caries and periodontal infections (Bae, Jun, Lee, Paik, & Kim, 2006). More evidence is required to substantiate the results.

Dental applications

The chitosan has been extensively studied in dental applications (Narang & Narang, 2015) (Table 1). Chitosan composites have been effectively used as oral drug delivery systems. It was used effectively in many oral pathologies, to deliver antibiotics to periodontal tissues, oral mucositis. It has been effectively used as a muco-adhesive patch to prevent dental caries by sustained release of antibacterial medicaments. The use of chitosan in dentifrices and mouthwashes were effective in preventing the adhesion of microbes to the tooth, and additionally, the broad spectrum of antimicrobial properties inhibits the growth of pathogens (Schlueter, Klimek, & Ganss, 2013)

Chitosan displayed promising potentials in guided tissue and bone regeneration. The properties of chitosan aids in forming templates with conventional materials and aid in periodontal tissue and bone regeneration. The bio-integrative and conduction potential of chitosan provide excellent results in regenerations. The chitosan composites aid in producing functionally graded membrane scaffolds that be either layered, printed or cast for practical clinical use (Aguilar et al., 2019).

Chitosan had been effective in controlling the tooth-tissue loss when adding in the dentifrices and mouthwashes. The properties of affinity for binding, cationic properties and low pH aid in easy attachment with salivary pellicles and enamel. This aid in forming of multilayer protective organic matrix over the surfaces and protects the enamel and tooth in an acidic environment (Pimenta, Zaparolli, Pécora, & Cruz-Filho, 2012).

The studies displayed that the mechanical properties of GIC improved with the addition of chitosan. The flexural strength and the fluoride leach out the release of GIC has increased with the addition of chitosan (24) (Debnath et al., 2017). The protein release makes the GIC cement more pulp friendly. The in-vitro studies provide more encouraging results as regenerative endodontic and bioactive material (Ibrahim, Priyadarshini, Neo, & Fawzy, 2017).

The science of enamel/ dentin bonding has been successful and is on continuous development to avoid clinical difficulties (M, 2017). The problems persist with isolation, and inappropriate removal of smear layer affects the bonding. The studies used the antioxidant chitosan gels along with other constituents of adhesive systems. The results displayed superior shear bond strength than the conventional dentin bonding systems (Ururahy et al., 2017).

The repair or regeneration of enamel is a challenging process. Various chitosan-based preparations for delivering the organic amelogenin have been evaluated and proven successful in the enamel regeneration. Chitosan aids in drug delivery, and additionally, the antimicrobial properties support in additional protection from secondary caries (Kong et al., 2010).

Candida infections are common in long term denture users. Though many methods have been tried to control the infection, it is less effective (Herla, Boening, Meissner, & Walczak, 2019). The use of chitosan in denture base material or denture reliners have been effective in laboratory studies (Gondim et al., 2018). The anti-fungal and antimicrobial properties are useful in controlling the infections in complete denture patients (Lee et al., 2018). The in-vitro studies on the same are promising more trials are required for its clinical use. High molecular weight chitosan has been proven to be useful in disinfecting vinyl polysiloxane impression materials (Ismiyati & Dipoyono, 2017).

Implant coatings are done to enhance osteointegration; various materials have been tried, tested and proven (Takanche et al., 2018). More coating materials are tried for better and superior results. The coating of chitosan on implant alters the elastic modulus of titanium (Govindharajulu et al., 2017). It reduces the differences in properties between bone and titanium. It reduces the stress concentration at the interface and adds the antimicrobial properties, osteogenic potential and drug delivery properties of chitosan can be useful adjuvant (Kalyoncuoglu et al., 2018). This place a significant role in future. Recently chitosan is used as a medium in Stem cell-based regenerative therapeutics (Hsu et al., 2013) and treatment of dry mouth syndrome (Laffleur, Fischer, Schmutzler, Hintzen, & Bernkop-Schnürch, 2015).

Conclusions

Chitosan is one of the useful biomaterials with extensive applications. The natural origin and the various modifications for biological uses made it as the most useful materials. Among the challenges faced, it holds as a good material of choice for medical, dental and biomedical uses—the research developments aid in obtaining newer and better modifications of chitosan for extended applications. The review has listed some of useful properties and applications of chitosan.

Conflict of interest

The authors declare that they have no conflict of interest for this study.

Funding support

The authors declare that they have no funding support for this study.