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Citation: Kumar, A.; Yadav, S.;
Pramanik, J.; Sivamaruthi, B.S.;
Jayeoye, T.J.; Prajapati, B.G.;
Chaiyasut, C. Chitosan-Based
Composites: Development and
Perspective in Food Preservation and
Biomedical Applications. Polymers
2023,15, 3150. https://doi.org/
10.3390/polym15153150
Academic Editors: Chibuike C.
Udenigwe and Ogadimma
Desmond Okagu
Received: 5 July 2023
Revised: 17 July 2023
Accepted: 18 July 2023
Published: 25 July 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
polymers
Review
Chitosan-Based Composites: Development and Perspective in
Food Preservation and Biomedical Applications
Akash Kumar 1,2 , Sangeeta Yadav 3, Jhilam Pramanik 4, Bhagavathi Sundaram Sivamaruthi 5,6 ,
Titilope John Jayeoye 7, Bhupendra G. Prajapati 8,* and Chaiyavat Chaiyasut 6, *
1Department of Food Technology, SRM University, Sonipat 131029, India
2MM Institute of Hotel Management, Maharishi Markandeshwar (Deemed to be University),
Mullana 133207, India
3Department of Food Technology, Guru Jambheshwar University of Science and Technology,
Hisar 125001, India
4Department of Food Technology, William Carey University, Shillong 793019, India
5Office of Research Administration, Chiang Mai University, Chiang Mai 50200, Thailand;
sivamaruthi.b@cmu.ac.th
6Innovation Center for Holistic Health, Nutraceuticals, and Cosmeceuticals, Faculty of Pharmacy,
Chiang Mai University, Chiang Mai 50200, Thailand
7Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
8Shree S. K. Patel College of Pharmaceutical Education and Research, Ganpat University,
Mehsana 384012, India
*Correspondence: bhupen27@gmail.com (B.G.P.); chaiyavat@gmail.com (C.C.)
Abstract:
Chitin, which may be the second-most common polymer after cellulose, is the raw material
of chitosan. Chitosan has been infused with various plant extracts and subsidiary polymers to
improve its biological and physiological properties. Chitosan’s physicochemical properties are
enhanced by blending, making them potential candidates that can be utilized in multifunctional areas,
including food processing, nutraceuticals, food quality monitoring, food packaging, and storage.
Chitosan-based biomaterials are biocompatible, biodegradable, low toxic, mucoadhesive, and regulate
chemical release. Therefore, they are used in the biomedical field. The present manuscript highlights
the application of chitosan-based composites in the food and biomedical industries.
Keywords: fabrication; chitosan; nanocomposites; antimicrobial; polysaccharide
1. Introduction
Chitin is made by joining N-acetyl glucosamine residues through
β
(1–4) glycosidic
linkages and is the second-most prevalent natural polysaccharide after cellulose [
1
,
2
].
Chitin (Figure 1) is a naturally occurring structured crystalline microfibril in arthropods’
exoskeletons, fungi, and yeast cell walls. The main commercial sources of
α
-chitin are
crabs and prawn shells [
3
]. Squid comprises the
β
-form chitin, which is highly sensitive to
deacetylation and has stronger reactivity and solubility, as well as more affinity to solvents
and better swelling capacity than
α
-chitin [
4
]. The
γ
-form of chitin is generally found in
fungi and yeast [5].
N-acetylglucosamine and glucosamine residues are copolymerized to form chitosan.
It can be produced by deacetylating chitin using strong alkalis, which hydrolyzes the
acetamide groups. Several chemical processes are involved in converting chitin into chitosan
(CH). Demineralization, deproteinization, and deacetylation are the main steps in extracting
chitosan (Figure 2).
Polymers 2023,15, 3150. https://doi.org/10.3390/polym15153150 https://www.mdpi.com/journal/polymers
Polymers 2023,15, 3150 2 of 22
Polymers 2023, 15, x FOR PEER REVIEW 2 of 22
Figure 1. The chemical structure of chitin (created using BioRender.com on 4 July 2023).
N-acetylglucosamine and glucosamine residues are copolymerized to form chitosan.
It can be produced by deacetylating chitin using strong alkalis, which hydrolyzes the ac-
etamide groups. Several chemical processes are involved in converting chitin into chitosan
(CH). Demineralization, deproteinization, and deacetylation are the main steps in extract-
ing chitosan (Figure 2).
Figure 2. The steps in the synthesis of chitosan.
Chitosan and its derivatives exhibit anti-hypoxic, adaptogenic, immunostimulant,
antiviral, antibacterial, radioprotective, and hemostatic properties. In addition, they are
nontoxic, biocompatible, and biodegradable [6,7]. Since chitosan sulfate possesses antico-
agulant properties, it could be used to produce drugs that have an anticoagulant effect
[8,9]. Further, sulfated chitosan acts as an antioxidant [10]. Chitosan enhances the amount
of insulin and is a potential way to manage diabetes [11,12]. Chitosan in immunotherapy
is recommended as a potential anticancer drug that inhibits the development of infections
and tumor cells while promoting humoral and cellular immunity [13,14]. Chitosan-based
materials are used to treat wounds and promote the growth of granulation tissue and
fibroblasts [15].
Chitosan products may create transparent films to enhance foods’ quality and shelf
life. They are extremely dense and have antibacterial properties due to active amino
groups [16,17]. Chitosan may be utilized to make edible films that minimize water loss
and delay ripening due to its ability to build a durable, flexible, and partially permeable
film. These qualities make chitosan unique from other edible coatings [18,19]. Apart from
the above-stated advantages, chitosan-based films have disadvantages, including poor
UV-light barrier features and mechanical aributes. Chitosan films’ hydrophilicity ren-
ders them incredibly vulnerable to moisture. Therefore, different kinds of natural sub-
stances, such as phenolic compounds, essential oils, plant extracts, or other biopolymers,
can be added to improve the mechanical, physical, and biological properties of chitosan-
based films [20]. CH-based materials are employed in various industries (Figure 3),
Figure 1. The chemical structure of chitin (created using BioRender.com on 4 July 2023).
Polymers 2023, 15, x FOR PEER REVIEW 2 of 22
Figure 1. The chemical structure of chitin (created using BioRender.com on 4 July 2023).
N-acetylglucosamine and glucosamine residues are copolymerized to form chitosan.
It can be produced by deacetylating chitin using strong alkalis, which hydrolyzes the ac-
etamide groups. Several chemical processes are involved in converting chitin into chitosan
(CH). Demineralization, deproteinization, and deacetylation are the main steps in extract-
ing chitosan (Figure 2).
Figure 2. The steps in the synthesis of chitosan.
Chitosan and its derivatives exhibit anti-hypoxic, adaptogenic, immunostimulant,
antiviral, antibacterial, radioprotective, and hemostatic properties. In addition, they are
nontoxic, biocompatible, and biodegradable [6,7]. Since chitosan sulfate possesses antico-
agulant properties, it could be used to produce drugs that have an anticoagulant eěect
[8,9]. Further, sulfated chitosan acts as an antioxidant [10]. Chitosan enhances the amount
of insulin and is a potential way to manage diabetes [11,12]. Chitosan in immunotherapy
is recommended as a potential anticancer drug that inhibits the development of infections
and tumor cells while promoting humoral and cellular immunity [13,14]. Chitosan-based
materials are used to treat wounds and promote the growth of granulation tissue and
ębroblasts [15].
Chitosan products may create transparent ęlms to enhance foods’ quality and shelf
life. They are extremely dense and have antibacterial properties due to active amino
groups [16,17]. Chitosan may be utilized to make edible ęlms that minimize water loss
and delay ripening due to its ability to build a durable, Ěexible, and partially permeable
ęlm. These qualities make chitosan unique from other edible coatings [18,19]. Apart from
the above-stated advantages, chitosan-based ęlms have disadvantages, including poor
UV-light barrier features and mechanical aĴributes. Chitosan ęlms’ hydrophilicity ren-
ders them incredibly vulnerable to moisture. Therefore, diěerent kinds of natural sub-
stances, such as phenolic compounds, essential oils, plant extracts, or other biopolymers,
can be added to improve the mechanical, physical, and biological properties of chitosan-
based ęlms [20]. CH-based materials are employed in various industries (Figure 3),
Figure 2. The steps in the synthesis of chitosan.
