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3 Strategies in Synthesis of Biodegradable Polymers 61
various synthetic dyes, such as thiazole orange, Disperse Red 1, Rhodamine 6G,
Rhodamine B, and cyanine dyes, provides novel compounds with advantageous uses
in photonics. A novel class of luminescent materials with intriguing photo-sensitive
capabilities is developing biopolymers loaded with organic dyes (Kawabe and Kato
2012).
3.2.3 Polypeptides
Recently, proteins from many different sources have been extensively studied as
potentially biodegradable polymers due to their dramatically unique physical, chemical, and biological features. Using approaches from self-assembled biodegradable
materials and biochemical technology, polypeptide-based materials are deeply
investigated. Recent studies address the basic concepts and applications of
polypeptide-based biodegradable polymers, as well as the current state of the field’s
bioresearch and potential future approaches. The process of chemical synthesis is
one way of synthesizing peptide-based biodegradable polymers, which can also
include biologically ordered polypeptides such as poly(amino acid) and elastinbased polypeptides, as well as biodegradable polymers with recurring peptide
units. The biopolymers are currently being employed for a wide range of motives,
particularly in the pharmaceutical and food sectors. These include drug delivery
systems, therapeutic targets, anticancer therapeutic agents, protein purification,
injectable scaffolds bio-gels, and tissue engineering applications. Improved uses
are also being investigated at the same time. While, in comparison to other synthetic
materials, polypeptide-based biopolymers have several advantages and drawbacks.
These consist of:
• The drawback of having few structura l components.
• The directed and self-assembled polypeptide-based biopolymers as suitable
approaches, which have drawn a lot of research attention for the development
of therapeutic biomaterials; and.
• The i
ncapacity t
o use them as platforms for tissue engineering bio-based materials
and drug delivery systems owing to their rapid biodegradation in the circulatory
system (Nasrollahzadeh et al. 2021).
Two comm
on methods used to design polypeptides are the recombinant DNA
approach and stepwise solid-phase polypeptide fabrication. Recombinant DNA
technological advances: this technique generates specific polypeptides by modifying
DNA materials. Researchers can introduce genes containing codes for certain
polypeptides into host living things, such fungi, or bacterial cells, and use them as
manufacturers for synthesizing proteins. Finding the genetic material that codes for
the required polypeptide and introducing it into a vector, is the first step in the
procedure. After being inserted into the host’s cell, the viral genome replicates
alongside the DNA of the living body. Upon growth and division, the environment
that supports the species generates the essential polypeptide. The chemical method
62 A. Durmaz et al.
of stepwise solid-phase polypeptide synthesis (SPPS) entails constructing the polypeptide one amino acid at a time, beginning at the C-terminus, and working your
way up to the N-terminus. Usually, SPPS attaches the initial amino acid to a stable
polymer or resin.
3.3 Chemically Synthesized Biodegradable Polymers
Biodegradable polymers can be produced using various methods. For example, they
can be synthesized through fermentation, extraction, bulk synthesis of biopolymers,
as well as endo- and exo-biopolymer product ion. Chemical synthesis o f monomer
units, which can be broken down by enzymes, microorganisms, or biomass, is an
additional production technique. The following is an overview of some widely used
methods to produce biodegradable polymers from both synthetic and organic
materials.
For tissue engineering applications, Ragothaman et al. developed porous 3D
scaffolds by combining collagen and poly(dialdehyde)guar gum and adding a
growth agent (Ragothaman et al. 2014). The sodium periodate technique was
utilized to produce biopolymer blends. These scaffolds included hybrids of covalently linked collagen-based biopolymer blends, in which collagen-based biopolymer blends were necessary for bonding biopolymers by creating imine groups and
stabilizing collagen. Up to 13 days of continuous biopolymer blends relea se from the
scaffolds has been found in in vitro tests. Moreover, the 3D hybrid scaffolds showed
impressive proliferation of fibroblast cell populations, highlighting the capacity to
facilitate tissue regeneration and recovery. In another study, Wang et al. investigated
the effect of porcine fibrinogen biopolymers wound dressing and poly(l-lactide-cocaprolactone) on a preclinical animal wound model (Ragothaman et al. 2014).
