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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5390_Библиотеки_им_академика_М_И_Перельмана.pdf
316 S. R. Benjamin et al.
Dr. Stephen Rathinaraj Benjamin is a
distinguished researcher and engineer renowned for his
profound knowledge and expertise in biosensor technology. He is primarily dedicated to advancing
the field of biosensors to create state-of-the-art technology for medical diagnostics and the monitoring of environmental conditions. His work encompasses the design of sensors capable of
detecting antibodies, the integration of nanomaterials, and the advancement of surface modification
techniques to optimize biomolecule interactions. His research is primarily directed towards medical
applications, with a strong emphasis on early disease detection and the exploration of innovative
treatment approaches. Notably, he is currently dedicated to the development of biosensors tailored
for immunosensors/Point of Care (POC) systems, specifically targeting the diagnosis and treatment
of neurodegenerative diseases.
Eli José Miranda Ribeiro Júnior is a highly accomplished professional with a strong academic
background in Environmental Management and Business Administration. He has excelled as a
university professor, sharing his expertise at prestigious institutions and teaching a wide range of
subjects including Administration, Accounting, and Civil Engineering. With his diverse skill set,
including expertise in team leadership, process improvement, and adaptability to complex
environments, he continues to make significant contributions to education as a Master Professor
at Faculdade Cgesp.
Professor, D
osa Fireman Dutra is a distinguished leader in the field of Biodevices and
r. R
Bioelectronics at the Laboratory of Biomedical Engineering and holds the position of Associate
Professor at the Federal University of Pernambuco in the Department of Biomedical Engineering,
Brazil. She has a solid educational background, having graduated in Electronic Engineering,
obtained an MSc in Biomedical Engineering, and earned a PhD in Biosensors and Immunosensors,
followed by a Postdoctoral in Analytical Chemistry. Her main area of expertise involves improving
the analytical capabilities of a wide range of sensor types, such as amperometric, capacitive,
impedimetric, piezoelectric, and optical transducer-based sensors.
Professor, Dr.
Geanne Matos de Andrade holds a degree in Pharmacy, a master’s, and a
doctorate in Pharmacology from the Federal University of Ceará (UFC), with a post-doctorate in
Neuroscience from the University of Coimbra, Portugal. She is a Full Professor in the Department
of Physiology and Pharmacology at UFC, Fortaleza, Ceará, a 1C research productivity fellow, and
serves on several key committees, including the Central Analytical Management Committee, UFC
PRINT Program, and the Chamber of Biological and Environmental Sciences of FUNCAP.
Currently, she is the Assistant Coordinator of Professional Postgraduate Programs at CBII of
CAPES. She has held prominent roles, such as Coordinator of the Pharmacology Postgraduate
Program and the Graduate Program in Medical Sciences at UFC, as well as UFC’s Research
Coordinator. She teaches Neurophysiology in Medicine, Pharmacy, Nursing, Biological Sciences,
Psychology, and Biology, while also mentoring and leading courses in the Postgraduate Programs
in Pharmacology and Medical Sciences. Her research focuses on experimental
Neuropsychopharmacology, specializing in neurodegenerative diseases like Parkinson’s and
Alzheimer’s, cerebral ischemia, neuroprotection with natural compounds, and purinergic signaling.
Cellulose, Chitin, and Chitosan Composite-Based Sustainable Biomaterials
13
Sultan Gul , Yesim Karahan
, Ozan Baris Kurtur ,
and Yasemin Budama-Kilinc
Abstract
The escalating environmental concerns highlight fears about the sustainability of
our planet’s livability. Synthetic polymers, widely used across industries, are
major contributors to these issues due to their poor biocompatibility, potential
toxicity from degradation, and sustainability challenges in production and disposal. To address these issues, researchers are turning to green biomaterials
derived from renewable natural sources, crucial for developing bioactive and
biodegradable materials.
Among natural polymers, cellulose, chitin, chitosan, and their derivatives
stand out in drug delivery systems due to their biocompatibility, biodegradability,
accessibility, modifiabil ity, non-toxicity, and stability against environmental
factors. Cellulose, abundant in plant cell walls and sourced from various natural
origins, offers structural integrity through intermolecular hydrogen bonding.
