Chitosan as a matrix of nanocomposites: A review on nanostructures, processes, properties, and applications

Chitosan is a biopolymer that is natural, biodegradable, and relatively low price. Chitosan has been attracting interest as a matrix of nanocomposites due to new properties for various applications. This study presents a comprehensive overview of common and recent advances using chitosan as a nanocomposite matrix

Available online 22 July 2021

0144-8617/© 2021 Elsevier Ltd This article is made available under the Elsevier license (http://www.elsevier.com/open-access/userlicense/1.0/)

Review

Chitosan as a matrix of nanocomposites: A review on nanostructures,

processes, properties, and applications

Angelo Oliveira Silva, Ricardo Sousa Cunha, Dachamir Hotza,

Ricardo Antonio Francisco Machado *

Department of Chemical and Food Engineering (EQA), Federal University of Santa Catarina (UFSC), 88040-900 Florian´opolis, SC, Brazil

A R T I C L E I N F O

Chemical compounds studied in this article:

Chitosan (PubChem CID: 71853)

Chitin (PubChem CID: 6857375)

Polylactic acid (PubChem CID: 612)

Poly (vinyl alcohol) (PubChem CID:11199)

Poly (ethylene oxide) (PubChem CID: 174)

Poly (ethylene glycol) (PubChem CID: 174)

Iron Oxide (PubChem CID: 6432052)

Silicon dioxide (PubChem CID: 24261)

Halloysite (PubChem CID: 56841936)

Zinc oxide (PubChem CID: 14806)

Keywords:

Chitosan nanocomposites

Nanotechnology

3D printing

Scaffolds

Electrospinning

A B S T R A C T Chitosan is a biopolymer that is natural, biodegradable, and relatively low price Chitosan has been attracting interest as a matrix of nanocomposites due to new properties for various applications This study presents a comprehensive overview of common and recent advances using chitosan as a nanocomposite matrix The focus is

to present alternative processes to produce embedded or coated nanoparticles, and the shaping techniques that have been employed (3D printing, electrospinning), as well as the nanocomposites emerging applications in medicine, tissue engineering, wastewater treatment, corrosion inhibition, among others There are several re-views about single chitosan material and derivatives for diverse applications However, there is not a study that focuses on chitosan as a nanocomposite matrix, explaining the possibility of nanomaterial additions, the inter-action of the attached species, and the applications possibility following the techniques to combine chitosan with nanostructures Finally, future directions are presented for expanding the applications of chitosan nanocomposites

1 Introduction

Polysaccharides (starch, cellulose, chitin, hyaluronate…) are natural

polymeric biomaterials commonly employed in many biotechnological

fields The use of biopolymers in life science is increasing due to their

advantages, such as high availability, biocompatibility, and

biodegrad-ability There is also the added advantage of being converted to a variety

of chemically or enzymatically modified derivatives for specific end uses

( Bakshi et al., 2020 ) One of the most versatile biomaterials is chitosan,

which finds potential application in food and nutrition,

pharmaceuti-cals, biotechnology, material science, agriculture, and environmental

protection ( Harish Prashanth & Tharanathan, 2007 )

Due to its biocompatible nature, chitosan and its derivatives are used

extensively in water and waste treatment, medicine, electrochemical

fields ( Riaz Rajoka et al., 2019 ) The versatile chitosan applications are

related to the 3B properties: biocompatibility, biodegradability, and

biomimetics ( Bakhshayesh et al., 2019 ; Rizeq et al., 2019 ) Fig 1 shows

the increased interest in chitosan materials and nanocomposites in the last years

With the advance of nanotechnological fields, organic and inorganic nanofillers have been tested to produce chitosan nanocomposites pre-senting improved mechanical, chemical, thermal, and barrier properties ( Jafari et al., 2016 ; Rodrigues et al., 2020 ) Despite all that effort, there

is not a work in literature that systematically reviews the nanostructure possibilities, and the related shaping processes required for the desired application Therefore, this work intends to fill this gap and present the coming trends and challenges regarding chitosan as a matrix of nanocomposites

This paper is organized into three main sections: chemical structure and synthesis of the chitosan matrix and specific nanofillers, the most common shaping routes that have been employed, and the chemical and biotechnological properties related to applications of chitosan nanocomposites

* Corresponding author

E-mail address: ricardo.machado@ufsc.br (R.A.F Machado)

Contents lists available at ScienceDirect Carbohydrate Polymers

journal homepage: www.elsevier.com/locate/carbpol

https://doi.org/10.1016/j.carbpol.2021.118472

Received 3 May 2021; Received in revised form 19 July 2021; Accepted 19 July 2021

2 Chitosan nanocomposites: structure and microstructure

2.1 Chitin and chitosan: chemical structure and synthesis

Chitin is a semi-crystalline homopolymer of β-(1 → 4)-linked N-

acetyl-D-glucosamine It is the second most abundant natural

biopolymer after cellulose ( Bakshi et al., 2020 ) Chitosan, a partially

deacetylated product of chitin, is a copolymer consisting of β-(1 → 4)-2-

acetamido-D-glucose and β-(1 → 4)-2-amino-D-glucose units, where the

structures of both substances are presented in Fig 2 ( Muanprasat &

Chatsudthipong, 2017 )

In Fig 2 , radicals R1, R2, and R3 correspond to hydrogen in plain

chitin and chitosan molecule Those surface groups led to the amino

(NH2) and hydroxyl groups (OH), responsible for chitosan organic

modifications with several possibilities producing polymeric derivatives

of these compounds ( Tharanathan & Kittur, 2003 )

Crab and shrimp shell exoskeleton wastes are the raw material

source of biomass for the industrial production of chitin and chitosan The chemical structure of the crustacean shell is composed of protein, inorganic salts, chitin, and lipids The synthesis process of chitosan comes from a deacetylation reaction from chitin from the biomass source The chemical deacetylation reaction and the overview produc-tion of chitosan are presented in Fig 3 Typically, the manufacturing process follows these unit operations ( Bakshi et al., 2020 ; Nasrollahza-deh et al., 2021 ; Riaz Rajoka et al., 2019 ):

• The raw material shells are washed, crushed, and ground to smaller sizes with demineralization of some components, such as calcium carbonate, by chemical extraction with dilute hydrochloric acid with stirring at room temperature

• After demineralization, deproteinization is performed by applying dilute aqueous sodium hydroxide solution Proteins can be recovered

by lowering the pH to 4.0 and then drying the precipitates

• An additional decolorization step may be incorporated to remove color In this step, chitin is extracted as the main input material for the production of chitosan

• Chitosan is obtained by deacetylation from the chitin obtained, again

in sodium hydroxide but in an environment without oxygen and sometimes by an enzymatic route The three key reaction parameters are alkali concentration, time, and temperature Those factors define the degree of deacetylation of the final material

Chitosan derivatives nanocomposites have earned high interest especially due to their distinctive physical and chemical properties ( Fig 4 ) Amine (NH2) and hydroxyl (OH) surface groups promote the formation of several inter and intramolecular hydrogen bonds, which allows the embedding of nanoparticles used as a filler Chitosan has been increasingly investigated as an eco-friendly, low-cost, sustainable, and renewable nanocomposite

2.2 Chitosan as a nanocomposite matrix

Besides the use of chitosan as a pure matrix biomaterial, with the advance of nanotechnology, chitosan can be coupled with several kinds

of nanostructures, either embedded into the bulk material or deposited

on the surface

Biopolymers, such as chitosan, as pure single materials may exhibit

1934 -1970 1971-1980 1981-1990 1991 -2000 2001-2010 2011-2 022

0

10k

20k

30k

40k

50k

60k

Year

Chitosan Chitosan + Matrix + Nanocomposites

Magnification of the publications

from 1934 to 1990

1934-1970 1971-19801981-199

0

0

100

200

300

400

500

600

700

800

Year

Chitosan

Fig 1 Number of publications with search entries: “chitosan” (green),

“chi-tosan” and “matrix” (yellow), “chi“chi-tosan” and “matrix” and “nanocomposites”