rding
Acco
wound microenvironment, re-epithelialization, the development of mature arteries,
and supporting dermal repair. In addition, the external governance of biopolymers
patch exhibited exceptional performance to encourage wound healing independent
of the wound’s diabetic or physiological state. According to this, there is a lot of
opportunity for biopolymers dressing as a therapeutic tool that can help in the
healing of woun ds. In 2023, Zheng and colleagues prepared a new film consisting
of xanthan gum, flaxseed gum, carboxymethyl cellulose, and polygonatum
cyrtonema extracts. Because polyphenols, flavonoids, and polysaccharides, are
included in extracts, adding them reduced light absorption while improving UV
block efficiency, antioxidant capacity, mechanical properties (Zheng et al. 2023).
to their studies, biopolymers significantly altered the diabetes-related
3.3.1 Extraction Methods of Biodegradable Polymers
The selection of appropriate solvents and the design of green processes are of
paramount importance for the benefit of the environment and future generations.
Consequently, the use of solvents in the production of green and sustainable
3 Strategies in Synthesis of Biodegradable Polymers 63
polymers derived from renewable sources will be pivotal in processing industries as
the ‘solvents of the future’. Nowadays, it’s common knowledge that new solvent
structures, often known as “neoteric solvents,” are environmentally friendly methods
of digesting biomass and producing novel advanced materials. Green solvent
systems provide an alternative for dissolving and processing biopolymers, even
though they tend to dissolve in water-based solutions and tre
cals. The ionic liquids and deep eutectic solvents are two of the few green
chemi
ated with a variety of
solvent types that are gaining popularity as alternate solvent options for processing
and dissolving various biopolymers. These solvent systems have several special
qualities, including low vapour pressure, low volatility, thermal resistance, high
recycling capacity, high selectivity, high biodegradability, and more (Prasad and
2019)
Sharma
.
Especially in biomedical studies and technology, chitin-based materials are one of
the most attractive abundant polysaccharide polymers for creating structures with
sophisticated capability due to their distinctive characteristics. Owing to their biodegradable and biocompatible characteristics, they have a wide range of uses in
biomedical and therapeutics. Chitin can make up to 30% of the number of crustacean
shells produced by the seafood industry. This is a significant source of waste that
comes with a high cost of pollution. Chitin is primarily extracted chemical method
from shrimp shells on a commercial basis. Chitin is a polysaccharide derived from
N-acetyl-D-glucosamine groups that is mostly found in shrimp shells, insect species,
and microbes including algaes, fungus, and yeast cells. It is the second most
abundant biopolymer on Earth after cellulose. Demineralization in an acid medium
(such as HCl) and deproteinization in a basic medium (such as NaOH) are the two
steps in the extraction of chitin. On the other hand, acidic mediums (e.g., HNO₃,
H₂SO₄, CH₃COOH, CH₂O₂) can cause the deproteinization process. Usually, indus-
trial extraction uses NaOH. The method of deacetylation into chitosan usually uses
alkaline solutions at high temperatures. Organic solvents may be utilized for decolorization. Although practical, commercial chemical techniques have drawbacks for
the environment and product performance, such as reduced viscosity and molecular
weight. The lengthy nature of the procedure calls for the development of more
effective techniques. Due to its ability to reduce response times, boost yields, and
conserve energy, microwave irradiation has become a more effective heating technique than traditional techniques. Chemical modifications that take hours can be
performed in a matter of minutes by using microwave radiation for threed
sional heating. Numerous studies have exhibited the beneficial effects of
imen
microwave irradiation in several phases of chitin extraction, such as deacetylation,
demineralization, and deproteinization. Microwave-assisted extraction takes much
less time—typically 20–30 min—than traditional procedures and provides greater
quantities and higher degrees of deacetylation. This makes industrial-scale microwave extraction financially viable. The molecular weight, degree of deacetylation,
and crystallinity of chitin and chitosan can all be affected by microwave irradiation,
which may influence their practical characteristics like dissolution, viscosity, and
durability. As a result, careful adjustment of the conditions of extraction is essential