Chitin, found in crustacean shells, and its derivative chitosan, known for its
cationic nature and unique properties like antimicrobial activity, they are also
prominent.
Chemical modifications enhance these biopolymers’ solubility and
interactions, enabling their integration into innovative composites. Combining
cellulose and chitosan has yielded materials with enhanced functionality, suitable
for diverse biomedical applications such as films, aerogels, and membranes.
O. B. Kurtur
Graduate School of Natural and Applied Science, Bioengineering Department, Yildiz Technical
University, Istanbul, Turkey
Y. Budama-Kilinc (
Faculty of Chemical and Metallurgical Engineering, Department of Bioengineering,
Yildiz Technical University, Istanbul, Turkey
Health Biotechnology Joint Research and Application Center of Excellence, Istanbul, Turkey
#
The Author(s),
R. Malviya, S. Sundram (eds.), Sustainable Green Biomaterials As Drug Delivery
Systems, Biomaterials, Bioengineering and Sustainability 1,
https://doi.org/10.1007/978-3-031-79062-1_13
✉)
under exclusive license to Springer Nature Switzerland AG 2025
317
318 S. Gul et al.
These biopolymer composites exhibit 1D to 3D structures, leveraging cellulose’s
hydrophilicity and mechanical strength alongside chitosan’s antimicrobial
properties.
The growing interest in these sustainable biomaterials stems from their biodegradability and eco-friendl iness, offering viable alternatives to conventional
petroleum-based products. This chapter provides an overview of cellulose, chitin,
and chitosan, discusses their production, and explores recent advancements in
their application as green polymers in drug delivery systems, showcasing their
potential to address environmental challenges while advancing biomedical
technology.
Keywords
Sustainable Green Biomaterials · Cellulose · Chitin · Chitosan · Drug delivery
13.1 Introduction
In today’s world of material science and engineering, there is a growing need for
sustainable solutions (Apelian
tent
in composition, synthetic polymers often lack biocompatibility and pose toxicity
risks from degradation products. Moreover, the production sustainability of synthetic polymers and increasing concerns about the environmental impacts of synthetic polymers, including microplastic problems and disposal, have led researchers
to investigate alternative polymer sources (Kostag and El Seoud 2021; Muhamad
al. 2014). For these reasons, the exploration and use of biopolymers derived from
et
renew
able resources have become a significant focus in the search for green sustainable materials. Among these biopolymers, cellulose, chitin, and chitosan stand out
due to their natural abundance and desirable properties. Cellulose, as the predominant biopolymer found on Earth, plays a crucial role in the construction of plant cell
walls, enhancing their remarkable strength and stability (Heinze 2016).
On the
other hand, chitin and its derivative, chitosan, are present in the
exoskeletons of crustaceans and insects. They have unique properties like biocompatibility, biodegradability, antimicrobial properties, and wound-healing
capabilities, making them invaluable in various biomedical, pharmaceutical, and
environmental applications (Tao et al. 2020). Moreover, they are renewable and
have
minimal environmental impact, making them highly desirable for sustainable
material development (Nadeem et al. 2020).
Blending di
fferent polymers is a technique employed to produce innovative
composites with tailored properties (Kulshreshtha and Vasile 2002). This technique
offer
s a technological avenue to create customized composites, enhancing processability and yielding superior properties compared to individual polymers (DíezPascual 2019 ). For instance, cellulose, chitin, and chitosan can be combined with
c
omposite materials, and this new composite offers many advantages. These
composites inherit each biopolymer’s individual properties while exhibiting
2012). In particular, while cost-effective and consis-
13 Cellulose, Chitin, and Chitosan Composite-Based Sustainable Biomaterials 319
enhanced mechanical strength, flexibility, and biodegradability (Kestur 2010;
Kochkina and Lukin
be improved by incorporating additives, nanomaterials, and functionalization
strategies. In this way, they can be used in various fields, from biodegradable
packaging materials to tissue engineering scaffolds, biomedical implants, drug
delivery systems, water purification membranes, and environmental monitoring
sensors (Pal et al.
multifunctional, biodegradable composites for various uses like films, foams, fibers,
and filters, including biomedical research and potential in vivo applications (Kostag
and El Seoud 2021). Each application leverages the unique properties of cellulose,
chitin, and chitosan composites to address societal and environmental concerns
while advancing the paradigm of green, sustainable materials (Anwer et al.