(red) Total number of publications: 62563 Search date: March 15,

2021 (Scopus)

(A)

(B)

Fig 2 Chemical structures of (A) chitin (R1 =H) and its derivatives; (B)

chi-tosan (R1 =H, R2 =H, R3 =H) and their derivatives

Adapted from Muanprasat and Chatsudthipong (2017)

• Wash

• Crush

NaOH

Crustacean Shell Demineralize Deproteinaze Chitin

Chitosan

HCl

Deacetylation

2

3

4

1

5

Fig 3 Schematic overview of the main stages of production of chitin

and chitosan

some major drawbacks such as poor mechanical strength, low thermal

stability, and poor barrier properties ( Bakshi et al., 2020 ) Inorganic and

organic compounds in the nanoscale size have been added to chitosan

either as a filler dispersed inside the whole matrix, and/or as a coating at the material surface ( Kankala et al., 2020 ) to outcome most of those structure drawbacks Several nanostructures of inorganic, organic, metallic, or semiconducting nature can be applied and dispersed as additives in chitosan, such as nanoparticles, nanosheets, nanorods, nanocapsules, nanowires, and nanofibers, as shown in Table 1 This chapter focuses on the addition of single nanostructures to chitosan before shaping, and shows the materials that are commonly employed, as well as the chemical modifications or reactions required Other recent engineering processes for insertions of nanostructures within chitosan will be discussed further

2.2.1 Nanofillers

The most common way to produce nanocomposites using chitosan as

a matrix is to blend the nanofillers in a solution with dissolved chitosan, cast the slurry, and let it dry at room temperature ( Priyadarshi & Rhim,

2020 ) In some cases, a former step of nanoparticle reduction is needed

by means of a reducing agent, which is added into the slurry ( Kim et al.,

2019 ) By this method, it is possible to disperse a nanostructured ma-terial or composite inside the whole chitosan matrix This approach is employed to promote better properties such as mechanical ( Esmaeili

et al., 2019 ), thermal ( Smirnova et al., 2019 ), barrier ( Jafari et al.,

2016 ), magnetical ( G´omez P´erez et al., 2020 ; Hasan et al., 2020 ), or to slow down the release of some active nanomaterial ( Mishra et al., 2017 ;

Tripathi et al., 2011 )

Nanoaddition of several compounds has been investigated such as organic nanostructures ( Marín-Silva et al., 2019 ; Smirnova et al., 2019 ), oxide ceramics ( Aziz, Brza, et al., 2019 ; Aziz et al., 2020 ), metallic nanoparticles ( Kim et al., 2019 ), alloys ( Nivethaa et al., 2017 ) or com-binations of these materials ( Mishra et al., 2017 ; Wu et al., 2019 ) Therefore, there is an extended group of possibilities regarding nanotechnological species applied together with chitosan as matrix material The interactions between the nanostructures and chitosan are aimed to provide a suitable shaping process or promote a desired physicochemical properties regarding some specific applications

2.2.2 Nanocoatings and nanofilms

There are some particular cases when the simple blending with nanostructures is not the most adequate way for producing chitosan

CHITOSAN NANOCOMPOSITES PROPERTIES

Insoluble in water and organic solvents Soluble in diluted acetic acid

Chelating and Complexing Ionic conductivity

Biocompatibility and Biodegradability Antimicrobial

Hydrophilic and Bioadhesive

Fig 4 Typical physical and chemical properties of chitosan-based nanocomposites

Table 1

Some nanomaterials applied as additives (fillers, coatings) in chitosan

nanocomposites

Nanoadditive Nanostructure Filler/

coating Dimensions (particle size/length)

in nm

References

Ag Nanoparticles/

nanowires Filler/ coating 20–100 (et al., 2019Aziz, Abdullah, ; Aziz

et al., 2020; Aziz, Brza, et al., 2019;

Kim et al., 2019;

Vunain et al.,

2016) Cellulose Nanocrystals Filler 100 (Marín-Silva et al.,

2019) Chitin Nanofibers Filler 50–500 (Jafari et al.,

2016)

Fe3O4 Nanoparticles Filler/

coating 9.5–124 (Chatrabhuti & Barra et al., 2020;

Chirachanchai,

2013;

Heidarinasab

et al., 2016) Nanoclay Nanoparticles Filler <100 (Rodrigues et al.,

2020) PVA Nanocapsules Filler 113 (Mishra et al.,

2017)

Pt Nanoparticles Filler 3–7 (Kankala et al.,

2020) SiO2 Nanocapsules/

nanoparticles Filler 6–50 (2020Dakroury et al., ; Wu et al.,

2019) ZnO Nanoparticles Filler ~100 (Priyadarshi &

Negi, 2017;

Rodrigues et al.,

2020) Graphene Nanosheets Filler/

coating <400 (2017Holder et al., ; Jia, Gai,

et al., 2016)

nanocomposites Having the nanostructure only at the surface of the

chitosan matrix sometimes can be necessary, e.g to promote an easy

releasing or leaching of the nanospecies ( Chimisso et al., 2020 )

Chitosan has the chemical ability to form complexes with transition

metals and post-transition ions ( Priyadarshi & Rhim, 2020 ) Positively

or negatively charged nanostructures in the solution can easily

elec-trostatically bind or assembly with chitosan using the layer-by-layer

approach Zhou and Fu (2020) made a flame retardant wood attaching

wood, chitosan, phthalate, and metallic nanoparticles by controlling the

pH of each species solution Chitosan, which tends to be positively

charged in acidic conditions was bound at the wood surface Additions

of phthalate solution that is negatively charged followed, and further

phthalate with positively charged nanoparticles of TiO2 and ZnO were

added

De Mesquita et al (2010) have studied a layer-by-layer deposition of

chitosan and cellulose nanowhiskers producing a new biodegradable

nanocomposite The authors discussed that the use of this technique

maximized the interaction between both components and allowed the

incorporation of a high amount of nanofillers

Controlling the polyelectrolyte ions is essential to stabilize the

nanomaterial's surface when added to the chitosan matrix The

intro-duction of metallic nanoparticles into polyelectrolyte multilayers has

already proven to be achievable and promising

Silver nanoparticles (AgNPs) and other noble metallic nanoparticles

can also be introduced in the chitosan matrix, due to the affinity in the

structure toward Ag+ions, which is related to the amine and hydroxyl

groups ( Kumar et al., 2020 ) This kind of reaction can let the material at

the surface of the nanocomposite

To deposit the macromolecules on the chitosan surface, a chemical covalent modification of its structure is eventually necessary, especially

to allow the immobilization of the functional biopolymer/network The surface may be modified by the introduction of functional groups that can react with the polymer/nanostructure that has to be attached ( Chimisso et al., 2020 ) Chitosan presents amine (NH2) and hydroxyl (OH) radical groups that can enhance covalent or protonation reactions

as shown in Fig 5 The molecules applied can be used for nanoparticle chemistry stabilization at the surface ( Erathodiyil & Ying, 2011 ) For example, the chitosan-modified graphene oxide nanosheet can

be shaped by covalent conjugation of the amide linkage between the carboxylic groups of graphene and the amine groups of chitosan ( Jia, Gai, et al., 2016 ) To maintain the suspension stability of magnetic nanoparticles with chitosan, the covalent bond is more stable compared

to other forces ( Chatrabhuti & Chirachanchai, 2013 ) The epoxide opening reaction was performed by Heidarinasab et al (2016) to attach magnetic nanoparticles, and provide the best conditions for the mag-netic nanocarrier delivery