Chitosan and its derivatives exhibit anti-hypoxic, adaptogenic, immunostimulant,
antiviral, antibacterial, radioprotective, and hemostatic properties. In addition, they are
nontoxic, biocompatible, and biodegradable [
6
,
7
]. Since chitosan sulfate possesses an-
ticoagulant properties, it could be used to produce drugs that have an anticoagulant
effect [
8
,
9
]. Further, sulfated chitosan acts as an antioxidant [
10
]. Chitosan enhances
the amount of insulin and is a potential way to manage diabetes [
11
,
12
]. Chitosan in
immunotherapy is recommended as a potential anticancer drug that inhibits the develop-
ment of infections and tumor cells while promoting humoral and cellular immunity [
13
,
14
].
Chitosan-based materials are used to treat wounds and promote the growth of granulation
tissue and fibroblasts [15].
Chitosan products may create transparent films to enhance foods’ quality and shelf
life. They are extremely dense and have antibacterial properties due to active amino
groups [
16
,
17
]. Chitosan may be utilized to make edible films that minimize water loss
and delay ripening due to its ability to build a durable, flexible, and partially permeable
film. These qualities make chitosan unique from other edible coatings [
18
,
19
]. Apart from
the above-stated advantages, chitosan-based films have disadvantages, including poor
UV-light barrier features and mechanical attributes. Chitosan films’ hydrophilicity renders
them incredibly vulnerable to moisture. Therefore, different kinds of natural substances,
such as phenolic compounds, essential oils, plant extracts, or other biopolymers, can be
added to improve the mechanical, physical, and biological properties of chitosan-based
films [
20
]. CH-based materials are employed in various industries (Figure 3), including
food, medicine, agriculture, and cosmetics [
21
,
22
]. This article emphasizes various ap-
proaches for fabricating chitosan-based composite food packaging systems and discusses
the applications of chitosan-based materials in food preservation and biomedical science.
Polymers 2023,15, 3150 3 of 22
Polymers 2023, 15, x FOR PEER REVIEW 3 of 22
including food, medicine, agriculture, and cosmetics [21,22]. This article emphasizes var-
ious approaches for fabricating chitosan-based composite food packaging systems and
discusses the applications of chitosan-based materials in food preservation and biomedi-
cal science.
Figure 3. The application of chitosan in different sectors.
2. Fabrication Methods for Composite Films/Coatings
2.1. Solution Casting
This process is a commonly utilized method to produce chitosan coatings and films.
First, it is dissolved in a solution, then the mixture is evaporated [23]. The process is af-
fordable and easy, and the polymer structure is produced due to intermolecular electro-
static and hydrogen bonding [24]. However, the film becomes brile due to this intermo-
lecular entanglement. To enhance the mechanical characteristics of the films, several plas-
ticizers (such as sugars, sorbitol, and glycerol) are added [25]. It is quite challenging to use
this method on a commercial scale, and for this, there is still a need for further improve-
ment. There are various steps in the fabrication process: Chitosan is first dissolved in an
acid solution (pH less than 6.0), then it is blended, mixed, or crosslinked with other bi-
opolymers, fillers, and functional materials at a different proportion, then the mixture is
stirred to obtain a homogeneous viscous solution, then it is filtered, sonicated, or centri-
fuged to remove any air bubbles and insoluble particles. After this, the solution is cast or
poured onto the surface for drying. After complete drying, the film is peeled off. Films are
often created using the solution-casting process on a laboratory scale; however, further
study is required to determine if it would be feasible to utilize solution-casting at a large
scale [26,27]. The general method to fabricate the film from the solution casting method is
shown in Figure 4.
Figure 3. The application of chitosan in different sectors.
2. Fabrication Methods for Composite Films/Coatings
2.1. Solution Casting
This process is a commonly utilized method to produce chitosan coatings and films.
First, it is dissolved in a solution, then the mixture is evaporated [
23
]. The process is afford-
able and easy, and the polymer structure is produced due to intermolecular electrostatic
and hydrogen bonding [
24
]. However, the film becomes brittle due to this intermolecular
entanglement. To enhance the mechanical characteristics of the films, several plasticizers
(such as sugars, sorbitol, and glycerol) are added [
25
]. It is quite challenging to use this
method on a commercial scale, and for this, there is still a need for further improvement.
There are various steps in the fabrication process: Chitosan is first dissolved in an acid
solution (pH less than 6.0), then it is blended, mixed, or crosslinked with other biopolymers,
fillers, and functional materials at a different proportion, then the mixture is stirred to ob-
tain a homogeneous viscous solution, then it is filtered, sonicated, or centrifuged to remove
any air bubbles and insoluble particles. After this, the solution is cast or poured onto the
surface for drying. After complete drying, the film is peeled off. Films are often created
using the solution-casting process on a laboratory scale; however, further study is required
to determine if it would be feasible to utilize solution-casting at a large scale [
26
,
27
]. The
general method to fabricate the film from the solution casting method is shown in Figure 4.
Polymers 2023, 15, x FOR PEER REVIEW 3 of 22
including food, medicine, agriculture, and cosmetics [21,22]. This article emphasizes var-
ious approaches for fabricating chitosan-based composite food packaging systems and
discusses the applications of chitosan-based materials in food preservation and biomedi-
cal science.
Figure 3. The application of chitosan in different sectors.
2. Fabrication Methods for Composite Films/Coatings
2.1. Solution Casting
This process is a commonly utilized method to produce chitosan coatings and films.
First, it is dissolved in a solution, then the mixture is evaporated [23]. The process is af-
fordable and easy, and the polymer structure is produced due to intermolecular electro-
static and hydrogen bonding [24]. However, the film becomes brile due to this intermo-
lecular entanglement. To enhance the mechanical characteristics of the films, several plas-
ticizers (such as sugars, sorbitol, and glycerol) are added [25]. It is quite challenging to use
this method on a commercial scale, and for this, there is still a need for further improve-
ment. There are various steps in the fabrication process: Chitosan is first dissolved in an
acid solution (pH less than 6.0), then it is blended, mixed, or crosslinked with other bi-
opolymers, fillers, and functional materials at a different proportion, then the mixture is
stirred to obtain a homogeneous viscous solution, then it is filtered, sonicated, or centri-
fuged to remove any air bubbles and insoluble particles. After this, the solution is cast or
poured onto the surface for drying. After complete drying, the film is peeled off. Films are
often created using the solution-casting process on a laboratory scale; however, further
study is required to determine if it would be feasible to utilize solution-casting at a large
scale [26,27]. The general method to fabricate the film from the solution casting method is
shown in Figure 4.
Figure 4. The solution-casting method of film formation.
The cast films of the chitosan blend and fucose-rich exopolysaccharide showed excel-
lent characteristics such as biodegradability, antibacterial activity, and gas barrier [
28
]. As a
result, the film may be used as a packaging material that extends the shelf life of foods.
Polymers 2023,15, 3150 4 of 22
2.2. Layer-by-Layer Assembly
Due to its versatility and ability to integrate the functional features of various polymers,
layer-by-layer assembly has been widely studied in producing nanocomposite films for
effectively managing material properties and functionality. It is a technique for making
multi-layered films that do not require any complicated equipment. In layer-by-layer
assembly, surface modification primarily depends on the mutual attraction and deposition
of alternating polyelectrolytes [
29
,
30
]. Artificial polymers, polysaccharides, proteins, and
other biopolymers that carry net charge can be considered polyelectrolytes. Deposition can
be accomplished by spraying solutions onto the substrate or submerging them in different
polyelectrolyte solutions. Both approaches have the potential for scalability. Layer-by-layer
deposition may create active packaging films and coatings by incorporating the active
agents [
31
,
32
]. The general method to fabricate the coating on food materials through the
layer-by-layer method is shown in Figure 5. It has been claimed that the layer-by-layer
method, combined with other techniques, successfully preserves food quality and extends
shelf life [33].
Polymers 2023, 15, x FOR PEER REVIEW 4 of 22
Figure 4. The solution-casting method of film formation.
