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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5542_Библиотеки_им_академика_М_И_Перельмана-1.pdf
CHAPTER 5
Plant Macromolecules as Biomaterials
CONTENTS
5.1. Introduction .................................................................................... 138
5.2. Plant Polysaccharides .....................................................................141
5.3. Plant Macromolecules as Biomaterials for Wound Healing ............. 144
5.4. Plant-Derived Compounds .............................................................. 146
5.5. Carbohydrates .................................................................................148
5.6. Proteins .......................................................................................... 152
5.7. Recent Advances Using Plant Biomaterials for Wound Healing ....... 163
5.8. Conclusion ..................................................................................... 165
References ............................................................................................. 167
Introduction to the Study of Macromolecules
138
Skin is the body’s biggest organ, with a reasonably strong arrangement that
serves as a natural screen against physical, chemical, and bacterial harm.
When this pattern is disrupted by acute lesions, the skin goes through a
remarkable healing process that results in wound closure and the formation
of scars.
To maintain the normal control of the skin, this complicated system
relies on various cell types and mediators interacting. In instances such as
diabetes or vascular lesions, faulty skin frequently persists, causing loss of
integrity and, in certain cases, overlaying of structural layers, as well as
delayed skin tissue healing.
5.1. INTRODUCTION
The large molecular weight of plant macromolecules distinguishes them
from all other components. This can range from 10,000 to over 1,000,000,
although the molecular weight of other plant metabolites is rarely greater
than 1,000. Chemically, macromolecules are lengthy chains of tiny structural
units or ‘building blocks that are covalently bonded in a variety of ways.
In the first instance, chemical characterization is dependent on detecting
these smaller components. Proteins, for example, are long chains of amino
acids (up to twenty distinct types) connected by peptide (-CO-NH-)
connections. Polysaccharides are formed similarly by the union of simple
sugar units, such as glucose, linked by ether (-0- ) linkages.
Nucleic acids, on the other hand, are more complicated, with three
structural units: purine and pyrimidine bases, pentose sugars, and phosphate
groups. Proteins, polysaccharides, and nucleic acids are therefore the
three major groups of macromolecules present in plants. However, mixed
polymers, such as glycoproteins, which include both sugars and amino acids
in covalent connection, are also known.
While the polymers listed above all have an ordered structure,
plants contain random polymers generated by oxidative, non-enzymatic
polymerization of simple phenolic components. There are three types of
these: lignins, which are generated from phenylpropanoid units, condensed
tannins, which are derived from flavonoid units, and plant melanins produced
from catechol polymerization.
Thus, DNA and RNA play roles in the storage and transcription of
genetic information, proteins serve as catalysts in enzymatic activities,
polysaccharides serve as a kind of energy storage, and so on. However,
Plant Macromolecules as Biomaterials
139
several plant macromolecules have a specialized role connected to plant
development.
For example, the production of lignin, a polymer that, in conjunction
with cellulose, creates a complex matrix in the cell wall, allows the plant to
build a solid stem or trunk. Plant macromolecule separation and identification
methods differ from those used for low molecular weight components in
several ways.
Solubilizing polymers, for example, is frequently challenging, and
additional techniques may be required. In a simple scenario, macromolecular
components can be dissolved by homogenizing plant tissue with salt solution
and subsequently precipitated by adjusting the extract’s pH.
Because the concentration of various macromolecules (especially
nucleic acids) in plant tissues is low in general, it may be useful to break
the plant cells and separate the different organelles by centrifugation prior
to isolation. The mitochondrial fraction will be high in enzymic protein,
whereas the nuclear fraction will be high in nucleic acid.
Because of the structural complexity of macromolecules in live cells,
any method of separation will almost always result in some degradation
or artifact production unless particular care is followed. Enzymic protein
is particularly prone to breakdown and loss of function during isolation
techniques, therefore it is critical to prevent pH and temperature extremes.
Again, due to their strong relationship with carbohydrates, lignins are
difficul to get pure. The study of macromolecules, whether from plant or
animal tissues, is crucial to understanding molecular biology, and much has
been published about the methodologies necessary for their characterization
elsewhere.
There are also numerous thorough texts on the methods of separating
proteins and nucleic acids, primarily from animal tissue but also from plant
tissue. It will be impossible to address every facet of this large subject in the
space given here.
This description will focus on the difficultie connected with isolating
macromolecules from plant tissues rather than animal tissues. Plant polymer
comparative features will also be examined in depth.
