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ES Materials and Manufacturing
DOI: https://dx.doi.org/10.30919/esmm5f828

A Review in Investigation of Marine Biopolymer (Chitosan) for

Bioapplications
Ishraq Abd. Ulrazzaq Kadhim,1 Hayder Abbas Sallal2 and Zainab S. Al-Khafaji3,*

Abstract
Recent studies have used more marine-origin polysaccharides since they are widely available, economical, biocompatible,
and biodegradable. These characteristics promote their technological use in water treatment, tissue engineering, cancer
therapy, wound dressing, drug delivery systems, and biosensors. Due to its versatility and capacity to be produced from waste
marine crustaceans, chitosan is becoming more and more important in a range of fields. It is first utilized in biomedical
applications due to its versatile properties, which include biocompatibility, antibacterial activity, and biodegradability. A
summary of marine polysaccharides (chitosan), including its supply, chemical, biological characteristics, and uses in tissue
engineering, is given in this review.
Keywords: Marine Biopolymer; Chitosan; Tissue Engineering.
Received: 22 October 2022; Revised: 29 November 2022; Accepted: 26 February 2023.
Article type: Review article.

1. Introduction function of the cells in biological systems.[12] Proteins,

Renewable biomaterials are one sustainable strategy to reduce polysaccharides, polynucleotides (silk, gelatin, elastin, chitin,
waste production and environmental degradation.[1–5] In recent chitosan, alginate) are the three main categories of natural
decades, the bioeconomy and biotechnology have polymers.[13] The utilization of natural polymers as structures
continuously advanced to creative and inventive uses of in tissue engineering applications is appropriate biologically.
products made from biopolymers.[6] Natural materials have Therefore, natural drugs developed from marine sources are
been an important source of human life, both at the level of more effective and specific for treating a variety of human
food and also at the level of medicine as therapeutic materials ailments.[14] One of the requirements for engineering materials
to improve human life.[7] is the ease of manufacturing and extraction, and these qualities
Marine-derived biopolymers, which are used in tissue are characteristic of polymeric materials extracted from
engineering, are one of the numerous materials being marine materials.[15]
investigated and used as effective restorative therapy options Due to their inherent biocompatibility and biodegradable
for the treatment of bone deformities and/or regeneration of structures, Natural biopolymers have a wide range of uses
destroyed bone function.[8–10] They have several qualities that such as medicines and the manufacture of some surgical
make them perfect for use in the creation of bioengineering- instruments or implants. Additionally, these substances are
based technologies for medical purpose.[11] more readily accepted by institutions responsible for health
Natural polymeric materials are among the first surveillance, regulation, and inspection.[16]
biodegradable materials used in clinical medicine. Natural Marine biomaterials typically have biological
polymeric has superior interactions with cells due to their characteristics that encourage the development of a variety of
bioactive characteristics, which enables them to improve the novel bioactive substances with particular pharmacological
characteristics of relevance to the pharmaceutical sector. They
1 Department of Materials of Engineering/University of Technology, are also typically biodegradable and biocompatible.[17] Indeed,
Iraq. marine substances are unique because they exhibit crucial
2 Prosthetics and orthotics engineering department, University of Al
traits In the fields of pharmacy: a high bioavailability and the
Nahrain, Jadriya, Baghdad, Iraq. target affinity.[18]
3 Building and Construction Engineering Technology Department,
One of the most actively researched scientific disciplines
AL-Mustaqbal University College, Hillah 51001, Iraq. nowadays is tissue engineering, which involves implanting
*Email: [email protected] (Z. Kafaji)
biomaterials and has applications in tissue regeneration. The