The cast films of the chitosan blend and fucose-rich exopolysaccharide showed excel-
lent characteristics such as biodegradability, antibacterial activity, and gas barrier [28]. As
a result, the film may be used as a packaging material that extends the shelf life of foods.
2.2. Layer-by-Layer Assembly
Due to its versatility and ability to integrate the functional features of various poly-
mers, layer-by-layer assembly has been widely studied in producing nanocomposite films
for effectively managing material properties and functionality. It is a technique for making
multi-layered films that do not require any complicated equipment. In layer-by-layer as-
sembly, surface modification primarily depends on the mutual araction and deposition
of alternating polyelectrolytes [29,30]. Artificial polymers, polysaccharides, proteins, and
other biopolymers that carry net charge can be considered polyelectrolytes. Deposition
can be accomplished by spraying solutions onto the substrate or submerging them in dif-
ferent polyelectrolyte solutions. Both approaches have the potential for scalability. Layer-
by-layer deposition may create active packaging films and coatings by incorporating the
active agents [31,32]. The general method to fabricate the coating on food materials
through the layer-by-layer method is shown in Figure 5. It has been claimed that the layer-
by-layer method, combined with other techniques, successfully preserves food quality
and extends shelf life [33].
Figure 5. Layer-by-layer method of coating foods.
2.3. Extrusion
Most commercial plastic packaging films are made via extrusion techniques. Due to
fast fabrication time and less energy-intensive nature, extrusion is frequently chosen over
solution casting techniques [34,35]. The extrusion process includes several steps, such as
preparing and mixing raw materials. Blending the mixture in an extruder for paleization,
cuing the extrudates into pellets via a pelletizer, then drying the pellets and extruding
them into the sheets via another extruder. Finally, film extruders blow the mixed resins
into a film (Figure 6).
Figure 5. Layer-by-layer method of coating foods.
2.3. Extrusion
Most commercial plastic packaging films are made via extrusion techniques. Due to
fast fabrication time and less energy-intensive nature, extrusion is frequently chosen over
solution casting techniques [
34
,
35
]. The extrusion process includes several steps, such as
preparing and mixing raw materials. Blending the mixture in an extruder for palettization,
cutting the extrudates into pellets via a pelletizer, then drying the pellets and extruding
them into the sheets via another extruder. Finally, film extruders blow the mixed resins into
a film (Figure 6).
Polymers 2023, 15, x FOR PEER REVIEW 4 of 22
Figure 4. The solution-casting method of film formation.
The cast films of the chitosan blend and fucose-rich exopolysaccharide showed excel-
lent characteristics such as biodegradability, antibacterial activity, and gas barrier [28]. As
a result, the film may be used as a packaging material that extends the shelf life of foods.
2.2. Layer-by-Layer Assembly
Due to its versatility and ability to integrate the functional features of various poly-
mers, layer-by-layer assembly has been widely studied in producing nanocomposite films
for effectively managing material properties and functionality. It is a technique for making
multi-layered films that do not require any complicated equipment. In layer-by-layer as-
sembly, surface modification primarily depends on the mutual araction and deposition
of alternating polyelectrolytes [29,30]. Artificial polymers, polysaccharides, proteins, and
other biopolymers that carry net charge can be considered polyelectrolytes. Deposition
can be accomplished by spraying solutions onto the substrate or submerging them in dif-
ferent polyelectrolyte solutions. Both approaches have the potential for scalability. Layer-
by-layer deposition may create active packaging films and coatings by incorporating the
active agents [31,32]. The general method to fabricate the coating on food materials
through the layer-by-layer method is shown in Figure 5. It has been claimed that the layer-
by-layer method, combined with other techniques, successfully preserves food quality
and extends shelf life [33].
Figure 5. Layer-by-layer method of coating foods.
2.3. Extrusion
Most commercial plastic packaging films are made via extrusion techniques. Due to
fast fabrication time and less energy-intensive nature, extrusion is frequently chosen over
solution casting techniques [34,35]. The extrusion process includes several steps, such as
preparing and mixing raw materials. Blending the mixture in an extruder for paleization,
cuing the extrudates into pellets via a pelletizer, then drying the pellets and extruding
them into the sheets via another extruder. Finally, film extruders blow the mixed resins
into a film (Figure 6).
Figure 6.
The extrusion method for the preparation of the film (adapted and recreated from Al-
sadi et al. [36]).
The films manufactured through extrusion have adequate mechanical and thermal
characteristics. It is a potential method for film manufacture, but more research must be
Polymers 2023,15, 3150 5 of 22
conducted to form chitosan-based films via this technique [
37
]. The extrusion method
produces an antimicrobial film from a mixture of chitosan, starch, and poly (lactic acid) to
preserve food with high water activity [38].
2.4. Coatings (Spraying, Dipping, or Spreading)
The coating can be applied to the skin to extend the shelf life of fresh items like fruits,
vegetables, fish, meat, etc. [
39
]. The most common methods of food coating are spraying,
dipping, or spreading (Figure 7). With a few instruments, such as a brush or spatula, spread
coating is accomplished. The coating is a useful method to prevent microbial growth,
enhance the shelf life, and maintain quality keeping [40].
Polymers 2023, 15, x FOR PEER REVIEW 5 of 22
Figure 6. The extrusion method for the preparation of the film (adapted and recreated from Alsadi
et al. [36]).
The films manufactured through extrusion have adequate mechanical and thermal
characteristics. It is a potential method for film manufacture, but more research must be
conducted to form chitosan-based films via this technique [37]. The extrusion method pro-
duces an antimicrobial film from a mixture of chitosan, starch, and poly (lactic acid) to
preserve food with high water activity [38].
2.4. Coatings (Spraying, Dipping, or Spreading)
The coating can be applied to the skin to extend the shelf life of fresh items like fruits,
vegetables, fish, meat, etc. [39]. The most common methods of food coating are spraying,
dipping, or spreading (Figure 7). With a few instruments, such as a brush or spatula,
spread coating is accomplished. The coating is a useful method to prevent microbial
growth, enhance the shelf life, and maintain quality keeping [40].
The coating procedure entails several steps:
1. Preparation of raw materials through mixing the right proportions of chitosan and
fillers.
2. Preparation of coating samples through various methods such as irradiating, heating,
mixing, and steam flash pasteurizing.
3. Sanitizing of the food samples through sodium hypochlorite.
4. Application of the chitosan-based composite solutions to food through the sterile
spreader.
5. Drying under specific circumstances.
6. Packaging and storage in suitable conditions [41].
Antimicrobial components may migrate from the films to the food to increase the
shelf life of food [42]. In an active packaging system, the coating is formed by dipping or
spraying methods. In dipping methods, food is dipped into a previously made acidic chi-
tosan solution that also contains preservatives and plasticizers to enhance the efficiency
of the coating or film [43]. The coating process typically involves dipping the food for a
short period in the composite solutions, draining the excess solution, and then drying the
samples. Food products have been coated with one or more layers using various dipping
techniques. However, double-dipping was preferred over three or more dipping in certain
circumstances. This method is easy and affordable because there is no need for compli-
cated equipment, and it gives high preservation efficiency. Similar procedures are fol-
lowed for spray coating, except spraying is conducted with a sprayer supported by com-
pressed air [44]. While dipping and spraying processes are easy, economical, and often
used in most food manufacturing lines, these methods can hinder the food’s sensory qual-
ities [45]. Therefore, it is strongly advised to employ this approach carefully to apply chi-
tosan-based biopolymer coatings or films. These methods are used for coating fruits and
vegetables to improve their shelf life [46].
Figure 7. The different methods of coating such as (a) spraying, (b) dipping, and (c) spreading.
The coating procedure entails several steps:
1 Preparation of raw materials through mixing the right proportions of chitosan and fillers.
2
Preparation of coating samples through various methods such as irradiating, heating,
mixing, and steam flash pasteurizing.
3 Sanitizing of the food samples through sodium hypochlorite.
4
Application of the chitosan-based composite solutions to food through the ster-
ile spreader.