3 Manufacturing processes

3.1 Mixing and shaping

For the nanocomposites production, some considerations have to be taken into account to assure complete mixing of chitosan with the nanoadditives and solvents ( Riaz Rajoka et al., 2019 ) According to the chitosan solubility, a film formation can be either more easily performed

or become a difficult task ( Sampath et al., 2016 )

Fig 5 Examples of typical covalent grafting functionalization in chitosan at the chemical amino (NH2) and hydroxyl (OH) radicals

Based on concepts from Erathodiyil and Ying (2011)

Chitosan possesses a mild organic base structure behavior, capable to

produce salts in contact with weak acids The most common

experi-mental practice is to add small fractions of acetic acid in water to a

chitosan suspension so that salt formation and dissolution occur

concurrently ( Roberts, 1992 ) Chitosan has a high hydrophilic behavior

and for that reason, it is practically insoluble in organic solvents,

although some organic solutions of chitosan in aqueous acetic acid can

tolerate the addition of large volumes of polar solvents without causing

precipitation of the polymer ( John et al., 2019 ; Roberts, 1992 ) This kind

of chemical nature was very helpful for the chitosan nanocomposite

preparation by John et al (2019) In this case, the presence of ethanol in

the solvent mixture chitosan/water in acetic acid promoted adequate

TiO2 nanoparticle nucleation and film formation

Most of the studies about chitosan nanocomposites dispersion have

used simple magnetic mixing ( Priyadarshi & Rhim, 2020 ) Some works

employed more effective dispersion equipment like mechanical stirrer

with ultrasonication ( Celebi & Kurt, 2015 ) Some particular cases used

stronger mixing devices such as ultraturrax ( Marín-Silva et al., 2019 )

The main shaping technique for most of those nanocomposite systems

consists of a solution or solvent casting method ( Bakshi et al., 2020 )

which is the production of a dispersion phase in acetic acid, followed by

evaporation or a drying step ( Martínez-Camacho et al., 2010 )

3.2 3D printing

Three-dimensional nanostructured composites have become a high

interest in numerous fields including biomedical engineering, energy

storage, and structural or functional materials ( Sommer et al., 2017 )

Additive manufacturing (AM), commonly known as 3D printing (3D), is

a compilation of techniques comprising non-biological and biological

approaches production of a physical object from a three-dimensional

model, where the most common routes for chitosan nanocomposite

derivatives are presented in Table 2

The 3D printing techniques allow an elevated control of the

geom-etry of any manufactured biological structure, that accurately

corre-sponds to a computer-aided design (CAD) project ( Elviri et al., 2017 ) An

example is a 3D system developed by Elviri et al (2017) which

corre-sponds to a simple, safe, and low-cost process avoiding the use of organic

solvents, the need for high processing temperature, or the difficulty in

the removal of dust, which is very typical of analogous techniques of

additive manufacturing To be used in in vivo studies, the 3D printed

scaffold also should not lose its shape and strength after being soaked in

water for a long time ( Gang et al., 2019 )

Advanced biological scaffolds for tissue engineering can be easily

fabricated using a 3D printing technique, for example, robocast-assisted

deposition as tested by Cebe et al (2020) Their work with a robocaster

allows precise control of micropatterning by determining the

di-mensions of filaments, the size and shape of pores, and the percentage of

porosity of the scaffold

Bioinks are the common raw materials used in a 3D printer for

bio-logical applications ( Sahranavard et al., 2020 ) For practical

applica-tions, printability, fidelity, viscoelasticity, shear-thinning, yield stress,

creep, shelf life, cross-linking time, and cost are some of the essential

parameters associated with the selection of compounds for bioinks ( Lee

& Yeong, 2016 ) According to the applications, bioinks can be either supporting or functional The most commonly supporting bioink is a

hydrogel; a functional bioink (e.g., DNA and factor) is mainly used to

study intracellular delivery, gene diagnosis, and cell behaviors Chitosan is one of the best 3D printing matrix bioink candidates due

to its desirable physicochemical properties and essential features for cell adhesion, extracellular matrix (ECM) deposition, and finally tissue regeneration ( Jiankang et al., 2009 ) However, the chitosan matrix presents a common drawback characteristically of hydrogels, which is a weak mechanical resistance ( Whyte et al., 2019 ) For that reason, it is usually blended or coated with other materials, including nano-materials, to improve mechanical properties ( Semba et al., 2020 )

Sommer et al (2017) developed a modified oil-in-water emulsion con-taining chitosan with modified silica nanoparticles in the water phase The resulting ink provided good stability for the emulsion, and it was ideal for 3D printing and displayed high yield stress, storage modulus, and elastic recovery

Chitosan as a raw biomaterial for 3D printing is mostly processed using inkjet bioprinting approaches for bone implants and artificial skin applications ( Whyte et al., 2019 ) There has been an increased interest in 3D printing related to chitosan nanomaterials and their potential ap-plications in biomedical engineering including tissue engineering and medical implants ( Ahmed et al., 2020 ) Pahlevanzadeh et al (2020)

elaborated a concise review about 3D printable chitosan, both single and derivatives, aiming the development directions and prospect directions According to the authors, chitosan decomposes at typically lower tem-peratures, not higher than 220 ◦C, thus the nanomaterials employed in 3D printing techniques ought to be either sintered under this tempera-ture, or a corresponding thermoresistance should be promoted Never-theless, other limitations can be in a wide range considering the type of different methods, their performance strategy, and the desired application

Normally, 3D robust shaping techniques such as stereolithography (SLA), or Fused Deposition Modelling (FDM) are not possible with chi-tosan as the main material However, Seo et al (2020) have overcome that limitation for SLA printing In this case, 3D printing is based on photopolymerization by a laser, so that SLA requires a polymer that can

be photo-crosslinked, such as hydroxybutyl methacrylated chitosan (HBC-MA) HBC-MA was developed using chitosan as precursor mate-rial, which corresponds to a photocrosslinkable temperature-reversible chitosan derivative, reacting sensitively to temperature changes Cellu-lose nanofibrils were employed as nanoadditives being physically confined in the photocrosslinked hydrogel to assist in the directionally

of volume expansion, and swelling rate In conclusion, HBC-MA can be regarded as a potential material for tissue engineering, and medical applications

Limited by their difficult solubility and non-melting properties, chitosan 3D nanocomposites are hard to be directly manufactured by Fused Deposition Modelling (FDM) Although the use of chitosan as second material ( Yu et al., 2020 ), or single modification have been re-ported ( Elviri et al., 2017 ), until the present moment there is to the best

of our knowledge no printed chitosan nanocomposites fabricated by

Table 2

Comparison of some approaches for 3D printing chitosan derivative nanomaterials

Traditional manufacturing Solvent casting Material dissolved in a solvent Cannot be accurately

controlled (Bakshi et al., 2020) Additive manufacturing

(AM) Stereolithography (SLA) UV light or electron-beam is used to start a reaction Non-biological manufacturing (Seo et al., 2020)

Jet based printing Same principle that traditional inkjet printers Biological manufacturing (Ahmed et al., 2020; Sommer et al.,

2017) Laser-assisted

Adapted from Wang et al (2020)

FDM

The advancements in the two-photon direct laser writing (TDLW)

technique, a derivation of laser-assisted bioprinted, allowed the 3D

fabrication of complex polymeric structures Bozuyuk et al (2018)

fabricated chitosan derivative microswimmers by two-photon-based 3D

printing of a natural polymer derivative of chitosan in the form of a

magnetic polymer nanocomposite Amino groups presented on the

microswimmers are modified with doxorubicin employing a

photo-cleavable linker Chitosan imparts the microswimmers with

biocom-patibility, and biodegradability for use in a biological setting Their local

3D patterning has been performed with the use of versatile chemical

moieties and provided the possibility to embed nanoparticle additives

during the shaping step ( Bozuyuk et al., 2018 )