Human bodily tissues have a variety of physical properties, including
stiffness and porosity. Tissue engineering has benefited greatly from a
multidisciplinary interface across topics such as cell biology, biotechnology,
mechanics, materials science, bioengineering, and clinical research.
Introduction to the Study of Macromolecules
140
Many wound dressings have been designed with the goal of restoring
and improving tissue function by creating new biocompatible replacements
or repairing these tissues. However, these materials are relatively expensive,
which may limit their broad usage.
According to this viewpoint, an ideal wound dressing would preserve a
microenvironment in the wounded bed and would direct particular healing
characteristics for each type of wound or illness that affects the patient being
treated.
The wrapping also should maintain hydration levels, which acts as a
barrier against infections and provides thermal insulation for the wound.
As a result, recent biomedical technology investments in the formation of
scaffolds capable of mimicking the natural environment for skin growth and
regeneration after injury.
Polysaccharide-based biomaterials are making a name for themselves
in the field of tissue engineering, primarily as hydrogels for the successful
treatment of wounds and skin burns. They are classified as neutral (glucans,
dextran, and cellulose, for example), acids (hyaluronic acid), basic (chitosan),
or sulfated polysaccharides (heparin and chondroitin).
Chitosan, hyaluronic acid, and alginate are the most common and naturally
occurring polysaccharide-derived biomaterials. These polysaccharides are
further classified as homopolysaccharides (glucans, cellulose, dextran,
and chitosan) and heteropolysaccharides (alginates, agarose, carrageenan,
pectin, galactomannans, and xyloglucans).
All have unique physicochemical features as well as high biocompatibility
and biodegradability, making them useful in biomedical domains. We are
particularly interested in plant macromolecules such as carbohydrates and
proteins (particularly hemicelluloses and lectins) as biomolecules for wound
healing.
Carbohydrates are perhaps the most numerous and significant
biomacromolecules in Nature. Carbohydrates, with the exception of energyrelated molecules, may be separated into two categories: carbohydrates as
matter and carbohydrates as information.
Carbohydrates are plentiful as materials in the extracellular matrix of
mammals and cell walls of diverse plants, bacteria, fungi, and other organisms,
acting as scaffolds. Some common polysaccharides are characterized as
biocompatible materials with adjustable stiffness and functionality, resulting
in polymeric biomaterials that are widely employed in drug delivery, tissue
Plant Macromolecules as Biomaterials
141
engineering, and other applications. Carbohydrates are commonly referred
to as glycans in glycoproteins, glycolipids, and proteoglycans that can attach
to proteins or other carbohydrates and thereby mediate cell-cell and cellmatrix interactions.
These glycans might be reduced to synthetic glycopolymers,
glycolipids, and glycoproteins by polymerization, multistep synthesis, or
a semisynthetic method. Carbohydrates’ information role may be proved
not just as targeting reagents, but also as immunological antigens and
adjuvants. These are also covered in this section because they are always
found in a macromolecular composition. In this section, carbohydrate-based
macromolecular biomaterials are summarized since 2010, with an emphasis
on basic knowledge to drive biomaterial rational design.
Natural occurring polysaccharides, naturally generated synthetic
polysaccharides, glycopolymers/glycodendrimers, supramolecular
glycopolymers, and synthetic glycolipids/glycoproteins will be examined in
terms of their resources and chemical structures.
The multiscale structure-function links in numerous significant
application domains, such as delivery systems, tissue engineering, and
immunology, will be discussed in depth. This study will be useful in the
development of carbohydrate-based macromolecular biomaterials and
will help to bridge the gap between carbs as matter and carbohydrates as
information in order to encourage novel biomaterial design in the coming
years.
5.2. PLANT POLYSACCHARIDES
Plant polysaccharides are macromolecule complexes made up of several
similar or distinct monosaccharides linked together by α- or β-glycosidic
linkages. They are found in plants, such as starch, cellulose, and pectin.
Because plant polysaccharides are distributed widely, the molecular
composition and molecular weight of polysaccharides from various species
vary.
Polysaccharides derived from plants have received a great deal of
interest in recent decades due to their substantial bioactivities and suitability
for therapeutic applications. Previous research has also found that plant
polysaccharides are not poisonous and have no negative side effects.
Plant polysaccharides, as an active portion of antihyperglycemic
plants, play an essential role in the treatment of diabetes management.
Introduction to the Study of Macromolecules
142
Tea polysaccharides, Lycium barbarum polysaccharides, maize silk
polysaccharides, Atractylodes polysaccharides, yam polysaccharides, and
other plant polysaccharides have been shown to lower blood sugar levels.