5 Drying under specific circumstances.
6 Packaging and storage in suitable conditions [41].
Antimicrobial components may migrate from the films to the food to increase the
shelf life of food [
42
]. In an active packaging system, the coating is formed by dipping
or spraying methods. In dipping methods, food is dipped into a previously made acidic
chitosan solution that also contains preservatives and plasticizers to enhance the efficiency
of the coating or film [
43
]. The coating process typically involves dipping the food for a
short period in the composite solutions, draining the excess solution, and then drying the
samples. Food products have been coated with one or more layers using various dipping
techniques. However, double-dipping was preferred over three or more dipping in certain
circumstances. This method is easy and affordable because there is no need for complicated
equipment, and it gives high preservation efficiency. Similar procedures are followed for
spray coating, except spraying is conducted with a sprayer supported by compressed
air [
44
]. While dipping and spraying processes are easy, economical, and often used in
most food manufacturing lines, these methods can hinder the food’s sensory qualities [
45
].
Therefore, it is strongly advised to employ this approach carefully to apply chitosan-based
biopolymer coatings or films. These methods are used for coating fruits and vegetables to
improve their shelf life [46].
2.5. Crosslinking
Two polymers are linked together via a crosslink developed by a chemical process,
covalent or ionic bonds, or weaker bonding interactions [
47
] (Figure 8). The component
polymers in the crosslinked composite may exhibit new characteristics when combined
Polymers 2023,15, 3150 6 of 22
while retaining their unique characteristics. An interpenetrating polymer network (IPN) is
one sort of crosslink that has been extensively studied. Among other chemical substances,
cross-linkers include polymers [
48
], oxides [
49
], metals [
50
], and amino acids [
51
]. Various
polymers may successfully create an IPN with the chitin-based material, including polymers
made of epoxides, alcohols, and carboxylic acids. However, some of these polymers
may affect membrane development, making their usage undesirable [
52
]. Crosslinking
techniques can be used to manufacture food packaging films. The food packaging film was
developed using a mixture of chitosan and gelatin with genipin as a crosslinked filler and a
hybridization of quercetin and rosemary essential oil. The film has excellent UV protective,
antioxidant, and antibacterial properties. Thus, the developed film can be employed as
active food packaging materials [53].
Polymers 2023, 15, x FOR PEER REVIEW 6 of 22
Figure 7. The different methods of coating such as (a) spraying, (b) dipping, and (c) spreading.
2.5. Crosslinking
Two polymers are linked together via a crosslink developed by a chemical process,
covalent or ionic bonds, or weaker bonding interactions [47] (Figure 8). The component
polymers in the crosslinked composite may exhibit new characteristics when combined
while retaining their unique characteristics. An interpenetrating polymer network (IPN)
is one sort of crosslink that has been extensively studied. Among other chemical sub-
stances, cross-linkers include polymers [48], oxides [49], metals [50], and amino acids [51].
Various polymers may successfully create an IPN with the chitin-based material, includ-
ing polymers made of epoxides, alcohols, and carboxylic acids. However, some of these
polymers may affect membrane development, making their usage undesirable [52]. Cross-
linking techniques can be used to manufacture food packaging films. The food packaging
film was developed using a mixture of chitosan and gelatin with genipin as a crosslinked
filler and a hybridization of quercetin and rosemary essential oil. The film has excellent
UV protective, antioxidant, and antibacterial properties. Thus, the developed film can be
employed as active food packaging materials [53].
Figure 8. The schematic of the crosslinking for developing polymeric composite (created using Bio-
Render.com on 4 July 2023).
2.6. Electrospinning
A spinneret, a collector (a grounded wire), and a high-voltage power source comprise
a simple electrospinning system (Figure 9). Spinneret (which contains polymer solution)
has a blunt-tip needle and a syringe pump that regulates the flow of the polymer solution
[54]. To control the structure of electrospun nanofibers (coaxial setup for core-sheath and
hollow nanofibers [55]) or to increase the throughput of electrospun nanofibers (multi-
needle electrospinning setup [56]), numerous advanced electrospinning setups have been
developed [57]. Typically, the electrospinning procedure may be broken down into four
steps:
(1) Formation of the cone-shaped jet from a pendant droplet by charging it in an electric
field.
(2) Lengthening of the charged jet.
(3) Stretching and thinning of the charged jet under the electric field causes bending in-
stability.
(4) Solidification and collection of the jet as solid fibers on a grounded collector [54].
The development of chitosan-based fibers for wound healing will largely depend on
incorporating suitable copolymers. However, electrospinning still has technical difficul-
ties producing chitosan-based fibers [58].
Figure 8.
The schematic of the crosslinking for developing polymeric composite (created using
BioRender.com on 4 July 2023).
2.6. Electrospinning
A spinneret, a collector (a grounded wire), and a high-voltage power source comprise a
simple electrospinning system (Figure 9). Spinneret (which contains polymer solution) has
a blunt-tip needle and a syringe pump that regulates the flow of the polymer solution [
54
].
To control the structure of electrospun nanofibers (coaxial setup for core-sheath and hollow
nanofibers [
55
]) or to increase the throughput of electrospun nanofibers (multi-needle
electrospinning setup [
56
]), numerous advanced electrospinning setups have been devel-
oped [57]. Typically, the electrospinning procedure may be broken down into four steps:
(1)
Formation of the cone-shaped jet from a pendant droplet by charging it in an elec-
tric field.
(2)
Lengthening of the charged jet.
(3)
Stretching and thinning of the charged jet under the electric field causes bending
instability.
(4)
Solidification and collection of the jet as solid fibers on a grounded collector [54].
The development of chitosan-based fibers for wound healing will largely depend on
incorporating suitable copolymers. However, electrospinning still has technical difficulties
producing chitosan-based fibers [58].
This section summarizes the various fabrication methods used (such as solution-
casting, layer-by-layer, extrusion, coating, crosslinking, and electrospinning) to create
chitosan-based materials that may be used in the biomedical and food industries. Fabrica-
tion methods can be used to develop a chitosan-based composite to enhance the mechanical,
UV-shielding, antibacterial, and antioxidant properties. As a result, chitosan composites
are suggested as potential materials to be utilized in the biomedical and food sectors.
Polymers 2023,15, 3150 7 of 22
Polymers 2023, 15, x FOR PEER REVIEW 7 of 22
Figure 9. Schematic representation of the fundamental electrospinning arrangement.
This section summarizes the various fabrication methods used (such as solution-cast-
ing, layer-by-layer, extrusion, coating, crosslinking, and electrospinning) to create chi-
tosan-based materials that may be used in the biomedical and food industries. Fabrication
methods can be used to develop a chitosan-based composite to enhance the mechanical,
UV-shielding, antibacterial, and antioxidant properties. As a result, chitosan composites
are suggested as potential materials to be utilized in the biomedical and food sectors.
3. Improvisation of Chitosan-Based Composites
Films and coatings made from chitosan have a few drawbacks, such as poor water
resistance, reduced mechanical characteristics, and poor ultraviolet light barrier proper-
ties [20,59]. To overcome these problems, chitosan may be mixed with organic biopoly-
mers, including polysaccharides and proteins. The blend of chitosan and polysaccharide
blends often offers several benefits over other biopolymer blends, including the inexpen-
sive, stable, and enhanced characteristics of the generated films [47]. Chitosan may also
blend with polyphenols, plant extracts, polyvinyl alcohol, metal/metal oxide nanoparti-
cles, and clay [60].
Chitosan-based composite films have been studied for their physical, mechanical,
and biological characteristics. For example, a compact structure polymer composite was
made when corn starch was blended with chitosan. The composite films had improved
elongation, tensile strength, and other mechanical properties. They reduced water vapor
permeability, an important film characteristic for packaging used in the food sector [61].
The composite film of starch and chitosan blend has improved biological, mechani-
cal, and physical characteristics. The chitosan-starch films showed antibacterial action
against Listeria innocua, indicating that these composites might be utilized in the packag-
ing sector to guarantee the safety of food items [62]. Kaya et al. described a blend of spo-
ropollenin-chitosan and the study suggested that the higher amounts of sporopollenin in
chitosan-based films were beneficial in terms of improved physical, chemical, and me-
chanical characteristics, hydrophobicity, and biological properties [63].
Through the blending of pectin and chitosan, a biodegradable packaging material
was made that could be used for food packing. The composite film has a lower water va-
por transmission rate than the sole pectic film. Similarly, composite film has improved
tensile strength and transparency [64].