Another possibility for chitosan nanocomposites is by coating other

3D printed materials Azadmanesh et al (2021) performed an FDM

printing process with polylactic acid for scaffold production After the

3DP, chitosan and copper carbon dots (Cu-CDs) were cross-linked with

the PLA scaffolds This is an alternative approach to overcome the

dif-ficulties regarding chitosan physical and chemical properties

3.3 Electrospinning and electrospraying

The use of electrospinned and electrosprayed materials has expanded

in many important recent biotechnological fields such as food

technol-ogy, tissue engineering, drug delivery, and wound dressing ( Soares

et al., 2018 ) Electrospinning is a technique that aims to produce micro

and nanofibers mats from polymeric solutions or melt polymers ( Xue

et al., 2019 ) Commonly regarded advantages of materials and

com-posites made by electrospinning are high porosity, low pore size, and a

large surface area ( Chahal et al., 2019 )

In electrospinning, the charged polymer solution or melt overcomes

its surface tension under the action of a high-voltage electrostatic field to

form small jets, which are further accelerated and stretched, and finally

fall on the collector with solvent evaporation or melt cooling to form

fibers ( Haider et al., 2018 ; Yarin et al., 2001 ) Typically, a syringe

comprises an electrospinning shaping apparatus with a needle attached

to the syringe tip, which is directed to a metallic base acting as a support

for the fiber mat collection ( Haider et al., 2018 ; Yarin et al., 2001 )

The needle and the metallic base are connected to a high voltage

power source through electrodes An electrospinning device is generally

composed of a high-voltage power supply, a liquid supply device

(injector, etc.), and a collector (drum or metal plate, etc.) ( Araldi da Silva

et al., 2021 ) A typical device for electrospinning is presented in Fig 6

In the case of electrospraying, a process similar to electrospinning,

micro, and nanoparticles (spheres or capsules) can be obtained from a

polymer in solution with a high conductive solvent ( Soares et al., 2018 )

Producing chitosan nanofibers through the electrospinning process is quite challenging because of the material's ionic nature ( Cai et al.,

2016 ) The rigid structure prevents chain entanglements leading to the jet break up ( Kersani et al., 2020 ) In reason of that, most works prefer to bind with other polymers or biopolymers such as Poly(vinyl alcohol) (PVA) ( Koosha et al., 2019 ; Sedghi et al., 2017 ), Poly(ethylene oxide) (PEO) ( Kersani et al., 2020 ), Polylactic acid (PLA) ( Shan et al., 2014 ; Xu

et al., 2009 ), Polyethylene glycol (PEG) ( Han et al., 2011 )

Nanoparticles have been inserted before and after the electro-spinning process to improve material properties Halloysite and carbon nanotubes ( Koosha et al., 2019 ; Liu et al., 2019 ) and silica nanoparticles ( Zhao et al., 2015 ) have been added for enhancing mechanical behavior Silver nanoparticles ( Zhan et al., 2017 ) and Fe3O4 ( Cai et al., 2016 ) nanoparticles were also added to improve chitosan antimicrobial activity

There are few studies in the literature on the use of electrosprayed chitosan as the matrix material in nanocomposites Versatility and low- cost operation are some advantages that delineate a particular interest in this field ( Jayasinghe et al., 2006 ; Park et al., 2007 ; San Thian et al.,

2008 ) Chng et al (2019) allowed a controlled and precise deposition in dental implants that improved their properties, compared to conven-tional shaping techniques, since chitosan is a biopolymer that presents compatibility with biological systems, it has been used as a matrix after silane-based treatment to chemically bond the coated chitosan to the substrate, maximizing the adhesion strength between the coating and a surface Yuan et al (2019) produced microparticles containing chitosan and nano-hydroxyapatite (NanoHap), as well as pharmacological spe-cies These particles provided an effective way to long-term sustained release activity

3.4 Other techniques

As mentioned before, the main shaping technique for both chitosan and chitosan nanocomposites is the solution or solvent casting method ( Bakshi et al., 2020 ) This method consists of the production of disper-sion phase using commonly acetic acid, at high quantities, as solvent followed by evaporation or a drying step ( Martínez-Camacho et al.,

2010 ) This technique is limited to a specific material design structure (flat thin film deposited generally on a glass surface) generally as a final dense material ( Esmaeili et al., 2019 )

Moreover, chitosan is still also a natural-based polymer material and for that reason might be submitted to common polymer shaping pro-cesses such as thermoforming, injection molding, compression molding, rotational molding, extrusion, blow molding, among others Extruded chitosan nanocomposites were prepared successfully by Amouzgar et al (2017) and Choo et al (2016) In the first work, they studied the use of

15.0 kV

On Off

DC High Voltage

1.0 mL/h

Collector Polymeric Solution

DC High Voltage

0.5 mL/h

On/Off Volumetric Flow

Syringe Pump Polymeric Solution

On/Off Volumetric Flow

10.0 kV

Metal Collector

On Off

-Fig 6 Schematic view of typical nanofiber and nanoparticle manufacturing processes: (A) electrospinning and (B) electrospraying, respectively

chitosan with nanoactivated carbon; and in the second one, the selected

structures were halloysite nanotubes In both works, an additional

ul-trasonic dispersion was required for a successful extrusion process

There is no report until the present moment on the use of

thermo-forming, injection molding, rotational molding, compression molding,

and blow molding with chitosan nanocomposites In the case of blow

molding and rotational molding, no report was found on the use of

chitosan on this material as a matrix too However, injection molding,

thermoforming, and compression molding have been applied to the

single use of chitosan material or using chitosan as an additive in other

polymeric matrices

4 Chitosan nanocomposites: properties and applications

Due to all the application possibilities regarding chitosan

nano-composites, recent and important applications will be presented

Because of the material versatility, as seen in Fig 7 , the literature has

been focused on chitosan nanocomposites mainly in water and

waste-water treatment, tissue engineering, biomedical applications, and

corrosion inhibition

4.1 Waste and wastewater treatment

Waste and wastewater treatment is an important concern worldwide The necessity of access to quality potable water and effluents disposal has emerged in many material developments Chitosan both as a single material and as composites has gained significant interest in multilayer coatings for improving corrosion resistance ( Nasrollahzadeh et al.,

2021 ), and wastewater treatment ( Mohammadzadeh Pakdel & Peigh-ambardoust, 2018 ; Thirugnanasambandham et al., 2013 )

Crini et al (2017) described the use of chitosan in the process of ultrafiltration (UF) where a large variety of metal ions can be adsorbed and selectively separated Other authors also investigate and demon-strated good results using chitosan nanocomposites in heavy metal remediation ( Al-Sherbini et al., 2019 ; Cheraghipour & Pakshir, 2020 ;

Kenawy et al., 2019 )

Due to their chemical structure, chitosan nanomaterials have been employed in the removal of pollutants ( Nasrollahzadeh et al., 2021 ) such as heavy metal ions Cu(II) and Cr(VI) ( Anush et al., 2020 ), Cr (VI) ( Reis et al., 2021 ), Co (III) ( Abdelbasir et al., 2021 ), iron ( Shehap et al.,

2021 ), dyes ( Krishna et al., 2021 ; Mostafa et al., 2020a ; Rashid et al.,

2018 ; Rebekah et al., 2020 ; Reghioua et al., 2021 ; Sathiyavimal et al.,

2020 ), antibiotics and pesticides ( Asgari et al., 2020 )

The industrial use of organic dyes in many industries is environ-mentally hazardous, toxic, and carcinogenic Chitosan derivative nanocomposites emerge as a potential material to promote an efficient and sustainable dye removal ( Rashid et al., 2018 ) Recently, some research works have been studied according to the combination of different ceramic nanostructures or nanoclays with chitosan aimed to remove different types of organic dyes ( da Silva et al., 2021 ; Krishna

et al., 2021 ; Mostafa et al., 2020b )