to guarantee the preservation of the intended properties. These days,
64 A. Durmaz et al.
ultrasonic-assisted extraction is ano ther cutting-edge technique that is widely
employed due to its advantages, which include decreased extraction times, economic
benefits, lower consumption of energy, and increased extraction productivity. Typically, high-intensity ultrasound is the basis of the ultrasonic technology process,
which speeds up the extraction of solid substance from a liquid solvent by creating
cavitations in the liquid solution. The studies
that ultrasoni
cation is a viable and alternative method of extracting chitosan with
that have been provided make it clear
high yields. Up to 50 kHz, ultrasonic radiation was used in conjunction with
capacities ranging from 50 W to 400 W. As a result, ultrasonic irradiation proved
to be an effective method for chitin deacetylation, requiring less reaction time than
the traditional procedure and consuming less energy. Overall, research is needed to
the i
completely understand
es
attribut
of the extracted components, as well as to optimize the extraction
mpacts of ultrasonic extraction o n the qualities and
conditions, even if this technology has shown itself to be a feasible one for chitin
and chitosan extraction. The advancement of effective and sustainable extraction
techniques is crucial for the further acceptance and integration of chitin and chitosan
across diverse sectors. The use of bacteria and proteolytic enzymes in biologica
techniques
has become more popular since it is more secure, fewer resources and
solvent-free, and more sustainable. Proteases such as papain, alcalase, pancreatin,
pepsin, trypsin, and devolvase, are among the proteases that can be employed by
enzyme-based extraction to deprot einize a variety of invertebrate shells, such as
shrimp, crab, acetes shrimp, mealworms, and squid gladius. In summary, different
methods are used to extract chitin and chitosan, each with i
ts o
wn benefi
ts
and
applications. Chemical extraction typically involves the use of bases, acids, or
organic solvents to perform demineralization, deproteinization, decolo rization, and
deacetylation. Ultrasonic-assisted extraction utilizes high-intensity ultrasonic waves
to expedite the extraction process, while microwave-assisted extraction employs
microwave energy for quicker and more effective procedures. Biological extraction
ti
utilizes proteoly
safe
and
option compared to chemical techniques. These methods are essential for
c enzymes and bacteria, providing a more environmentally friendly
extracting chitin and chitosan, facilitating their integration into various industries
while considering performance and sustainability factors (Ben Aoun et al.
2024).
l
3.3.2 Polymerization of Biodegradable Polymers
Biodegradable polymers termed biopolymers are present in living things. A biodegradable polymer has a long chain molecule composed of monomers joined by
covalent bonds to form a molecule that is biodegradable. Biopolymers primarily
originate from organic materials such as bacteria, plants, and trees. Compared to
biopolymers, which are intricate molecules with clearly defined three-dimensional
structures, synthetic polymers are more random and simpler. Small molecules
known monomers—the majority of which are organic—may unite with other
monomers to form polymer compounds, which are larger molecules in size. All
monomers can form chemical links with two or more additional subunits. Synthetic
3 Strategies in Synthesis of Biodegradable Polymers 65
compounds called polymers are composed of multiple smaller units known as
monomers. Biopolymers compounds contain chains with an arbitrary number of
monomer units. Polymerization, a chemical process, creates biopolymers by combining many monomer units together. Biopolymers with a linear or branching
morphology can be produced by the polymerization process. Biodegradable
polymers may also resemble a complex, three-dimensional network. Biopolymers,
clu
which in
tion
de proteins (polymerization of amino acids), nucleic acids (polymeriza-
of
tides), and polysaccharides (polymerization of sugars), are biological
nucleo
macromolecules created through the polymerization of monomeric units. A
sequence of distinct reactions that match to the activities of the reacting substances
and their steric impacts come after the polymerization stage.
The commonly used poly(lactic acid) (PLA), a linear aliphatic polyester, holds
great promise for global sustainable development. PLA is derived from a thermoplastic monomer and possesses superior properties. For example, it offers high
strength, chemically inert, low heat distortion temperature, low melting point, low
thermal resistance, poor toughness, high hydrophobicity, low rate of crystallization,
and excellent layer adhesi on. The largest amount of PLA synthesized today
originates from the polymerization of lactide, which is formed from lactic acid
through ring-opening. The ability to produce high quality lactic acid serves as the
foundation for the development of PLA bioplastics. Furthermore, lactide, a crucial
intermediate for PLA fabrication, has a significant influence on the entire PLA
commercial network. Ring-opening polymerization and polycondensation have
been utilized in PLA fabrication thus far. Azeotropic dehydration, Direct polycondensation, second order melt polycondensation, and third-order solid phase polycondensation processes are all included in polymerization. Under comparable
circumstances, ring-opening polymerization usually produces PLA with a high
molecular weight than polycondensation. The dominance of ring-opening polymerization may be challenged to some extent by recent developments in azeotropic
dehydration, second-order melt polycondensation, and third order solid phase polycondensation approaches, which have demonstrated the ability to generate high
molecular weight polymers. Nevertheless, the most efficient method for producing
high molecular weight PLA on a wide scale is still ring-opening polymerization of
lactide (Yu et al.