Phenolic chemicals exhibit synergistic effects and improve the antibacterial and anti-
oxidant activities of composite films when blended with chitosan [59]. The existence of
the crystalline phase, the type of chitosan matrix, the microstructure of the chitosan net-
work, and intramolecular bonding all have a significant role in the mechanical properties
of the film [65,66]. According to the literature, different polyphenols have different effects
on the mechanical properties of films; for example, the tensile strength (TS) and elongation
Figure 9. Schematic representation of the fundamental electrospinning arrangement.
3. Improvisation of Chitosan-Based Composites
Films and coatings made from chitosan have a few drawbacks, such as poor water
resistance, reduced mechanical characteristics, and poor ultraviolet light barrier proper-
ties [
20
,
59
]. To overcome these problems, chitosan may be mixed with organic biopolymers,
including polysaccharides and proteins. The blend of chitosan and polysaccharide blends
often offers several benefits over other biopolymer blends, including the inexpensive, sta-
ble, and enhanced characteristics of the generated films [
47
]. Chitosan may also blend
with polyphenols, plant extracts, polyvinyl alcohol, metal/metal oxide nanoparticles,
and clay [60].
Chitosan-based composite films have been studied for their physical, mechanical,
and biological characteristics. For example, a compact structure polymer composite was
made when corn starch was blended with chitosan. The composite films had improved
elongation, tensile strength, and other mechanical properties. They reduced water vapor
permeability, an important film characteristic for packaging used in the food sector [61].
The composite film of starch and chitosan blend has improved biological, mechanical,
and physical characteristics. The chitosan-starch films showed antibacterial action against
Listeria innocua, indicating that these composites might be utilized in the packaging sector
to guarantee the safety of food items [
62
]. Kaya et al. described a blend of sporopollenin-
chitosan and the study suggested that the higher amounts of sporopollenin in chitosan-
based films were beneficial in terms of improved physical, chemical, and mechanical
characteristics, hydrophobicity, and biological properties [63].
Through the blending of pectin and chitosan, a biodegradable packaging material was
made that could be used for food packing. The composite film has a lower water vapor
transmission rate than the sole pectic film. Similarly, composite film has improved tensile
strength and transparency [64].
Phenolic chemicals exhibit synergistic effects and improve the antibacterial and antiox-
idant activities of composite films when blended with chitosan [
59
]. The existence of the
crystalline phase, the type of chitosan matrix, the microstructure of the chitosan network,
and intramolecular bonding all have a significant role in the mechanical properties of the
film [
65
,
66
]. According to the literature, different polyphenols have different effects on the
mechanical properties of films; for example, the tensile strength (TS) and elongation at the
break (EAB) of the chitosan-propolis composite film are increased by the addition of propolis
extract [
67
]. The blending of gallic acid [
68
], epigallocatechin gallate nanocapsules [
69
], el-
lagic acid [
70
], protocatechuic acid [
71
], proanthocyanidins [
72
], syringic acid [
73
], phenolic
acids [
21
], or curcumin [
74
] into chitosan-based films increases the resulting composite’s
mechanical strength.
In chitosan-based composite films, blending of olive leaf extract [
75
] or purple rice
and black rice extracts [
76
] provides an improvement in TS and EAB; however, adding
Punica granatum peel extract [
77
], Thymus vulgaris extract [
78
], Curcuma longa extract [
79
],
Polymers 2023,15, 3150 8 of 22
Mangifera indica leaf extract [
80
], or purple-fleshed sweet potato extract [
81
] only improved
the TS; additionally, adding Punica granatum L. extract [
82
], Citrus paradisi seed extract [
83
],
Berberis crataegina fruit extract [
84
], and Nigella sativa seedcake extract [
85
] improved only
the elongation. In contrast, incorporating certain polyphenols may weaken the mechan-
ical strength of the composite film. For example, blending Chinese chive root extract in
chitosan reduces the tensile strength of the composite film [
65
]. Similarly, composite film
incorporated with apple peel polyphenols exhibited lower tensile strength than controlled
film [
66
]. Therefore, the blending of appropriate polyphenols plays an important role in
the mechanical characteristics of the composite film.
Blending propolis in the chitosan matrix reduced the water vapor and oxygen trans-
mission rates of the composite film [
86
]. The water vapor transmission rate was reduced
when polyphenol-rich natural extracts (Allium tuberosum root extract [
64
], pomegranate
peel extract [
82
], Nigella sativa seedcake extract [
85
], Lycium barbarum fruit extract [
87
],
Herba Lophatheri extract [
88
], and olive leaves extract [
75
]) were blended with chitosan. The
antioxidant efficacy of chitosan and phenolic compounds-based composite films is greater
than ordinary ones [21,71].
Ammonium chitosan/polyvinyl alcohol composite film has reduced water vapor
permeability with strong tensile strength [
89
]. The composite film of polyvinyl alcohol,
chitosan, and different D-Limonene (DL) concentrations exhibited good tensile strength
and low water vapor permeability. Additionally, the composite films exhibited antibacterial
activity against Staphylococcus aureus and Escherichia coli [
90
]. Yu et al. found that adding
silica to the polyvinyl alcohol/chitosan films might increase tensile strength by up to 45%
by creating hydrogen bonds between silica and polyvinyl alcohol or chitosan. The addition
of silica reduced the oxygen and moisture transmission rate and increased the shelf life by
three times [
91
]. A composite film of silver nanoparticles/gelatin/chitosan had antibacterial
capabilities against Staph. aureus and E. coli, as well as improved mechanical and water
barrier characteristics [
92
]. The incorporation of ginger essential oil in nanocomposite films
of chitosan and montmorillonite exhibited improved the film’s ability to block light, gases,
and water vapor [
93
]. In addition, incorporating graphene oxide into the chitosan film
improved the tensile strength and thermal properties [
94
]. The above-stated properties of
chitosan composite proved that these composites may be utilized in the food industry.
4. Application of Chitosan-Based Composite in the Food Industry
4.1. Utilization of Chitosan-Based Composite in the Preservation of Seafood
Chitosan has been shown to prolong the shelf life of fish and fishery products by
preventing the growth of spoiling bacteria and maintaining product quality [
95
]. During
the 20 days of storage of grass carp fillets, chitosan coating prevented microbial growth
and lipid degradation, decreased water loss, and maintained pH [
96
]. Additionally, it
was found that the total viable and psychrotrophic counts were inhibited, resulting in less
amine synthesis. Chitosan coating may reduce lipid oxidation by producing chelating-free
ions [
97
]. Active substances can be incorporated into chitosan-based films to improve
their ability for preservation [
98
]. A coating made of chitosan and curcumin nanoparticles
dramatically reduced the bacteria count and maintained it within the allowable range
in Schizothoraxpranati fillets. Chitosan and the curcumin-based film might squelch free
radicals and protein degradation in fillets and successfully delay lipid oxidation and the
production of volatile amines [
99
]. Red sea bream fillets were protected from oxidation,
amine development, and total viable count by a chitosan nanoparticle-based coating con-
taining cinnamon-perilla essential oil and anthocyanidins [
100
]. Red sea bream maintained
at 4
◦
C benefited from active packaging made of chitosan that included ginger essential
oil to prevent the growth of bacteria and lipid oxidation [
101
]. For 28 days of storage of
shrimps, the chances of lipid oxidation were decreased by a film made of chitosan and tea
polyphenols [
102
]. Additionally, the coatings made of chitosan postponed the shrimps’
proteolysis, an enzymatic process.
Polymers 2023,15, 3150 9 of 22
The shelf life of vacuum-packed rainbow trout was examined by Rezaeifar et al. [
103
]
concerning the impact of chitosan coatings with lemon verbena extract and essential oil.
The investigation showed that the treated samples had reduced the quantity of peroxide,
total volatile basic nitrogen, and H
2
S-producing bacteria. The application of essential oil
and extract of lemon verbena improved the fish’s sensory quality. Ehsani et al. studied
the impact of chitosan films combined with sage essential oil on the deterioration of fish
burgers made up of common carp flesh. According to the findings, coatings successfully
inhibit or retard the growth of harmful and spoilage-causing bacteria [
104
]. The sage
essential oil introduction prevents the production of off-flavor. Demircan et al. treated
mackerel fillet with chitosan comprising ethyl lauroyl arginate and lemon essential oil. The
results revealed that the samples treated with composite had more antioxidant capacity
than the untreated samples [
105
]. According to Zamani et al., chitosan and cumin extract
coating showed antibacterial and antioxidant characteristics and preserved the quality of
rainbow trout fillets [106].