The use of chitosan nanocomposites was explored by Asgari et al (2020) for antibiotic removal from wastewater Chitosan was tested together with Fe3O4 magnetic nanoparticles, which were capable to retain spontaneous metronidazole from water in industrial and hospital wastewater

The chitosan capability of binding semiconductors metals can create photocatalysts nanocomposites ( Huang & Peng, 2021 ) Those new nanomaterials can improve the quality of degradation of organic pol-lutants ( Midya et al., 2020 ) or dye removal by the Fenton process ( Ali-mard, 2019 )

The strong heavy metal adsorption capacity by chitosan and their derivatives can be related to multifunctional surface chemical groups, high hydrophilicity, high chemical reactivity, and polymer flexible structure ( Vunain et al., 2016 ) Gupta et al (2012) described charac-teristics of chitosan related to the polymer molecular chain, which contains plenty of amino and hydroxyl groups at the surface Those chemical groups can produce stables chelates binding with several metal ions, such as Hg2+, Ni2+, Cu2+, Pb2+, Zn+2, Cd+2 Zhu et al (2021) in a recent study emphasize that when chitosan is applied as an adsorbent directly, the specific surface area is modest, therefore the adsorption capacity is low Those properties effectiveness of single chitosan mate-rial can be effectively improved by shaping it into nanofibers However, other properties such as mechanical, stability, and reusability still de-mand to be further improved That lack of research might be fulfilled with the advanced knowledge in nanocomposites using chitosan as the matrix Furthermore, the majority of heavy metal adsorption research using chitosan is still on the laboratory scale, and it has some obstacles to their scale-up and practical implementation in the treatment of heavy metals present in industrial wastewater

4.2 Scaffolds for tissue engineering

Tissue and organ failures caused by injury, aging accounts, or dis-eases are an important concern worldwide ( Abbasian et al., 2019 ) Tissue engineering has become an important research field for clinical or biomedical applications regarding chitosan nanocomposites Chitosan is

Water and Wastewater treatment

Scaffolds and Tissue Engineering Clinical Applications

Corrosion Inhibition

Food Packaging

Energy Storage

DNA Extraction

Fig 7 Chart of distribution of chitosan nanocomposites applications in

this review

Table 3

Examples of chitosan porous materials and composites according to shaping

methods

Material/

composite Shaping Pore size (μm) Porosity (%) References

Chitosan Freeze-drying 60–90 88–97 (Nwe et al.,

2009) Freeze-drying and

Particulate leaching 7–500 60–90 (2011Lim et al., )

Liquid hardening 200–500 80 (Hsieh et al.,

2007) Gas foaming CO2 30–40 >30 (Ji et al.,

2011) 3D printing 3.5–9 52 (Intini et al.,

2018) Chitosan/

PLA Melt molding and NaCl leaching

>100 58.3–91.2 (Li et al.,

2004) Mold casting/

Infrared dehydration 0.2 Not informed (2009Xie et al., )

Chitosan/

PLGAa Electrospinning 0.5–2.5 >50 (Kim et al.,

2013) Chitosan/

NanoHap Freeze-drying 50–150

<80 (Ying et al.,

2020) Chitosan/

Nanoglass Freeze gelation 150–300 Not informed (et al., 2020Oudadesse )

aPoly lactic-co-glycolic acid

considered an ideal kind of material for use in tissue engineering mainly

due to its desired biological characteristics such as biocompatibility,

biodegradability, bioinertness ( Abinaya et al., 2019 ) Chitosan's

chem-ical structure can resemble major components of bone and cartilaginous

tissue, promoting cell adhesion ( Oudadesse et al., 2020 )

A particular area in tissue engineering, especially linked to chitosan

material is the production of scaffolds Scaffolds are porous materials

specially engineered to promote desirable cellular interaction, allowing

the formation of new functional tissues ( Whyte et al., 2019 )

The major difficulty related to scaffold design manufacturing is to

produce high porosity, controlled pore size, and pore interconnectivity

from natural-based polymeric raw materials Biobased materials such as

chitosan are heat sensitive, which limits the use of several scaffold

shaping techniques ( Sampath et al., 2016 ) Pure chitosan scaffolds with

controlled porosity are mainly produced for freeze-drying approaches or

combinations, although electrospinning has been increasingly employed

( Vandghanooni & Eskandani, 2019 )

Due to the chitosan possibility of chemical crosslink, the use of

chi-tosan composites with other synthetic biopolymers, such as PLA, and the

use of nanoparticles, such as nano-hydroxyapatite, broaden the chitosan

shaping possibilities ( Bulanov et al., 2020 ; Sampath et al., 2016 ) The

additives also must be specially selected, to maintain the

biocompati-bility from single chitosan ( Abbasian et al., 2019 ) Table 3 shows some

shaping techniques of chitosan materials and composites, used as porous

scaffolds for tissue engineering

In this context, Fig 8 shows a relationship between porosity and pore

size of chitosan materials, obtained through different shaping

tech-niques, as listed in Table 3 It is noted that, depending on the use of a

particular technique or combination of techniques, different porous

systems can be obtained, which shows the versatility of this raw

material

Therefore, the application of chitosan single or composite materials

in scaffolds for tissue engineering have been encouraged due to their

physical, chemical, and biological properties such as ( Vandghanooni &

Eskandani, 2019 )

• Cytocompatibility (in vitro or in vivo)

• Crosslinking to improve mechanical and barrier properties

• Mild processing conditions

• Antibacterial effect related to the chitosan cationic structure

• Excellent interactions with adhesive proteins and receptors

4.3 Other biomedical applications

Besides the use of chitosan scaffolds for tissue engineering, chitosan

as a single and composite nanomaterial has been studied in other related biomedical fields such as wound healing, drug delivery, dietary sup-plement, biosensors, among others Accordingly, chitosan has been applied to help to solve several human health issues: blood clotting, fast skin burn healing, food allergies and intolerance control, weight loss and cholesterol control, gene therapy, and cancer treatment, among others ( Rizeq et al., 2019 )

The most common pharmaceutical ability of chitosan was noticed especially inside fat and cholesterol-burning supplements, throughout the material ability to reduce weight gain by electrostatically attach to fatty acids released by digestion in the small intestine ( Shariatinia,

2019 ) May et al (2020) explained the chitosan mechanism during the digestion of full cream milk, they noticed that the lipids present self- assembled into characteristics stable liquid crystalline nanostructures However, a presence of a high concentration of chitosan was able to reduce fatty acids and prevent the self-assembly of lipids

In some conditions, chitosan can be suitable for the wound healing process due to antimicrobial properties linked with low mammalian cell toxicity ( Matica et al., 2019 ) For external skin wound healing, a nanocomposite containing silver nanoparticles and chitosan was tested

by Ding et al (2017) The film material needed to attach over the skin demanded a higher mechanical strength and was cross-linked with genipin (GB), resulting in a loss of chitosan active sites and consequently

a decrease in antimicrobial response, which was replaced by the addi-tion of silver nanoparticles The treatment of internal wounds is also possible with chitosan nanocomposites The work of Sundaram et al (2019) has exploited the use of an injectable nanocomposite containing

chitosan and nanobioglass Their work, tested in vivo, provides a fast a

secure blood clotting achieved by a synergistic effect between chitosan and nanoglass when in contact with blood

Biosensors are defined as chemical sensors capable to recognize the properties of biological components, and chitosan derivatives are ideal candidates for several biosensing applications ( Wang et al., 2016 )