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Review article ES Materials & Manufacturing

main goals of tissue engineering can be classified as biocompatibility, sustained release of drugs, and antibacterial
improving, sustaining, repairing, or restoring the function of activities, chitosan has gained a lot of attention in bone
various living tissues.[19] regeneration.[26]
Chitin is a widely prevalent biopolymer that It is found in
fungi and insects, algae, And the exoskeletons of crustaceans. 2. Chitosan
Less frequently seen in nature, chitosan is found in several 2.1 Sources and structure
fungus (Mucoraceae).[20] Historically, the majority of One of the important things to know is that natural materials
commercially available chitosan samples were made by come from residues of natural materials, such as chitin and
chemically deacetylating chitin derived from crustacean chitosan, for example. They come from the wastes of marine
sources.[21] Important bioactive substances, chitin and chitosan organisms. Therefore, it should be noted that natural materials
have numerous extremely effective functions, it includes are of a specific quantity.[27,28] The steps for manufacturing
wound healing, antioxidants, resistance against bacteria and chitin from natural materials are shown in the Fig. 1.
the elimination of some pollutants.[18] The process of producing chitin has three stages: the first
Chitin and its compounds have a variety of uses such in is to extract the protein through the alkaline solution, the
nutrition, pharmaceutical, packaging, cosmetic textile, and second step is to get rid of minerals through the acidic solution,
agricultural industries as they are renewable resources.[22] Less and the third step is to give the color. Each step is important
frequently seen in nature, chitosan is found in several fungus for the substance to acquire certain properties.[29] Another way
(Mucoraceae). In the past, the majority of commercially to produce chitin of excellent quality and purity is through
available chitosan samples were made by chemically enzymes and acids secreted by microorganisms.[30]
deacetylating chitin from crustacean origins.[23] Demand from Chitin is the largest amine polysaccharide polymer after
vegans has recently increased market interest in chitosan natural cellulose, and it was first known in mushrooms in the
derived from fungi. The rising interest in producing protein year (1811).[32] Although chitin strengthens the cell walls of a
from these sources has led to a rise in interest in production number of fungi, it is found in the skin and skeleton of snails,
from insect cuticles.[24] invertebrates, crustaceans and insects such as (crab, king crab,
Chitosan, a whitish, viscoelastic polysaccharide, is a crayfish, lobster, and shrimp as show in Fig. 2.
biodegradable and biocompatible polymer produced by Chitin and its compounds are of great economic value due
deacetylating chitin. Products manufactured from chitosan to their biological properties and their practical value in terms
that have had their fundamental structure changed to produce of applications, as well as the fact that they are biodegradable
polymers with different characteristics.[25] Because of its ideal and biocompatible polymers derived from renewable natural
properties, including environmental friendliness, superior sources.[34] In contrast to chitin, which is its parent polymer,

Fig. 1 Chemical and biological procedures are used to produce chitin and chitosan. Reproduced with the permission from [31],
Copyright 2019 Wiley Periodicals, Inc.

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Fig. 2 Sources of the chitosan. Reproduced with the permission from [33], Copyright 2014 Elsevier Inc.

chitosan is a semicrystalline De-N Estylated Symmetrical Primary amine group, together with primary and secondary
made up two randomly oriented monomer units.[35] groups of hydroxyl, are the reactive groups present in chitosan
In general, Chitosan is used in biomaterials, particularly for (C6, C3). Functional groups can also include acetamide and
delivery systems for drugs and in cooperation with other glycosidic linkages.[38] These functional groups enable
compounds to enhance their medicinal benefits.[36] Fig. 3 numerous changes that result in polymers with novel
indicate the procedure to prepare chitosan from chitin. characteristics and behaviors as shown in Fig. 4.

Fig. 3 Production chitosan from chitin. Reproduced with the permission from [37], Copyright 2000 American Chemical Society.

© Engineered Science Publisher LLC 2023 ES Mater. Manuf., 2023, 21, 828 | 3
Review article ES Materials & Manufacturing