4.2. Utilization of Chitosan-Based Composite in the Preservation of Meat and Meat Products
Meats are perishable and more susceptible to pollutants that can enter the interior
layers of muscle [
107
]. Once microbes have penetrated the inner layers, it is difficult to kill
them by cooking [
108
]. Food oxidation and microbial spoilage are two significant issues
that impact meat’s quality and shelf life. Packing materials are increasingly made with
antimicrobials and antioxidants instead of artificial food preservatives.
Numerous studies have been conducted to find natural active compounds that can
replace artificial antioxidants and antimicrobials because these are associated with potential
health risks. Therefore, numerous studies have been conducted on producing chitosan-
based films and utilizing them in processing meat products, including red meat, poultry,
and pork [
109
]. Green tea extract has been included in a chitosan-based film as an active
material to extend the shelf life of pork sausages [
110
]. The findings revealed that pork
sausages wrapped in chitosan film containing green tea extract exhibited fewer changes
in color, texture, 2-thiobarbituric acid value, sensory qualities, and microbial growth than
the control. Finally, they proposed that adding green tea extract to chitosan film might
improve its antioxidant and antibacterial qualities, preserve the quality, and extend the
shelf life of pork sausages. In another research, a chitosan-based film was synthesized that
included acetic acid. The impact of this film on the shelf life of meat was investigated.
Results revealed that chitosan-acetic acid film could retain the freshness and quality of
chilled meat for longer periods than low-density polyethylene (LDPE) film. The chitosan
films successfully suppressed the microbial growth in chilled meat during storage. The
findings showed that the antibacterial properties of the chitosan films on meat were mostly
responsible for controlling microbial growth suppression [111].
Coating made from chitosan, pomegranate peel extract, and thymus essential oil
increased the shelf life of fresh beef [
112
]. The findings of this study demonstrated that
the coating successfully reduced bacterial numbers and the chance of lipid oxidation.
Zhang et al. developed a coating made of chitosan, gelatin, and tarragon essential oil to
increase the shelf life of pork slices stored in the refrigerator. The outcomes demonstrated
that the coatings maintain the quality of the pork slices. When the skinned turkey breast
fillet was coated with chitosan coatings consisting of oregano essential oil and grape seed
extract, there was a fall in Enterobacteriaceae counts. The study also revealed that these
coatings might lessen lipid oxidation [
113
]. Gaba et al. studied the effectiveness of chitosan
films combined with oregano and thyme essential oils towards meat deterioration and
harmful microorganisms. The manufactured films inhibited the psychrophilic bacteria’s
ability to proliferate [114].
4.3. Utilization of Chitosan-Based Composite in the Preservation of Postharvest Foods
Most horticultural commodities have a relatively limited postharvest life, which means
fresh agricultural produce is perishable. Even after harvest, fruits and vegetables continue
Polymers 2023,15, 3150 10 of 22
to breathe and perspire, reducing their shelf life and degrading their freshness. Fruits
change physiologically and biochemically during ripening, including the degradation of
chlorophyll, the breakdown of cell walls by enzymes, changes in sugar content, changes in
respiratory activity, the formation of ethylene, and variations in the amounts of aromatic
compounds [
115
]. Reactive oxygen species can injure cells and degrade the quality of
fruits and vegetables when released in excess or generated during electron transport in the
mitochondria [
116
]. Many scientists have researched organic, nontoxic compounds that
may be utilized to prolong the shelf-life of fruits and vegetables after harvest. In one of
these studies, strawberry fruit was coated with an edible chitosan-based coating containing
Thymus capitatus essential oil, which increased the fruit’s shelf life in cold storage by up to
15 days [117].
Biopolymer-based edible film wrapping or coating is cheap, easy, and efficient in
preventing moisture loss and lowering the degradation and respiration pace. It has been
discovered that chitosan-based composites combined with nanomaterials and natural an-
timicrobials are beneficial for extending shelf life and preserving the quality of postharvest
products [118]. The inclusion of nano-fillers improves the physicochemical and biological
characteristics of natural biopolymers. Fresh fruits and vegetables with chitosan-based
coating showed less weight loss, firmer texture, more antioxidant activity, and soluble
solids than the control [
119
]. Quaternized chitosan films with carboxymethyl cellulose
increase the shelf life of whole bananas [120].
A study finds the impact of chitosan composite film with apple peel polyphenol on the
shelf life of strawberries [
121
]. Compared to uncoated fruits, the coated fruits’ antioxidant
levels remained merely steady. As a result, decreased antioxidant capacity during storage
deteriorates the quality of fresh produce. Effective oxygen radical scavengers are directly
connected to the capacity of chitosan-based apple peel polyphenol composite covering to
prevent decay, decrease enzymatic activity, and maintain the high-quality characteristics of
fruits, leading to the degradation of antioxidant chemicals [
122
]. Yage et al. method of in-
ducing film formation on mangoes’ surfaces by covering them with chitosan/nano-titanium
dioxide decreased deterioration and water loss while delaying respiratory peaks [
123
]. Red
grapes’ freshness was investigated using a biodegradable, antibacterial chitosan starch
composite film [
124
]. According to the findings, the biodegradable film might be used to
preserve grapes because of its superior water retention and antibacterial effectiveness. In
similar studies, Yang et al. utilized chitosan coating consisting of blueberry leaf extract to
preserve the postharvest quality of fresh blueberries [
125
]. The composite film made from
chitosan and plant extracts was rich in antioxidants [
126
]. The creation of a composite film
made of chitosan and banana peel extract was studied. Different amounts of banana peel
extract were incorporated into chitosan membranes. The study’s findings revealed that
the chitosan-banana peel extract composite membranes exhibited high antioxidant activ-
ity [
127
]. Essential oils from plants, used to make antimicrobial composites for food packing
and preservation, offer strong antioxidant activity and antibacterial capabilities [
128
]. Ac-
cording to a study, adding essential oils (clove, oregano, cinnamon, or eucalyptus oil) to
chitosan increased antibacterial efficacy in food packages. Chitosan-based active packaging
ideas were created because of its antibacterial action to limit, block, or postpone the growth
of microbes and extend the product’s postharvest/post-manufacturing shelf life [129].
4.4. Utilization of Chitosan-Based Composite in the Monitoring of Freshness/Spoilage
Food quality is a crucial factor in the food supply chain. Several analytical techniques
for evaluating food quality, including chromatography and mass spectrometry, are costly,
complex, heavy, and immobile. A quick detection technique uses biosensors with great
sensitivity, quick reaction times, compact sizes, low costs, and mobility. Furthermore,
biosensors are frequently employed to identify nutritional components and dangerous
ingredients in food [
130
]. Hydrogels constructed from chitosan are materials for the
manufacture of biosensors and indicators. As a result, they have a broad spectrum of
potential uses in the food manufacturing industry, such as evaluating food quality. pH
Polymers 2023,15, 3150 11 of 22
value is a crucial indicator frequently used to assess the degree of food decomposition and
freshness in the supply chain.
Based on pH, an effective, sensitive, and low-cost chitosan/corn starch hydrogel
film-embedded extract from Brassica oleraceae was prepared as a pH visual indicator. It
exhibits a distinct color as fish spoils due to its strong sensitivity to pH changes. Buyers
can use a noticeable color shift to quickly indicate the fish’s quality in the packaging [
131
].
According to Ebrahimi et al., a hydrogel pH indicator of chitosan was made that contains
anthocyanins and can be utilized to assess how fresh milk is. Lactic acid is formed during
storage by the lactic acid bacteria, which causes the pH of the milk to fall. The findings
demonstrated that the pH indicator, which serves as a reliable test of the freshness of milk,
changed from blue to violet rose after 48 h of milk storage [132].