Erdem et al (2014) tried to attach DNA aptamer immobilized graphene- oxide nanostructures to chitosan In this case, chitosan is attached to a pencil graphite electrode (PGE) surface The biosensor was developed and tested for the selective and sensitive detection of lysozyme (LYS), where low quantities could be a marker for some health problems Novel kinds of cancer and other diseases treatment are possible with the use of chitosan nanocomposites, particularly by the means of drug delivery Kankala et al (2020) successfully fabricated a versatile drug delivery platform by coating platinum (Pt) nanoparticles embedded chitosan polymer composite layer, over Zn-doped siliceous frameworks loaded with doxorubicin, a drug used to combat multidrug resistance (MDR) in cancer treatment This chitosan nanoderivative substantially facilitated deep tissue penetration efficacy due to the Pt nanometric sizes Also, the Pt nanoparticles synergistically participated in the

in-crease of the inhibition effect of the chemotherapeutic agent The in vivo

findings suggested that the innovative organic-inorganic nanohybrid material loaded with combinatorial therapeutics could be an alternative approach over conventional clinical strategies against cancer

4.4 Corrosion inhibition

Chitosan is a suitable polysaccharide for application as an effective corrosion inhibitor for many metallic substrates ( Qasim et al., 2019 ;

Umoren & Eduok, 2016 ) Chitosan shows a strong capability of adhesion

to a metal surface allow this polymer to be coated on metals to provide a protective barrier Chitosan's anti-corrosion ability is derived from its own molecular structure The chitosan molecule bears electron donate rich hydroxyl and amino groups capable of metal surface bonding, and

subsequent corrosion inhibition via coordinate bonding, as these

elec-trons are donated to the empty or partially occupied metallic orbitals

Electrospinning

3D printing

Melt molding

andNaCl leaching

Gas foaming CO2

Freeze-drying and Particulate leaching

Freeze-drying

Liquid hardening

Pore size (µm)

Fig 8 Schematic diagram of different shaping techniques using porous

chi-tosan materials as scaffolds for tissue engineering as a function of porosity and

pore size

( Umoren & Eduok, 2016 ) The easiness of chemical functionalization of

chitosan with nanospecies is a specific characteristic that can provide an

improvement on mechanical properties, adhesiveness, and barrier

ef-fect, which enhances the capability for corrosion protection ( Ashassi-

Sorkhabi & Kazempour, 2020 )

Chitosan materials have been applied mostly on steel (

Ashassi-Sor-khabi & Kazempour, 2020 ; Wei et al., 2020 ), magnesium ( Li et al.,

2018 ), titanium, aluminum ( Bouali et al., 2020 ), copper ( Jmiai et al.,

2017 ), and alloys for improving anti-corrosion and biodegradability

properties, as well as for providing higher biocompatibility Table 4

presents some works on the use of chitosan nanocomposites for anti-

corrosion purposes

Besides, other works have shown properties that enabled anti-fouling

and anti-corrosion properties simultaneously in metallic substrates

( Idumah et al., 2020 ) Noble metallic nanocomposites employing

chi-tosan as matrix material have been studied for mild steel coating

pro-tection even in chilled water circuits or in aggressive chloride media

with promising results ( Fetouh et al., 2020 ; Srivastava et al., 2019 )

Smart coatings were also obtained by chitosan, which can also be

applied in the production of sensors ( Carneiro et al., 2015 ; Zouaoui

et al., 2020 )

4.5 Other applications

Besides the above-mentioned applications, research on chitosan

nanocomposites has been developed for food packaging as active anti-microbial polymer or a biocidal nanocomposite ( Kaur et al., 2020 ;

Priyadarshi & Rhim, 2020 ; Virgili et al., 2021 ), energy storage ( Hassan

et al., 2014 ) for fuel cell application, a catalyst for some specific chemical and electrochemical reactions ( Nasri et al., 2020 ), and DNA extraction or separation ( G´omez P´erez et al., 2020 ) In those cases, different nanomaterials/chitosan combinations have been employed The low cost and versatility of chitosan, as well as the broad chemical and biochemical features, can be turned into future industrial products

5 Concluding remarks and future perspectives

In the present review, nanocomposites having chitosan as a matrix were presented and discussed regarding their chemical structure, shaping processes, properties, and applications There is a remarkable increase of studies about binding or embedding nanostructures into a chitosan matrix The nanoadditives presented here are mostly used to provide better mechanical, thermal, and chemical features among other desired properties, such as antimicrobial activity or drug delivery The surface structure of chitosan also provides a possibility of nanoparticle nucleation, and stabilization of noble metals due to electron donation of the amino reactant group Self-assembled chitosan binding capability, such as the layer-by-layer approach, also provides an adequate way to assure dispersion of ionic nanostructures

Due to some shapes or coatings required for specific applications, sophisticated processing methods have been increasingly developed Electrospinning and 3D printing, for example, start to become very popular in the production of chitosan nanocomposites instead of tradi-tional methods like solvent casting

The present review exposes some lack of research that might be further developed in the literature, such as the development of 3D printable chitosan nanocomposites for FDM, the use of chitosan as a nanofiber matrix for instance in wastewater treatment, and the feasi-bility of adapting techniques like injection molding and thermoforming for chitosan nanocomposites The combination of nanotechnology with innovative shaping and surface deposition techniques broadens the horizon of chitosan applications, such as biomedical, food packaging, energy storage, and wastewater treatment

Acknowledgments

The authors are grateful to the Coordenaç˜ao de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil, grant number 01) and Con-selho Nacional de Desenvolvimento Científico e Tecnol´ogico (CNPq, Brazil) for financial support (grant numbers: 06316/2007-2 and 311270/2017-4)

References

Abbasian, M., Massoumi, B., Mohammad-rezaei, R., Samadian, H., & Jaymand, M (2019) Scaffolding polymeric biomaterials: Are naturally occurring biological

macromolecules more appropriate for tissue engineering? International Journal of Biological Macromolecules, 134, 673–694 https://doi.org/10.1016/j

ijbiomac.2019.04.197

Abdelbasir, S M., El-Shewaikh, A M., El-Sheikh, S M., & Ali, O I (2021) Novel modified chitosan nanocomposites for Co(II) ions removal from industrial

wastewater Journal of Water Process Engineering, 41 https://doi.org/10.1016/j jwpe.2021.102008

Abinaya, B., Prasith, T P., & Ashwin, B (2019) Chitosan in surface modification for

bone tissue engineering applications Advanced Science News, 14(1900171), 1–10

https://doi.org/10.1002/biot.201900171

Ahmed, J., Mulla, M., & Maniruzzaman, M (2020) Rheological and dielectric behavior

of 3D-printable chitosan/graphene oxide hydrogels ACS Biomaterials Science & Engineering, 6(1), 88–99 https://doi.org/10.1021/acsbiomaterials.9b00201

Alaei, M., Atapour, M., & Labbaf, S (2020) Electrophoretic deposition of chitosan- bioactive glass nanocomposite coatings on AZ91 Mg alloy for biomedical

applications In Progress in organic coatings https://doi.org/10.1016/j

porgcoat.2020.105803

Alimard, P (2019) Fabrication and kinetic study of Nd-Ce doped Fe3O4-chitosan

nanocomposite as catalyst in Fenton dye degradation Polyhedron, 171, 98–107

https://doi.org/10.1016/j.poly.2019.06.058

Table 4

Examples of nanomaterials and deposition methods on metallic substrates in

systems containing chitosan as a matrix

Metal

substrates Nanoparticles applied Deposition method References

1020

Carbon

steel

Mg, Hydroxyapatite Spin coating (Sutha et al., 2015)

1020

Carbon

steel

deposition (2021Oliveira et al., )

1020

Carbon

steel

deposition (2020Oliveira et al., )

Ag Ag Electrodeposition (Pan et al., 2020)

AZ91 Mg

alloy Bioactive glass Electrophoretic deposition (Alaei et al., 2020)

C3003

aluminun

alloy

evaporation (Lai et al., 2021)