2023).
3.3.3 Fermentation Method of Biodegradable Polymers
Nevertheless, the significant energy requirements of these two procedures will
further increase manufacturing expenses. Recently, scientists have been focusing
more on the search for innovative, sustainable extraction and filtration methods.
From this perspective, additional studies are needed to determine the ideal recovery
approach that will be least expensive, most efficient, and have minimal adverse
impacts on the environment when applied in a commercial setting. This includes
exploring the use of safe surfactants, green solvents, ultrasound-based extraction,
and floating air dissolved methods.
66 A. Durmaz et al.
Anaerobic metabolism is utilized to generate renewable energy, such as natural
gas and bio-hydrogen, while aerobic fermentation has primarily been used to
produce biopolymers. Researchers have reported a variety of microorganisms in
their experimental studies, including recombinant Bacillus species (spp.),
Escherichia coli (E. coli), Pseudomonas species (spp.), Alcaligenes species (spp.),
Nocardia species (spp.), methylotrophs, Rhizobium species (spp.), and Azotobacter
species (spp.) (Yadav et al. 2023).
Microbial biodegradable polymers are biopolymers formed through fermentation
using microorganisms that have certain sources of nitrogen, carbon, mineral
substances, and salts. These microbial biopolymers are produced mostly because
of their defence system or storage component. Generally, fermentation is used by
microbes, fungi, and algal to generate biopolymers. For instance, Bacillus
sp. produces polyhydroxyalkanoates (PHAs), whereas Xanthomonas campestris
produces xanthan gum. For the purpose of producing biopolymers, various
biological reactors can be constructed for both experimental and continuous fermentation procedures. The solvent composition, product yield, waste management
strategy, and manufacturing expenses should all be thoroughly assessed before
commencing operations. The primary factor adversely impacting the overall finances
of large-scale polymer fabrication is the cost of raw materials. Consequently, several
low-cost carbon sources are typically utilized, including syrup, milk protein, glucose, active sludge, and maple syrup. To produce bacteria biomass in the fermenter,
a great deal of these sources must first be examined, prepared, or evaluated which
raises the prior expenses for polymer synthesis. The downstream stage is crucial and
significantly affects the total cost of synthesis. The recovery of biopolymers from
bacterial culture is now accomplished mostly using solvent-based extraction
approaches; nevertheless, the use of these halogenated solutions compromises the
preservation of the environment. Two important processes in the solvent extraction
and chemical decomposition method that result in pure biopolymers are sedimentation and filtration (Das et al. 2023).
3.3.4 Sonosynthesis of Biodegradable Polymers
An increasing amount of research endeavors have concentrated on the sonochemical
approach because of its many applications in recent years. Because it does not harm
the natural environment, ultrasonic cavitation is extremely valuable in producing
novel biopolymers, especially when it comes to changing naturally formed biodegradable polymers. According to examinations, ultrasonic effect is consistent with
modern techniques of biomaterial preparation since it improves the mechanical
characteristics, morphological properties, agglomeration, and crystal structure of
materials (Cai et al. 2022).
Ultrasonic waves, with frequencies ranging between 2 × 10
categorized as a type of mechanical wave. The development of bio-based materials
aided by sound is linked to the sonosynthesis approach, which is the chemical
consequence of the phenomenon known as acoustic/ultrasonic cavitation. When
4
and 107 Hz, are
3 Strategies in Synthesis of Biodegradable Polymers 67
Fig. 3.1 Sonosynthesis of biopolymer agents
sufficient acoustic waves pass through a liquid, bubbles begin to form, expand, and
quickly collapse a process known as sonochemical synthesis. In Fig.
sonosynthes
is of biopolymers are presented. Up to 5000 K of temperature and
3.1, the
1000 atm of pressure are produced by the combined mechanical power of the
acoustic bubbles before they collapse, transforming into heat as well as additional
types of energy. The heat produced by the high temperatures and high pressure in the
region is sufficient to break all bonds between molecules and form many free
e u
radicals, which are then used to interconnect biodegradable polymers that ar
chemi
The
cal reaction is divided into primary sonochemical reaction, and secondary
seful.