2.2 Properties and applications of chitosan lower the molecular weight of chitosan, the higher the
2.2.1 Solubility, degree of deacetylation(ⅮⅮ) and solubility.[34]
molecular weight
Chitosan solubility affected by group of variables, Includes 2.2.2 Bioadhesiveness
molecular weight for polymer, deacetylation degree(ⅮⅮ), (PH) It's been proven that the swollen chitosan's adhesive abilities
sensitive, temperature, and crystallinity of polymer. Chitosan continue to work well even after numerous interactions
does not have the ability to dissolve in water and organic between both the basic surface and chitosan. This
solutions.[40] Since chitosan's pKa value is about 6.5, the demonstrates a number of other processes, including hydrogen
structure's abundance of protonated NH2 groups is what makes bonding and ionic interactions, may have assisted in the
it highly soluble in acidic aqueous conditions. Chitosan adhesion.[45] As an essential mechanism of action, one of the
dissolves when approximately (50%) of all amino groups are causes of adhesion is the interaction of positive ions with
protonated.[36] negative ions inside the material. Electrostatic interaction was
Another essential quality is molecular weight, which may discovered to be the main action mechanism at the molecular
work in conjunction with ⅮⅮ to increase the solubility of CS level.[46] Acknowledging how pectin subdomains are organized
biopolymers and explain certain seemingly contradictory can be crucial from a biomedical standpoint for modifying the
results.[41] The (ⅮⅮ) for the Chitosan is an important mucoadhesive, anti-metastatic, and cell adhesion
characteristic because earlier studies have demonstrated, the characteristics of pectin gels as well as for the creation of
Chitosan that have big (ⅮⅮ) reveals better decomposition (by sufficient mechanical gels.[47,48]
water) in addition to the biological characteristics.[42] Due to
bigger (ⅮⅮ) suggests that the amino groups are concentrated 2.2.3 Antimicrobial activity
more heavily within the polymer's, there are important It is vital for health care to identify alternatives to antibiotics
functional groups to show the biological properties and since bacterial resistance to antibiotics is a serious issue.
solubility of chitosan such as [-ΝΗ2].[43] In addition to ⅮⅮ, Antimicrobial action is provided by chitosan derivatives and
molecular weight (ΜԜ) is a crucial factor that affects chitooligo-saccharides against a variety of microorganisms,
chitosan's bioactivity. Higher (ΜԜ) chitosan rarely exhibits including bacteria, yeast, and filamentous fungus.[49] It is ideal
significant bioactivities compared to lower MW chitosan.[44] for potential uses in the food and pharmaceutical industries
There is a relationship between the molecular weight (ΜԜ) due to its many characteristics, including its antibacterial
and solubility in water and the biological properties where the characteristics, permeability, and solubility. It also minimizes

Fig. 4 The chemical modified in the structure of chitosan by functional groups. Reproduced with the permission from [39], Copyright
2000 American Chemical Society.

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swelling and enhances mechanical functionality.[50] making it a great potential medical material.[61]
After chitosan is removed from the surface, bacterial Chitosan has outstanding biocompatibility, Chitosan also
growth can occur, suggesting that chitosan has a growth- readily produces hydrogels using crosslinking techniques.[62] It
inhibitory effect. This is significant because resistant colonies has been found to be extremely biocompatible by analyses in
might develop if the cells become chitosan-adapted.[51] the biological field. Chitosan is also digested by some human
Chitosan was found to have a number of benefits over other enzymes, particularly lysozyme, and is thought to be
disinfectants, including more antibacterial activity, high biodegradable at the same time.[63]
mortality, and Less toxicity to the human body.[52] Bacterial
growth should not occur, and this is achieved through the 2.2.7 Application of chitosan
interactions that occur between the positively charged polymer It has numerous applications in the fields of medication
with some anionic components (such as sialic acid, neuraminic delivery and tissue engineering, including substrates for cell
acid and other compounds). Chitosan may cause a change in culture and vascular grafts made of cartilage, skin, and bone.
cell permeability if it has high (ΜԜ) and interaction occurs Chitosan is a bio-functional beneficial biomaterial because of
between them, or it may create an impenetrable barrier around its biologically renewable, biocompatible, biodegradable,
the cell, which would prevent the entry of vital solutes into thenon-toxic, and non-antigenic properties.[64] Chitosan can also
cell.[53] have its hydroxyl and amino groups chemically modified to
produce a wide range of chemical diversity. Additionally, it
2.2.4 Antioxidant activity exhibits bioadhesive characteristics.[65] The summarized
Due to the connection between oxidative stress and a variety applications of chitosan in tissue engineering exhibited in
of diseases, including Alzheimer's disease, Huntington's Table 1.
disease, amyotrophic lateral sclerosis, and cancer, antioxidants
Table 1. Chitosan applications in tissue engineering.
are growing in popularity. Additionally, it is connected to the
Natural Application in Media of culture Ref
consequences of other diseases like diabetes.[54]
biopolymer tissue
Chitosan's antioxidant property is one of its well-known
engineering
uses. Numerous studies have demonstrated that chitosan
chitosan Bone tissue Vitro (Mouse BMSCs) [66]
prevents lipid oxidation in dietary and biological systems by
chitosan Neural tissue Vitro (PC12 neuronal [67]
inhibiting reactive oxygen species.[55] Through the donation of
cells)
a hydrogen atom or a pair of lone electrons, chitosan can
chitosan Neural tissue Vitro (Neural stem cells) [68]
deactivate free radicals or chelate metal ions. Adsorption, ion-
chitosan Nerve tissue Vivo (Rabbits) [69]
exchange, and chelation are just a few of the numerous
chitosan Bone tissue Vitro and in vivo (mouse [70]
processes that may take place when chitosan interacts with
calvarial, hPDLCs cell)
metal ions.[56] Chitosan's main functional groups for its
chitosan Nasal tissue Murine BV-2 [71]
antioxidant properties are the hydroxyl (OH) and amino (NH)
chitosan Bone tissue Vivo (rat calvarial) [72]
groups, however doing so can be challenging because of the
chitosan Bone tissue Vitro (hMSC cell) [73]
material's semi-crystalline structure and strong hydrogen
chitosan Bone tissue Vitro and in vivo(MC3T3- [74]
bonding.[57] Chitooligosaccharides have also underwent
E1 cell, rat femoral bone)
chemical alteration to increase their antioxidant properties,
chitosan mesenchymal Vitro (BMP-2) [75]
such as gallic acid or phenolic chemicals added to the
stem cells
polymers.[58]
chitosan cartilage Vivo (rabbit) [76]