Cu SiO2 Layer-by-layer (Bahari et al., 2020)

Mg Cerium oxide Electrodeposition (Jia, Xiong, et al.,

2016)

Mg Graphene oxide Layer-by-layer (Gao et al., 2019)

Mg Graphene oxide,

Heparin Layer-by-layer (Gao et al., 2020)

et al., 2021) Mild steel TiO2 Dip coating (John et al., 2019)

Ti Au Electrodeposition (Farghali et al.,

2015)

Ti Graphene oxide Electrophoretic

deposition (Shi et al., 2016)

Ti Halloysite Electrophoretic

deposition (Molaei et al., 2016)

Ti Hydroxyapatite,

Halloysite Electrophoretic deposition (Yousefpour, 2018Molaei & )

Ti Mg, Sr, Halloysite Electrodeposition (Chozhanathmisra

et al., 2018) Ti-13Nb-

13Zr alloy Hydroxyapatite, Bioactive glass,

Fe3O4

Electrophoretic deposition (Singh et al., 2021) Ti-6Al-4V Bioactive glass Electrophoretic

deposition (2019Mahlooji et al., )

Ti6Al7Nb Ag, Au Solvent

evaporation (Kleszcz et al., 2021)

Al-Sherbini, A.-S A., Ghannam, H E A., El-Ghanam, G M A., El-Ella, A A., &

Youssef, A M (2019) Utilization of chitosan/Ag bionanocomposites as eco-friendly

photocatalytic reactor for bactericidal effect and heavy metals removal Heliyon, 5

(6), Article e01980 https://doi.org/10.1016/j.heliyon.2019.e01980

Amouzgar, P., Chan, E S., & Salamatinia, B (2017) Effects of ultrasound on

development of Cs/NAC nano composite beads through extrusion dripping for

acetaminophen removal from aqueous solution Journal of Cleaner Production, 165,

537–551 https://doi.org/10.1016/j.jclepro.2017.07.148

Anush, S., Chandan, H R., Gayathri, B., Asma, M N., Vishalaksi, B., & Kalluraya, B

(2020) Graphene oxide functionalized chitosan-magnetite nanocomposite for

removal of cu(II) and Cr(VI) from waste water International Journal of Biological

Macromolecules, 164, 4391–4402 https://doi.org/10.1016/j.ijbiomac.2020.09.059

Araldi da Silva, B., de Sousa Cunha, R., Val´erio, A., De Noni Junior, A., Hotza, D., &

G´omez Gonz´alez, S Y (2021) Electrospinning of cellulose using ionic liquids: An

overview on processing and applications European Polymer Journal, 147 https://doi

org/10.1016/j.eurpolymj.2021.110283

Asgari, E., Sheikhmohammadi, A., & Yeganeh, J (2020) Application of the Fe3O4-

chitosan nano-adsorbent for the adsorption of metronidazole from wastewater:

Optimization, kinetic, thermodynamic and equilibrium studies International Journal

of Biological Macromolecules, 164, 694–706 https://doi.org/10.1016/j

ijbiomac.2020.07.188

Ashassi-Sorkhabi, H., & Kazempour, A (2020) Chitosan, its derivatives and composites

with superior potentials for the corrosion protection of steel alloys: A comprehensive

review Carbohydrate Polymers, 237, Article 116110 https://doi.org/10.1016/j

carbpol.2020.116110

Azadmanesh, F., Pourmadadi, M., Zavar Reza, J., Yazdian, F., Omidi, M., &

Haghirosadat, B F (2021) Synthesis of a novel nanocomposite containing chitosan

as a three-dimensional printed wound dressing technique: Emphasis on gene

expression Biotechnology Progress, e3132, 1–13 https://doi.org/10.1002/btpr.3132

Aziz, S B., Abdullah, R M., Kadir, M F Z., & Ahmed, H M (2019) Non suitability of

silver ion conducting polymer electrolytes based on chitosan mediated by barium

titanate (BaTiO3) for electrochemical device applications Electrochimica Acta, 296,

494–507 https://doi.org/10.1016/j.electacta.2018.11.081

Aziz, S B., Brza, M A., Mohamed, P A., Kadir, M F Z., Hamsan, M H.,

Abdulwahid, R T., & Woo, H J (2019) Increase of metallic silver nanoparticles in

Chitosan:AgNt based polymer electrolytes incorporated with alumina filler Results in

Physics, 13(102326), 1–10 https://doi.org/10.1016/j.rinp.2019.102326

Aziz, S B., Karim, W O., & Ghareeb, H O (2020) The deficiency of chitosan:AgNO3

polymer electrolyte incorporated with titanium dioxide filler for device fabrication

and membrane separation technology Journal of Materials Research and Technology

https://doi.org/10.1016/j.jmrt.2020.02.097

Bahari, H S., Ye, F., Carrillo, E A T., Leliopoulos, C., Savaloni, H., & Dutta, J (2020)

Chitosan nanocomposite coatings with enhanced corrosion inhibition effects for

copper International Journal of Biological Macromolecules, 162, 1566–1577 https://

doi.org/10.1016/j.ijbiomac.2020.08.035

Bakhshayesh, R A D., Asadi, N., Alihemmati, A., Nasrabadi, H T., Montaseri, A.,

Davaran, S., & Abedelahi, A (2019) An overview of advanced biocompatible and

biomimetic materials for creation of replacement structures in the musculoskeletal

systems: Focusing on cartilage tissue engineering Journal of Biological Engineering, 9

https://doi.org/10.1186/s13036-019-0209-9

Bakhsheshi-rad, H R., Hamzah, E., Ying, W S., Razzaghi, M., Sharif, S., Ismail, A F., &

Berto, F (2021) Improved bacteriostatic and anticorrosion effects of

polycaprolactone/chitosan coated magnesium via incorporation of zinc oxide

Materials, 14, 1930–1945 https://doi.org/10.3390/ma14081930

Bakshi, P S., Selvakumar, D., Kadirvelu, K., & Kumar, N S (2020) Chitosan as an

environment friendly biomaterial – A review on recent modifications and

applications International Journal of Biological Macromolecules, 150, 1072–1083

https://doi.org/10.1016/j.ijbiomac.2019.10.113

Barra, A., Alves, Z., Ferreira, N M., Martins, M A., Oliveira, H., Ferreira, L P., &

Ferreira, P (2020) Biocompatible chitosan-based composites with properties

suitable for hyperthermia therapy Journal of Materials Chemistry B, 8(6), 1256–1265

https://doi.org/10.1039/c9tb02067e

Bouali, A C., Serdechnova, M., Blawert, C., Tedim, J., Ferreira, M G S., &

Zheludkevich, M L (2020) Layered double hydroxides (LDHs) as functional

materials for the corrosion protection of aluminum alloys: A review Applied

Materials Today, 21, Article 100857 https://doi.org/10.1016/j.apmt.2020.100857

Bozuyuk, U., Yasa, O., Yasa, I C., Ceylan, H., Kizilel, S., & Sitti, M (2018) Light-

triggered drug release from 3D-printed magnetic chitosan microswimmers ACS

Nano, 12(9), 9617–9625 https://doi.org/10.1021/acsnano.8b05997

Bulanov, E., Silina, N., Lelet, M., Knyazev, A., Smirnova, L., Aleynik, D., & Charykova, I

(2020) Study of physicochemical properties of nanohydroxyapatite–chitosan

composites Bulletin of Materials Science, 43(1), 1–6 https://doi.org/10.1007/

s12034-020-2065-0

Cai, N., Li, C., Han, C., Luo, X., Shen, L., Xue, Y., & Yu, F (2016) Tailoring mechanical

and antibacterial properties of chitosan/gelatin nanofiber membranes with Fe3O4

nanoparticles for potential wound dressing application Applied Surface Science, 369,