5. Application of Chitosan-Based Composite in the Biomedical Industry
Chitosan has been used in the biomedical industry for its various benefits, including
minimal immunoreactions, strong biocompatibility, simple biological degradability, great
mucoadhesion, and natural abundance [
8
]. However, chitosan’s limited water solubility
is a problem that restricts its biomedical value, particularly under physiological circum-
stances where it is weakly soluble and has poor absorption [
133
]. Furthermore, chitosan
has a very poor transfection efficiency and lacks numerous beneficial characteristics, sig-
nificantly restricting its use range. To increase the water solubility of chitosan, it may be
blended with other compounds that improve the potential of chitosan to be utilized in
therapeutic applications [134].
Surprisingly, it has been shown that the blending of compounds with chitosan not
only improves the structural characteristics but provides some new characteristics. Because
of the distinctive structure of chitosan, it may go through various reactions including
phosphorylation, crosslinking, reduction, oxidation, complexation, halogenation, and acy-
lation, which are mainly responsible for new characteristics [
135
]. As a result, chitosan
and its derivatives are well known for their adaptable biological and chemical properties.
Compared to native chitosan, their functionalized analogs construct self-assembling nanos-
tructures more readily and quickly than native chitosan. The construction of hydrophobic
equivalents with amphiphilic qualities and chemical groups with various therapeutic and
active substances increased the bioactivity and DNA complexing capabilities [
136
]. Chi-
tosan was additionally identified as an antibacterial agent. It is hypothesized that chitosan
increases the movement of Ca++ from anionic sites of the bacterial cell membranes, which
causes cell damage. It also prevents plaque against Porphyromonomas gingivalis,Prevotella
intermedia, and Actinobacillus actinomycetemcomitans [
137
,
138
]. While generally harmless
to mammals, chitosan possesses a broad spectrum of action against gram-negative and
gram-positive bacteria. The chitosan and its composite characteristics show their potential
to be utilized in the biomedical sector, and a more thorough explanation is provided below.
5.1. Utilization of Chitosan-Based Products in Drug Delivery
Chitosan is a nontoxic and adsorbable polymer and reduces medication irritability;
thus, it is preferred in drug administration [
139
]. Chitosan hydrogels have been exten-
sively studied for their potential as a drug delivery method due to their biocompatibility,
biodegradability, and capacity to regulate drug release. Chitosan hydrogel was used
to encapsulate diclofenac sodium salt [
140
]. For topical use in wound healing, genipin
crosslinked porous chitosan fiber has been produced [
141
]. To cure diabetes, chitosan
hydrogels have been produced [
142
,
143
]. Different fatty acids, N-isopropyl acrylamide,
and 2-acrylamide-2-methylpropane sulfonic acid are used to create a chitosan-amide-
crosslinked matrix [
142
]. Phan et al. used a straightforward dropping method to form
insulin-loaded hydrogel beads. The insulin was enclosed in stacked double hydroxides and
covered with chitosan and alginate to make the hydrogel beads. The beads successfully
protected insulin from acid, releasing it gradually in the small intestine [
143
]. Using the
salt leaching method, metformin nanoparticles are blended into a chitosan/PVA polymeric
Polymers 2023,15, 3150 12 of 22
composite [
144
]. This technique creates a porous structure that enables the medicine to be
released under regulated conditions; the release rate is based on the size and distribution
of the pores inside the composite. Chitosan has been used as bioadhesive beads to increase
drug retention in the stomach while delivering medications to the stomach [
145
]. Chitosan
hydrogels can be used as cancer therapy tools to deliver specific drugs. The hydrogels
can be used to deliver anticancer medications such as cytarabine [
146
], methotrexate [
147
],
5-fluorouracil [
148
,
149
], doxorubicin [
150
,
151
], and cisplatin [
152
] directly to cancer cells.
Li et al. created a thiolated chitosan hydrogel with a gelation point of 37
◦
C to target
and treat a solid tumor. The negatively charged surface of the liposome electrostatically
interacted with the positive charge of chitosan, extending the gelation period when the
liposome-encapsulated curcumin was added [153].
5.2. Utilization of Chitosan-Based Products in Tissue Engineering
Chitosan composite-based scaffolds have been reported to be employed for tissue
engineering during the past several years due to their cationic properties and ability to
produce linked porous structures [
154
]. For bone repair and reconstruction, chitosan is
coupled with other biomaterials like hydroxyapatite and bioactive glass-ceramic to gener-
ate a carbonated apatite layer that improves the structural integrity of the bone [
155
–
157
].
Chitosan-based composite can be utilized to enhance bone regeneration by delivering
growth factors or medications directly to the location of the damage or by offering a
biomimetic template for the formation of new bone tissue. Extracellular matrix (ECM)
components are produced more readily when chitosan is present. ECMs like collagen
are necessary for bone formation and repair [
158
]. Even though chitosan is a promising
material for many medicinal purposes, it cannot be used to create bone tissue engineer-
ing. Chitosan lacks the osteoconductive qualities of real bones and is not robust enough
to withstand the weight-bearing needs of bone implants. Therefore, chitosan has been
combined with other biopolymers, including chitin, silk, and polycaprolactone, as well
as bioactive nanoceramics like hydroxyapatite and zirconia, to generate bio-composites,
which have been used by researchers to overcome these constraints [
159
,
160
]. These bio-
composites are more suitable for bone tissue engineering applications because they have
increased mechanical strength and structural integrity [
161
]. A dual network hydrogel for
articular cartilage regeneration was created by Liu et al. using thiolated chitosan and silk
fibroin. The composite had spontaneous gelling and excellent injectability in response to
pH and temperature. Chitosan increased strength and stiffness, whereas silk fibroin was
primarily responsible for elasticity. The platform supported chondrocyte proliferation and
encouraged the deposition of chondrocyte-specific matrix [162].
Chitosan-based hybrid systems may be used for cardiac tissue engineering [
163
].
Human cardiac ECM, chitosan, and gelatin were used by Lv et al. to build a 3D scaffold for a
tissue-engineered heart patch [
164
]. In a study, an injectable thermosensitive hydrogel made
of chitosan, dextran, and
β
-glycerophosphate loaded with mesenchymal stem cells from the
umbilical cord was described to treat myocardial infarction [
165
]. Mombini et al. created
electrospun cardiac conductive scaffolds using polyvinyl alcohol, chitosan, and various
concentrations of carbon nanotubes [
166
]. A polycaprolactone (PCL)/chitosan membrane
was combined with chitosan nanoparticles (CSNPs) to provide a biodegradable scaffold for
growing ocular cells. The scaffolds were brittle when they were dry but following a brief
immersion in phosphate-buffered saline, they were flexible and simple to handle. Scaffolds
with a CSNP/PCL ratio 50/25 exhibited the highest degree of transparency. The discovered
scaffold was nontoxic and encouraged corneal epithelial cell proliferation [167].
5.3. Utilization of Chitosan-Based Products in Wound Healing
The appropriate wound dressing must be placed to protect the wound site from ex-
ternal mechanical and microbiological stress to speed up the healing process. Traditional
dressings made of cotton, dressings, and gauze sometimes fall short of offering a moist and
hospitable environment and might hurt when removed because of wound drainage [
168
].
Polymers 2023,15, 3150 13 of 22
Chitosan has the potential to be utilized in wound healing. The usage of chitosan-based bio-
materials for wound healing applications has grown, either on their own or in conjunction
with other organic or synthetic biomaterials. Chitosan-based biomaterials have been uti-
lized for the dressing of wounds because of oxygen permeability and biocompatibility [
169
].
In wound healing, the impact of chitosan biomaterial on collagen production has been
investigated [
170
]. In another study, silver nanoparticles have been functionalized with
chitosan utilizing an ethanolic buds extract of Sygyzium aromaticum. The results revealed
that at relatively high concentrations of CS-AgNP, there is a drop in fibrinogen level and a
decrease in platelet aggregation. It has been demonstrated that CS-AgNP may be employed
as an efficient antibacterial agent and anticoagulant with minimal toxicity in the biomedi-
cal sector [
171
]. A porous sponge-like dressings material was prepared by freeze-drying
water-soluble adenine-modified chitosan derivative [
172
]. The intention was to address the
problem of bacterial infections, which can obstruct healing and cause significant tissue dam-
age during the early stages of wound healing. To create sticky chitosan hydrogels inspired
by mussels, Sun et al. developed sticky chitosan hydrogels that exhibited outstanding
mechanical strength and sustained dynamic adherence to biological surfaces and could be
utilized as dressings material in the wound healing process. Chitosan-gallic acid hydrogel
exhibited wound healing and hemostatic characteristic. Additionally, the hydrogel showed
improved antibacterial activity against E. coli and S. aureus and high biocompatibility [
173
].