2.2.5 Anti-inflammatory properties

The inflammatory process is the body's natural physiological 3. Conclusions and future perspectives
reaction to tissue destruction. The primary objectives for Natural polymers, usually apparent and sometimes invisible,
inflammation to occur, through occur a process of transfusion play a significant part in our daily lives. In contrast, Because
of white blood cells, takes place at the site of injury or of its various uses in the medical and food industries the
damaged tissue in order to destroy the dangerous pathogens natural polymers have attracted much more interest recently.
that appear in the tissues, if practical, and to initiate the process As a result, we may say that the topic of biopolymers is one
of healing.[59] that is hotly debated. Recent research indicates that chitosan is
among the most investigated based biopolymers. Chitosan has
2.2.6 Biocompatibility and biodegradability a broad range of uses owing to its bio-compatibility and bio-
Biocompatibility is the ability of a biomaterial to perform its degradability, with a focus on bio-medical engineering and
intended purpose in relationship to a therapeutic treatment drug-delivery systems. Among other applications, chitosan is
without resulting in any adverse Effects on the patient or utilized in agriculture, the farming industry, water purification,
recipient.[60] When a material is biocompatible, that indicates the control of pollution, videography, and the paper industry.
the material is no longer toxic and has no immune response The chitosan substrate can also contain a broad variety of

© Engineered Science Publisher LLC 2023 ES Mater. Manuf., 2023, 21, 828 | 5
Review article ES Materials & Manufacturing

additional forms, including antiviral medications, proteins, [9] N. S. Radhi, N. E. Kareem, Z. S. Al-Khafaji, N. M. Sahi, M.
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necessary in future. and Technology, 2018, 9, 468-474.
[11] K. Su, C. Wang, Recent advances in the use of gelatin in
Acknowledgments biomedical research, Biotechnology Letters, 2015, 37, 2139-2145,
This work was supported by Al-Mustaqbal University College doi: 10.1007/s10529-015-1907-0.
(grant number MUC-E-0122). [12] E. Sharifi, S. Ebrahimi-Barough, M. Panahi, M. Azami, A.
Ai, Z. Barabadi, A.-M. Kajbafzadeh, J. Ai, In vitro evaluation of
Conflict of Interest human endometrial stem cell-derived osteoblast-like cells’
There is no conflict of interest. behavior on gelatin/collagen/bioglass nanofibers’ scaffolds,
Journal of Biomedical Materials Research Part A, 2016, 104,
Supporting Information 2210-2219, doi: 10.1002/jbm.a.35748.
Not applicable. [13] B. D. Ratner, A. S. Hoffman, F. J. Schoen, J. E. Lemons,
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