In this context, inte
represents a pioneering approach in sustainable biomaterials research. In the past few
years, there has been rapid advancement in the utilization of composites made from
sustainable biomaterials extracted from cellulose, chitin, and chitosan, serving as
eco-friendly polymers in drug delivery systems. By harnessing the abundance and
versatility of these biopolymers, resea
in material science, usheri
and socially responsible innovations.
In this chapter, we will briefly overview the molecular structures of cellulose,
chitin, and chitosan. We will then discuss the manufacturing process of compositebased biomaterials utilizing these three substances. Lastly, we will discuss the latest
advancements in applying cellulose, chitin, and chitosan composite-base d
eco-friendly biomaterials as sustainable polymers in drug delivery systems.
2020; Yadav et al. 2023). Furthermore, these composites can
2021; R
izvi et al. 2022).
grating cellulose, chitin, and chitosan into composite materials
ng in a future characterized by environmentally friendly
This
approach fosters
rchers and engineers can unlock new frontiers
the production of
2023).
13.2 General Structures of Cel lulose, Chitin and Chitosan
13.2.1 Cellulose
Cellulose is a natural material found in various sources such as plants, animals,
algae, fungi, and minerals (McNamara et al. 2015). Nevertheless, plant fiber is the
primary origin of cellulose. Cellulose is an important component of the cell walls of
plants, making up about 40% of the carbon fraction. It provides structural support
and is often found with other substances, such as hemicelluloses, lignin, and minor
quantities of extractives. While cellulose can exist in a pure form in plants, it is more
commonly found in conjunction with other substances (Heinze 2016)
Cellulose is a polymer formed by “polycondensation” (Abrahamsen-Mills and
Small 2021). It consists of D-glucopyranose ring units in the 4C1-chair configuration, the conformation with the lowest energy. These units are connected by
β-1,4-glycosidic bonds, which lead to a 180° alternation in the direction of the
cellulose chain (Gopi et al. 2019). Each anhydroglucose unit (AGU) in the cellulose
chain contains three reactive hydroxyl groups: a primary group at C6 and two
secondary groups at C2 and C3, all located in the ring’s plane (Heinze
.
2016).
Its
320 S. Gul et al.
Fig. 13.1 Chemical structures of chitin-chitosan-cellulose and their natural source. Deacetylation
of chitin to chitosan
molecule has two chemically different chain ends. One end contains an anomeric C
atom linked by the glycosidic bonds, also known as the non-reducing end. The
reducing and non-reducing ends of cellulose chains make them directionally asymmetric molecules. At the other end, a D-glucopyranose unit is in equilibrium with the
aldehyde function, serving as the reducing end group (Fig. 13.1). Cellulose’s
molecular structure can undergo modification through reactions such as hydrolysis
or oxidation of the cellulose chain. These reactions primarily take place either on the
surface of the fibrils or within the amorphous regions (Heinze
2016).
The chemical reactivity of cellulose is dependent on its polymorphic structure.
The less-ordered amorphous regions exhibit higher reactivity compared to the
highly-ordered crystallite regions (Heinze
2016). Inaugural chemical reactions
occur primarily on the surfaces of the less-ordered fibrils, while the impenetrable
crystalline structure has minimal impact. Despite its moisture-absorbing ability,
cellulose remains insoluble, yet it can undergo distensioning in water, diluted acid,
2023;
and some solvents (Etale et al.
Wohlert et al.
2022). Solutions with low pH
values can render cellulose soluble, albeit at the cost of significant degradation via
acetal (glycosidic) hydrolysis. Alkaline solutions cause hemicelluloses to swell and
dissolve within cellulose (Przypis et al. 2023). Strong alkaline solutions can penetrate cellulose through swelling and capil lary attraction, a mercerization process
activating it for cellulose ether production. In basic media at elevated temperatures
(>150 °C), cellulose undergoes hydrolysis, and oxidation may occur (Stephen and
2016).
Phillips
Microbiological degradation happens through enzymatic hydrolysis,
leading to the cleavage of the B-1,4-glucosidic linkages (Lakhundi et al. 2015).