sonochemical reaction categories based on the reaction processes involved. Secondary sonochemical reaction originates when radical species spread into the aqueous
solution from the acustic air pockets, whereas primary sonochemical reaction is
based on the sono-reaction started by the molecules of gases inside the collapse of
acoustic bubbles. There are numerous varia
bles t
hat infl
uence
the synthesis of
biopolymers, including surface tension, sonochemical frequency, acoustic power,
sonochemical time, viscosity, probe types, solvent volume, and the type of free
radicals. Cavitation significantly impacts the yield in sonochemical processes. A
two-phase system can generally be effectively sonicated at the interfaces to prepare
biopolymers such as bovine serum albumin, chitosan, xanthan gum, egg white
protein, gum acacia, lyso
this sono-p
rocess operates at frequencies of about 20 kHz, with durations of between
30 s and 5 min and power densities of between 23 W/cm
zyme, sodium alginate, and starch, among others. Usually,
2
and 500 W/cm2 . In the
aqueous medium, it consists of proteins, polysaccharides, or their bio-composites to
68 A. Durmaz et al.
Fig. 3.2 Drug delivery systems of drug-loaded biopolymer nanocarriers for cancer therapy
form biopolymeric formations; in the oil medium, it contains hydrophobic bioactive
components. The sonochemically manufactured aqueous core-shell biopolymer
based nanocapsules that are in great demand, especially in clinical settings where
they are used for producing cross-linked water/oil (W/O) formulations. The ideal pH
must be reached for each carbohydrate and protein mixture to achieve a negative
charge during the W/O synthesis process. This is a crucial ph
reduce the
electrostatic interaction that forms after mixing these biopoly mer-based
ase since it helps to
mixtures. The blend of biopolymeric solutions comprising hydrophilic bioactive and
oil components is subjected to sonication under specific conditions in the next phase
of producing W/O emulsions. The outcome of the filtration procedure is a liquid
cross-linked encapsulated bio-based structure. Generally, core-shell biopolymer
composites or nanocarriers a
interactions
and exhibit redox/pH sensitive properties. The drug delivery
re formed through covalent bonds and electrostatic
mechanisms of drug-loaded biopolymer nanocarriers intended for cancer treatment
are illustrated in Fig.
efficient
drug release in the cellular environment and gastrointestinal tract in drug
3.2. These extraordinary properties ensure effective and highly
release studies, thus facilitating controlled release. In the light of this information, it
becomes clear that double-effect structures resulting from the combination of
pH-sensitive strategies with a simple and environmentally friendly sonochemistry
es c
method can be produced and multifunctional biopolymer composit
t
importan
role in smart redox/pH sensitive drug delivery systems (Tan et al. 2022).
an play an
While sonochemical synthesis is an attractive method for creating a wide range of
structures, the delivery of biomass-derived chemicals using this approach has only
3 Strategies in Synthesis of Biodegradable Polymers 69
recently gained attention. Previous studies have addressed the primary types of
cross-linked biopolymer agents available on the market for biomedical applications,
including aqueous core-shell nanocarriers, surface-modified biopolymer composites
or blends, biopolymer composites or blends, cross-linked biopolymer composites or
blends, and aqueous core-shell-shell nano/microcapsules.
In summary, the sonosynthesis process of manufacturing these vehicles largely
relies on the chemical changes that occur during ultrasonic cavitation, initiating the
cross-linking of biopolymers at liquid interfaces. Within ultrasonic cavitation, various polysaccharides and p roteins can bind together. Resultantly, the modified
vehicles exhibit high encapsulation performance, robust tolerance to environmental
stresses, and pH-responsive release characteristics.
3.3.5 Solvent Casting Method of Biodegradable Polymers
The main advantages of the solvent casting process over other processes such as spin
coating, microfluidic spinning, salt leaching, and three-dimensional printing are its
low cost, ease of usage, and ability to create robust biofilms with superior physical
characteristics and uniformity. External factors, however, can also cause significant
differences in the features of the components created by the solvent casting
technique between production batches, which might impede manufacture
2023).
(Borbolla-Jiménez et al.
biodegradable polymers films depends on addressing the difficulty of maintaining a
sterile environment during the whole production process in biomedical applications.