The application of various chitosan-based composites in the food and biomedical sector
has been listed in Table 1.
Table 1.
The representative applications of various chitosan-based composite in the food and biomed-
ical sectors.
Sr. No. Chitosan Composite Application Ref.
1. Chitosan and curcumin-based film
The composite improved the shelf life of Schizothoraxpranati fillets and
prevented protein degradation, delayed lipid oxidation, and the
production of volatile amines
[99]
2.
Chitosan nanoparticle-based coating
containing cinnamon-perilla essential oils
and anthocyanidins
Protected the Red Sea Bream fillets from oxidation and
amine development [100]
3. Chitosan and tea polyphenols-based film Delayed the lipid oxidation in shrimps during storage (28 days) [102]
4. Chitosan, pomegranate peel extract, and
thymus essential oil-based film Increased the shelf life of fresh beef [112]
5. Chitosan, oregano, and thyme essential
oils-based film
Inhibited the proliferation of psychrophilic bacteria and increased the
shelf life of meat [114]
6. Chitosan/nano-titanium dioxide-based film Decreased deterioration and water loss while delaying respiratory
peaks in mangoes [123]
7. Chitosan/starch-based film The film exhibited antibacterial properties and prevented water loss
from grapes [124]
8. Chitosan/corn starch hydrogel
film-embedded extract from Brassica oleraceae
Acted as a pH-based sensor and exhibited a distinct color as fish
spoils due to its strong sensitivity to pH changes [131]
9. Chitosan/PVA polymeric composite Aided in the regulated release drugs [144]
10. Thiolated chitosan and silk fibroin hydrogel The platform supported chondrocyte proliferation and encouraged
the deposition of chondrocyte-specific matrix [162]
11. Human cardiac ECM, chitosan, and
gelatin composite Used as a 3D scaffold for a tissue-engineered heart patch [164]
12.
Chitosan, dextran, and β-glycerophosphate
hydrogel loaded with mesenchymal
stem cells
Used for the treatment of myocardial infarction [165]
13. Chitosan-gallic acid hydrogel Exhibited wound healing and hemostatic characteristic [173]
6. Miscellaneous
Chitosan produces many nanostructures, such as nanoparticles, nanohydrogels,
nanofibers, and nanocomposites. These structures are used effectively as nanocarriers
Polymers 2023,15, 3150 14 of 22
for enclosing bioactive compounds [
174
]. It has been demonstrated that chitosan and its
derivatives exhibit broad-spectrum antibacterial activity and can be used as an antimicrobial
agent [
175
]. Chitosan can also be used as a food additive to improve product sensory
quality and shelf life [
176
]. In addition to the abovementioned application, chitosan is a
thickener, emulsifier, and substitute for low-calorie foods [
177
]. Chitosan tends to increase
the viscosity of the continuous phase, making it more difficult for dispersed particles
to diffuse and slowing the rate of droplet aggregation [
178
]. This quality is used while
creating items like sauces, sweets, and ice cream. Chitosan may be used to clarify fruit
juices [
179
,
180
], beer [
181
], and purify water [
182
]. Chitosan has been proposed as a
functional additive for food and feed products [
183
]. Chitosan has several positive health
effects, such as lowering blood cholesterol and blood pressure, scavenging reactive oxygen
species, shielding against infections, controlling arthritis, enhancing anticancer properties,
and regulating inflammation [
183
]. Chitosan can also be used as a carrier for encapsulating
probiotic components because of its great biocompatibility, emulsifying capability, and
hypoallergenic [178] and hypocholesterolemic [184] characteristics.
Gamma irradiation was used to create hydrogels based on various ratios of chitosan
and sodium alginate, while glutaraldehyde served as a crosslinking agent. These hybrid
hydrogels were discovered to have great water swelling and high heat stability. This
research also examined the ketoprofen drug’s pH-sensitive release characteristics [185].
Chitosan is used as a drug delivery method for treating brain tumors and neurological
illnesses. Due to various characteristics of chitosan nanoparticles, such as efficient absorp-
tion by tumor cells and nasal mucosa, regulated release, low toxicity, biodegradability, and
biocompatibility, it has efficiently treated brain illnesses [186].
Chitosan composites may be used for treating burns, for the development of artificial
kidneys, as a blood anticoagulating agent, and for tendon or blood vessel engineering [
187
].
Crosslinking processes modulate the three-dimensional structures of chitosan and increase
chitosan utilization in the biomedical sector [
187
]. Separating and purifying physiologi-
cally active molecules using chitosan biopolymers because they include hydroxyl groups
and electron-donating amino is possible. Recent research has shown that chitosan-based
compounds are useful for preventing the growth of biofilms and reducing the virulence
of certain harmful bacteria [
188
]. Chitosan acts as a dental adhesive, a component of
dentifrices (toothpaste, chewing gum) with antibacterial properties, an agent to prevent
dental disorders, an agent to increase salivary secretion, etc. [
189
], while adding suitable
organic or inorganic elements might enhance the effects of chitosan on periodontal regenera-
tion [
190
]. This is due to the complicated periodontal microenvironment, which necessitates
a multi-component platform to accommodate its diverse compositional and mechanical
requirements for effective regeneration [
191
]. Polymethyl methacrylate was modified
with chitosan salts or chitosan-glutamate to create a novel antifungal denture base mate-
rial [
192
]. To control the medication delivery systems, pH-sensitive polymeric materials
were developed by sodium alginate, attapulgite, and chitosan-g-poly (acrylic acid) [193].
7. Conclusions
Chitin is the primary source of chitosan. Sources of chitin include the exoskeletons
of crustaceans, green algae, fungus, and the cuticles of insects. Crustacean shells are the
main source of chitin utilized in industry. Different chemical methods, including decalci-
fication, deproteinization, decolorization, and deacetylation, are used in the commercial
manufacturing of chitosan. Acidic and alkali treatments are damaging the environment.
Therefore, there is a need to determine the biological methods that may be used to produce
chitosan. Chitosan and its composites have the potential to be utilized in food preservation
because of their various biological properties. However, its utilization is limited due to its
poor solubility and poor mechanical characteristics. Chitosan composite films and coatings
can improve the shelf life of foods by suppressing bacterial populations and deterioration
reactions. Even though numerous studies on the development of chitosan composites
have been undertaken, more studies are needed to identify novel chitosan blends that can
Polymers 2023,15, 3150 15 of 22
enhance food quality and be used commercially. The stability of chitosan films at elevated
temperatures is questionable. However, nanotechnology-based approaches may improve
the efficacy of bioactive chitosan films and coatings and aid in developing stable, scalable
hybrid materials. Chitosan-based nanocomposites have low toxicity, mucoadhesiveness,
regulated release, biodegradability, biocompatibility, and efficient absorption properties,
making them a potential biomedical industry candidate.
Author Contributions:
Conceptualization, B.G.P., B.S.S., T.J.J. and C.C.; methodology, A.K.; software,
J.P.; validation, A.K., J.P. and S.Y.; formal analysis, B.G.P. and B.S.S.; investigation, B.G.P., B.S.S., T.J.J.
and C.C.; data curation, A.K., J.P. and S.Y.; writing-original draft preparation, A.K., J.P. and S.Y.;
writing-review and editing, A.K., B.G.P., B.S.S., T.J.J. and C.C.; visualization, A.K.; supervision, B.G.P.;
project administration, B.G.P.; funding acquisition, C.C. All authors have read and agreed to the
published version of the manuscript.
Funding: This project was partially supported by Chiang Mai University, Chiang Mai, Thailand.
Institutional Review Board Statement: Not applicable.
Data Availability Statement: Not applicable.
Acknowledgments:
B.S.S. and C.C. wish to thank Chiang Mai University, Chiang Mai, Thailand, for
its support. B.G.P. wish to thank Ganpat University, India, for its kind support.
Conflicts of Interest: The authors declare no conflict of interest.
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