492–500 https://doi.org/10.1016/j.apsusc.2016.02.053

Carneiro, J., Tedim, J., & Ferreira, M G S (2015) Chitosan as a smart coating for

corrosion protection of aluminum alloy 2024: A review Progress in Organic Coatings,

89, 348–356 https://doi.org/10.1016/j.porgcoat.2015.03.008

Cebe, T., Ahuja, N., Monte, F., Awad, K., Vyavhare, K., Aswath, P., & Varanasi, V (2020)

Novel 3D-printed methacrylated chitosan-laponite nanosilicate composite scaffolds

enhance cell growth and biomineral formation in MC3T3 pre-osteoblasts Journal of

Materials Research, 35(1), 58–75 https://doi.org/10.1557/jmr.2018.260

Celebi, H., & Kurt, A (2015) Effects of processing on the properties of chitosan/cellulose

nanocrystal films Carbohydrate Polymers, 133, 284–293 https://doi.org/10.1016/j carbpol.2015.07.007

Chahal, S., Kumar, A., Shahitha, F., & Hussian, J (2019) Development of biomimetic electrospun polymeric biomaterials for bone tissue engineering A review

biomaterials for bone tissue engineering A review Journal of Biomaterials Science, Polymer Edition, 30(14), 1308–1355 https://doi.org/10.1080/

09205063.2019.1630699

Chatrabhuti, S., & Chirachanchai, S (2013) Single step coupling for multi-responsive

water-based chitin/chitosan magnetic nanoparticles Carbohydrate Polymers, 97(2),

441–450 https://doi.org/10.1016/j.carbpol.2013.04.076

Cheraghipour, E., & Pakshir, M (2020) Process optimization and modeling of Pb(II) ions adsorption on chitosan-conjugated magnetite nano-biocomposite using response

surface methodology Chemosphere, 260, Article 127560 https://doi.org/10.1016/j chemosphere.2020.127560

Chimisso, V., Maffeis, V., Hürlimann, D., Palivan, C G., & Meier, W (2020) Self- assembled polymeric membranes and nanoassemblies on surfaces: Preparation,

characterization, and current applications Macromolecular Bioscience, 20(1), 1–19

https://doi.org/10.1002/mabi.201900257

Chng, E J., Watson, A B., Suresh, V., Fujiwara, T., Bumgardner, J D., &

Gopalakrishnan, R (2019) Adhesion of electrosprayed chitosan coatings using

silane surface chemistry Thin Solid Films, 692(April), Article 137454 https://doi org/10.1016/j.tsf.2019.137454

Choo, C K., Kong, X Y., Goh, T L., Ngoh, G C., Horri, B A., & Salamatinia, B (2016) Chitosan/halloysite beads fabricated by ultrasonic-assisted extrusion-dripping and a

case study application for copper ion removal Carbohydrate Polymers, 138, 16–26

https://doi.org/10.1016/j.carbpol.2015.11.060

Chozhanathmisra, M., Govindaraj, D., Karthikeyan, P., Pandian, K., Mitu, L., & Rajavel, R (2018) Fabrication of bilayer coating of poly(3,4-

ethylenedioxythiophene)-Halloysite/Chitosan and Mg2+/Sr2+-doped HAP on titanium alloy for biomedical implant applications: Physicochemical and in vitro

biological performances studies Journal of Chemistry, 2018 https://doi.org/ 10.1155/2018/9813827

Crini, G., Morin-Crini, N., Fatin-Rouge, N., D´eon, S., & Fievet, P (2017) Metal removal

from aqueous media by polymer-assisted ultrafiltration with chitosan Arabian Journal of Chemistry, 10, S3826–S3839 https://doi.org/10.1016/j

arabjc.2014.05.020

da Silva, J C S., França, D B., Rodrigues, F., Oliveira, D M., Trigueiro, P., Silva Filho, E C., & Fonseca, M G (2021) What happens when chitosan meets bentonite under microwave-assisted conditions? Clay-based hybrid nanocomposites for dye

adsorption Colloids and Surfaces A: Physicochemical and Engineering Aspects, 609

https://doi.org/10.1016/j.colsurfa.2020.125584

Dakroury, G A., Abo-Zahra, S F., Hassan, H S., & Fathy, N A (2020) Utilization of silica–chitosan nanocomposite for removal of152+154Eu radionuclide from aqueous

solutions Journal of Radioanalytical and Nuclear Chemistry, 323(1), 439–455 https:// doi.org/10.1007/s10967-019-06951-6

De Mesquita, J P., Donnici, C L., & Pereira, F V (2010) Biobased nanocomposites from

layer-by-layer assembly of cellulose nanowhiskers with chitosan Biomacromolecules, 11(2), 473–480 https://doi.org/10.1021/bm9011985

Ding, L., Shan, X., Zhao, X., Zha, H., Chen, X., Wang, J., & Yu, G (2017) Spongy bilayer dressing composed of chitosan–Ag nanoparticles and chitosan–Bletilla striata

polysaccharide for wound healing applications Carbohydrate Polymers, 157,

1538–1547 https://doi.org/10.1016/j.carbpol.2016.11.040

Elviri, L., Foresti, R., Bergonzi, C., Zimetti, F., Marchi, C., Bianchera, A., & Bettini, R (2017) Highly defined 3D printed chitosan scaffolds featuring improved cell growth

Biomedical Materials (Bristol), 12(4), 1–12 https://doi.org/10.1088/1748-605X/ aa7692

Erathodiyil, N., & Ying, J Y (2011) Functionalization of inorganic nanoparticles for

bioimaging applications Accounts of Chemical Research, 44(10), 925–935 https:// doi.org/10.1021/ar2000327

Erdem, A., Eksin, E., & Muti, M (2014) Chitosan-graphene oxide based aptasensor for

the impedimetric detection of lysozyme Colloids and Surfaces B: Biointerfaces, 115,

205–211 https://doi.org/10.1016/j.colsurfb.2013.11.037

Esmaeili, M., Rajabi, L., & Bakhtiari, O (2019) Preparation and characterization of chitosan-boehmite nanocomposite membranes for pervaporative ethanol

dehydration Journal of Macromolecular Science, Part A: Pure and Applied Chemistry, 56(11), 1022–1034 https://doi.org/10.1080/10601325.2019.1646611

Farghali, R A., Fekry, A M., Ahmed, R A., & Elhakim, H K A (2015) Corrosion resistance of Ti modified by chitosan–gold nanoparticles for orthopedic

implantation International Journal of Biological Macromolecules, 79, 787–799

https://doi.org/10.1016/j.ijbiomac.2015.04.078

Fetouh, H A., Hefnawy, A., Attia, A M., & Ali, E (2020) Facile and low-cost green synthesis of eco-friendly chitosan-silver nanocomposite as novel and promising

corrosion inhibitor for mild steel in chilled water circuits Journal of Molecular Liquids, 319 https://doi.org/10.1016/j.molliq.2020.114355

Gang, F., Yan, H., Ma, C., Jiang, L., Gu, Y., Liu, Z., & Sun, X (2019) Robust magnetic double-network hydrogels with self-healing, MR imaging, cytocompatibility and 3D

printability Chemical Communications, 55(66), 9801–9804 https://doi.org/ 10.1039/c9cc04241e

Gao, F., Hu, Y., Gong, Z., Liu, T., Gong, T., Liu, S., & Pan, C (2019) Fabrication of chitosan/heparinized graphene oxide multilayer coating to improve corrosion

resistance and biocompatibility of magnesium alloys Materials Science and Engineering C, 104 https://doi.org/10.1016/j.msec.2019.109947

Gao, F., Hu, Y., Li, G., Liu, S., Quan, L., Yang, Z., & Pan, C (2020) Layer-by-layer deposition of bioactive layers on magnesium alloy stent materials to improve