Chemically modified cellulose ethers, due to steric hindrance, are less susceptible to
enzymatic degradation, exhibiting significantly improved stability. Furthermore,
amorphous cellulose is more prone to enzymatic hydrolysis than highly crystalline
13 Cellulose, Chitin, and Chitosan Composite-Based Sustainable Biomaterials 321
cellulose. Breaking down natural cellulose with a combination of enzymes leads to
products that offer specific practical benefits, such as enhanced solubility (Stephen
and Phillips
2016).
13.2.2 Chitin
Chitin is the second most abundant natural polymer after cellulose (Barbosa et al.
2019; Elieh-Ali-Komi and Hamblin 2016). The term “chitin” originates from the
Greek word “chiton, ” which refers to a coat of mail or armor. Chitin is mainly
derived from insects like cuticles, beetle cocoons, and ovipositors, as well as from
crustaceans such as shrimp shells and crab shells (Kostag and El Seoud 2021).
Squids like Loligo stomach, centric diatoms such as algae and Thalassiosira
fluviatilis, and fungi like Aspergillus nidulans and Mucor rouxii are also significant
sources of chitin (Kaur et al. 2023). Chitin is characterized by its chemical structure
(1→4)-2-acetamido-2-deoxy-β-d-glucan, and composed of N-acetylglucosamine
units that form a linear array with a molecular weight of 2–3 million Daltons
(Ahmad et al. 2020). These N-acetylglucose units in chitin are rotated 180° with
respect to each other, forming the disaccharide N,N´-diacetylchitobiose, similar to
cellulose. Despite the enzymatic hydrolysis of chitin yielding N-acetylglucosamine
and glucosamine, solid-state NMR analysis sugges ts little to no presence of glucosamine (Elieh-Ali-Komi and Hamblin 2016). Glycosidic bonds in chitin that form
between modified monomeric glucose molecules are responsible for its structure.
This long chain of chitin can form a solid structure in an insect’s wings or a clam’s
shell (Nicolay et al. 2020).
Chitin tends
sometimes exceeding 0.5μm and bundled in groups of 10 or more. X-ray diffraction
analysis reveals three crystalline modifications of chitin—α-, β -, and γ-chitin—
differing in hydration, unit cell size, and chitin chain arrangement (Blackwell
1988). α-chitin exhibits antiparallel chain orientation, β-chitin features parallel
chain arrangement, and γ-chitin is characterized by two parallel strands alternating
with a single antiparallel strand. Furthermore, non-crystalline transient states have
been noted in fungal chitin (Hou et al.
antiparallel chains contributes to its higher resistance to hydrogen bond disruption.
Beta-isoforms, as observed in squid, display enhanced solubility, affinity, and
reactivity towards solvents due to the weaker hydrogen bonding between chains.
The third chitin isoform is γ-chitin, which is a variant of α-chitin (Ahmad et al.
2020
In the crystalline structures of α- and β-chitin, α-chitin’s unit cell is ortho-
).
rhombic with chitobiose sections forming helical conformations. The unit cell of
β-chitin is monoclinic, exhibiting a helical conformation similar to α-chitin but
packed in a parallel arrangement. Unlike α-chitin, β-chitin chains form H-bonded
sheets along the a-axis, leading to increased swelling by solvents and enhanced
reactivity towards derivatization. This difference explains why β-chitin exhibits
more swelling and reactivity compared to α-chitin (Pillai et al. 2009; Salavati 2023).
to form microfibrils stabilized by hydrogen bonds, with lengths
2021).
Alpha chitin’s dense arrangement of
322 S. Gul et al.
Fig. 13.2 Schematic representation for the biological and chemical routes for producing chitin
In industrial chitin extraction, there are typically three primary stages:
(i) deproteinization, which involves the removal of proteins using aqueous solutions
of chemicals such as sodium hydroxide or potassium hydroxide;
(ii) demineralization, where acids like hydrochloric acid are used to eliminate
calcium carbonate; and (iii) decolorization, achieved through solvent extraction
with substances like ethanol or bleaching with hydrogen peroxide to remove
pigments. Alternatively, a biological route employing bacteria that produce protease,
followed by treatment with lactic acid, can be utilized for the first two steps, offering
reduced environmental impact (Fig. 13.2) (Younes and Rinaudo 2015).