The quantity of standardized commercial products is noticeably lacking, despite the
method’s great promise for clinical use and industrial scalability in the development
of biodegradable polymers or composites (Anbuka rasu et al. 2015
frequently employed and popular ways of manufacturing biodegradable mat erials
based on polysaccharides is solvent casting. In order to develop environmentally
friendly polymers, firms have additional ly adopted electrospinning method, layerby-layer assembled method, phase immersion method, injection molding method
and extrusion method, as polymer synthesis methods. A more attractive approach to
developing biopolymer-based films with extremely high quality parameters is solvent casting. The biopolymer was properly mixed into the solution; following the
homogenization process the highly viscous solution should have a small amount of
solid material; and the film should form and be simply removed from the casting
support. These were the primary principles of this synthesis process. The solvent
casting method has higher transparency, more uniform thickness dispersion, and
higher quality compared to extrusion. Nevertheless, this method has more
drawbacks than benefits. These include the need for a lengthy drying period, film
shrinkage after drying, low fracture resistance, uneven distribution of drugs, and
various unfavorable storage conditions. A disadvantage of this method is the “rippling effect,” which causes the film’s shear stress to become problematic and ends up
resulting in a lack of uniformity. Nucleate boiling, a different term for bubble
creation, can occasionally be attributed to over-drying. Plasticizing agents can be
The achievement of the objectives of manufacturing
).
One of the most
70 A. Durmaz et al.
added in conformity with the polymer mixture in order in order to alleviate these
limitations. This will decrease the cohesion intermolecular tensi on within the
polymers, which leads to decreased tension strength and increased elasticity over
the films (Das Adhikary
2023).
3.3.6 Electrospinning Method
The research on the use of bioresorbable cardiovascular implants has been
stimulated, in part, by the current rise in fascination with electrospinning. One of
its primary attractions is the fact that electrospinning is a straightforward technique
requiring minimal professional supplies. An ordinary electrospinning apparatus
typically consists of a spinneret, needle pump, grounded target, and high voltage
power source usually an instrument with a blunt tip needle. The method itself is
effectively conducted out in an experimental setting and may be readily scaled up for
production on a large scale with little changes. To put it briefly, a biopolymer
solution is electrically charged with a high voltage, often several kilovolts, and
carried into the spinneret. To produce a static electric field, a grounded target is set
up at a specific distance away from the charged polymer solution. At the extremity of
the spinneret, a fine jet of entangled polymer networks is pulled out when the surface
tension is overcome by the electrostatic repulsion of the biopolymers, reaching a
critical point when the electrical potential achieves a critical importance. The solvent
in the biomaterial evaporates as this jet hurtles through the air in the direction of the
grounded target, forming a dry bio-based fiber. Depending on how the biopolymer
mixture or solvent is treated, the electrospinning method will produce fibers with a
diameter ranging from 50 nm to 10 μm that are gathered on the grounded target (Sell
2009).
et al.
oxide biodegradable polymers-based nanofibers with curcumin (Gutierrez-Gonzalez
et al. 2020
greatly improved by crosslinking with trifluoroacetic acid and curcumin, with the
latter method significantly exceeding the benefits of the former. They also found that
electrospinning at high humidity levels did not require a regulated environment
when a spinning drum was employed. Wit h an emphasis on protein delivery uses,
Rafiei et al. developed 3D fibrous biodeg radable polymers-based scaffolds composed
2020).
ated by wet electrospinning; it has a greater porosity and hydrophilic properties than
traditional two-dimensional (2D) biodegradable biopolymer mats. Proteins could be
efficiently loaded into the fiber core thanks to this biodegradable structure design,
which also provided controlled release properties that were better than those
achieved through blended electrospinning approaches. Cell cytotoxicity tests were
used to evaluate the biodegradable polymers-based scaffold’s biological compatibility and determine its suitability for a range of biomedical uses. Overall, the 3D
fibrous biodegradable polymers-based scaffold that was created showed potential as
an adaptable structure for tissue engineering and regenerative drug applications
In 2020, Gutierrez-Gonzalez et al. manufactured alginate/polyethylene
).
The mecha nical characteristics of the nanofibers were shown to be
of polycaprolactone (PCL) by coaxial electrospinning method (Rafiei et al.
A scaffold containing biodegradable core-shell fibers was successfully cre-