13.2.3 Chitosan
Chitosan is a substance that can be obtained from through biological processes and
chemical methods (Rehman et al. 2023). For example, the microbial synthesis of
chitosan is a biological pathway that involves various organisms such as
Phycomyces blakesleeanus. Chitosan is produced through the utilization of cell
cultures from these organisms, with the addition of Aspergillus niger to the culture
medium to facilitate the production process. This production mechanism also causes
deacetylation of chitin, and chitosan is obtained after an incubation period of 96 h
(Kuzgun and İnanlı 2013).
Chitosan, a linear polysaccharide, is created through the deacetylation process
of chitin, where the acetamide groups are hydrolyzed via potent alkaline treatment
13 Cellulose, Chitin, and Chitosan Composite-Based Sustainable Biomaterials 323
and is a naturally occurring substance found in only trace amounts within the
ecosystem, notably prevalent in select fungal species. It consists of 2-amino-2deoxy-β-D-glucopyranose linked through β (1–4) with 2-acetamino-2-deoxy-β-Dglucopyranose (Brasselet et al.
2019; Shariatinia 2019). It is shown that their turn to
each other by chit in’s deacetylation and chitosan’s acetylation in (Fig. 13.1). The
difference between chitin and chitosan lies in the degree of deacetylation (DA), with
chitosan having a DA higher than 50 mol% and being soluble in dilute acid solutions
(Younes and Rinaudo
alkalis, which
removes acetamide groups. This process involves several chemical
2015). Initially, chitin undergoes deacetylation using strong
steps, including demineralization, deproteinization, and deacetylation, which are
essential for extracting chitosan from chitin (Fig. 13.1) (Kumar et al. 2023). In
heterogeneous deacetylation, chitin is suspended in hot, concentrated alkali, whereas
homogeneous deacetylation involves suspending chitin in a concentrated base
2003)
followed by rapid cooling (Methacanon et al.
ation
applic
in the dissolution of chitin and in homogeneous deacetylation processes
. Ionic liquids have also found
(Ma et al. 2020). On the other hand, environmentally friendly enzymatic methods
employ chitin deacetylases to catalyze the hydrolysis of N-acetamido bonds in
chitin, leading to well-defined chitosan structures without degradation (Tsigos
et al. 2000).
Researchers have been interested in chitosan because of the amines present at
the C-2 position of glucosamine residues, which contribute key functional
characteristics to chitosan (Stephen and Phillips
2016). Hydroxyl at C3 and C6
and primary amine at C2 in every sequence make it highly susceptible to chemical
transformation (Nicolle et al. 2021 ). Due to their beneficial biological and filmforming properties, chitosan and its derivatives have emerged as an excellent
eco-friendly substitute for synthetic plastic polymers, which have found various
applications in the environment, packaging, and medical sectors (Jiang et al. 2023)
more, chitosan can be converted into a polycation with protonated amino
Further
groups, enabling it to interact with various natural or synthetic anionic species such
as lipids, proteins, DNA, and negatively charged synthetic polymers like poly
(acrylic acid). It is worth noting that chitosan is the sole naturally occurring polysaccharide that carries a positive charge (Pavinatto et al. 2010). Chitosan molecules
possess both amino and hydroxyl groups, enabling the formation of stable covalent
bonds through reactions such as etherification, esterification, and reductive
amination (Ibrahim and El-Zairy 2015)
ysico-mechanical attributes of chitosan, which are toxicity, solubility,
The ph
.
viscosity, reactivity of proteinaceous material coagulation, and heavy metal ion
chelation, are intricately linked to its molecular weight and the extent of
deacetylation. Notably, chitosan with heightened deacetylation levels displays a
nuanced toxicity profile contingent upon its molecular weight: it demonstrates
reduced toxicity at lower molecular weight (Román-Doval et al.
2023).
It still
exhibits heightened toxicity as molecular weight escalates. Conversely, chitosan
with diminished deacetylation levels is an absorption facilitator across a spectrum of
molecular weights. Furthermore, chitosan’s solubility and degradation kinetics are
intricately tied to its molecular weight profile, with higher molecular weight variants
.
324 S. Gul et al.
displaying decreased solubility and a more protracted degradation process compared
to their lower molecular weight counterparts (Román-Doval et al.
Neau 2001).
Moreover, the solubility of a substance in water is affected by the acidity or
alkalinity of the solution, which is measured by its pH level. Therefore, the solubility
of a substance in water can vary depending on the pH of the solution (Ibrahim and
El-Zairy 2015). Additionally, the solubility and degradation kinetics of chitosan are
closely linked to its molecular weight profile. Higher molecular weight variants
exhibit reduced solubility and undergo a slower degradation process compared to
their lower molecular weight counterparts (Román-Doval et al. 2023; Zhang and
Neau 2001). Furthermore, a substance’s solubility in water is influenced by the
acidity or alkalinity of the solution, as indicated by its pH level. Thus, the solubility
of a substance in water may vary depending on the pH of the solution (Ibrahim and
El-Zairy 2015). Chitosan readily dissolves in acidic aqueous solutions but remains
insoluble in both water and alkaline solutions (Blagodatskikh et al.
2023; Zhang and
2023).
13.3 Preparation of Cellulose, Chitin, and Chitosan
Composite-Based Biomaterials
Polymer composites can be classified as either fully or partially renewable,
depending on the origin and nature of the polymer matrix and reinforcement (Thakur
2014). Both reinforcement and matrix materials are incorporated and sourced
et al.
from bio-renewable resources in completely renewable polymer composites. Alternatively, only one element in partially renewable composites is sourced from
bio-renewable resources. For instance, the polymer matrix may be derived from
bio-renewable resources. At the same time, the reinforcement comes from
non-renewable resources, or the polymer matrix may be synthetic with the reinforcement originating from bio-renewable resources (Thakur et al. 2014). Chemical
modifications of cellulose/chitin/chitosan composites biopolymers often enhance
solubility and biological interactions (Kostag and El Seoud 2021). Three techniques
can be used to obtain a composite based on cellulose and chitin-chitosan (SilvaCastro et al. 2017).
1. Physical ways (Ultrasonication, thermal treatment, microwave, electrospinning,
etc.)
2. Chemical ways (Graft polymerization, catalysis, nucleophilic substitutions, etc.)
3. Biological ways (Biocatalysis, enzymatic hydrolysis, etc.)
13.3.1 Cellulose Composite-Based Biomaterials
Cellulose composites are made using diverse manufacturing techniques like compression moulding, injection moulding, resin transfer moulding, and vacuum bagging. The quality of composites is influenced by processing factors such as
13 Cellulose, Chitin, and Chitosan Composite-Based Sustainable Biomaterials 325
Fig. 13.3 Methods of fabrication of cellulose composite materials
temperature, pressure, and moulding time (Jaafar et al. 2019). Preheating natural
fibers to reduce moisture content is expected, though cellulose degradation at high
temperatures can harm mechanical properties (Vaca-Medina et al. 2013). Improper
fiber dispersion may lead to agglomeration, lowering tensile strength. The choice of
process technology is determined by factors like the product’s design, anticipated
performance, cost-effectiveness, and manufacturing simplicity. Different methods
13.3 (
for fabricating cellulose composites are shown in Fig.
Pattnaik and Swain
2022).
Pultrusion is an ongoing method for manufacturing composites. It involves pulling
resin-impregnated fibers through a die shaped to match the aspired cross-sectional
form of the creation. This method facilitates the production of slender formations
and various segmental configurations (X. Pe ng et al. 2012). Additionally, pultrusion
offers the potential for high levels of automation, making it advantageous for
manufacturing (Volk et al. 2022).
Hand L
aminati
on involves applying resin to fibers in a mould using rollers, often
assisted by vacuum bags to eliminate excess air and compact the part with atmospheric pressure. While this method offers simplicity, low tooling costs, and design
flexibility, it is time-consuming and lacks automation potential, which are its
primary limitations (Vallittu 2018).
Compression
Moulding stands as a prevalent technique for crafting composites
(Sahu et al. 2024). This method utilizes a partially processed compo site sheet or
sheet moulding compound, which is then shaped into final parts through