Because most plant polysaccharides are structural elements of cell walls,
the extraction process is determined by the structure of the cell wall. After
pretreatment, tea polysaccharides are extracted using solvent extraction
(water, acidic, or dilute alkaline solution) to remove fat, monosaccharides,
oligosaccharides, alkaloids, and polyphenols.
Recently, novel techniques for extracting tea polysaccharides have been
developed, including freeze-thaw, microwave, ultrasonic, enzymatic, and
high-pressure procedures. Alcohol precipitation, dialysis, ultrafiltration,
resin or DEAE chromatography, Sephadex chromatography, and CTAB
(hexadecyl trimethyl ammonium bromide) precipitation are all recognized
isolation procedures. Tea polysaccharide yield and bioactivity vary according
to the extraction and isolation method utilized.
Many investigations on the extraction and isolation of tea polysaccharides
have been conducted. In one study, green tea crude polysaccharides were
extracted and isolated using three different extraction methods, including
ethanol precipitation, ultra-filtration technology, and CTAB precipitation,
and the compositions and biological activities of the resulting polysaccharides
were studied and compared.
The results revealed that ultrafiltration produced 23.5 percent and
37.1 percent more active polysaccharides than the other two techniques,
correspondingly. Li et al. researched microwave-assisted tea polysaccharide
extraction and determined the best extraction parameters and rate using
orthogonal experiments based on a single factor experiment:
Microwave power 500 W, (W/V) 1:35, extraction temperature 50 °C,
extraction period 5 min, optimum product yield 1.99 mg/g Enzymes were
used in an extraction procedure with ideal circumstances of temperature 100
°C, W/C 1:26.8, ethyl alcohol concentration 90 percent, and product yield
7.86 mg/g. Under these extraction conditions, the yield of tea polysaccharides
was 25.6 percent greater than without enzyme technology.
Our research created a method for extracting components from tea in
an efficien and complete manner utilizing resins. The very same green tea
source yielded three distinct products: tea polysaccharides, tea polyphenols,
and caffeine. The extraction and isolation processes have an impact on the
product’s purity and bioactivity.
Plant Macromolecules as Biomaterials
143
Plant polysaccharides are biodegradable polymers with stable structures,
and various biological, physicochemical, and hydrophilicity/viscosity
qualities that influence the fluid system’s rheological properties. Starch is
a plentiful polysaccharide biopolymer that has potential applications in
medication administration and wound treatments.
The primary components of starch (amylopectin and amylose) can
be physically/chemically modified to be used in medical applications.
Wet electrospinning is a green technology that uses sodium palmitate to
create pure starch-based nanofibers with great water stability at ambient
temperature.
Figure 5.1. Components of Starch.
Source: Image by Wikimedia Commons
The present focus of research is on producing crosslinked electrospun
nanofibers, such as PVA/starch/chitosan nanofibrous mats in wound
dressings. The improved coaxial electrospinning results in a core-shell
starch-hyaluronic acid/polyurethane-based electrospun nanofibers patch
that is biocompatible, biodegradable, confers surface hydrophilicity and
increases mechanical durability.
Nanoscale cellulose fibers are appealing due to their larger surface area
when compared to their microscale counterparts. Many cellulose derivatives,
including carboxymethyl cellulose (CMC), cellulose acetate, -cellulose, and
ethyl cellulose, produce various electrospun nanofibers in wound dressings.
Introduction to the Study of Macromolecules
144
Unlike drug-free -cellulose nanofibers, antibiotic-loaded -cellulose
nanofibers reduce wound size while providing the desired bioactivity.
Electrospun nanofiber scaffolds based on pectin may serve as superior
wound dressings with high antibacterial activity.
They absorb more exudate in less time than electrospun nanofiber
patches based on alginate or chitosan. Polysaccharides from pectin are
complicated compounds with uneven carbohydrate chains. Because of their
mild hydrophilicity, pectins operate as an exudate-absorbing component in
hydro colloidal wound dressings.
Gums, a major polysaccharide group, are a unique source of electrospun
nanofiber biopolymers with many medicinal uses. Electrospun nanofiber
scaffolds including gum Arabic, gum karaya, gum guar, Ajivas gum, and
gum tragacanth, for example, are utilized in medical applications.
5.3. PLANT MACROMOLECULES AS BIOMATERIALS FOR WOUND HEALING
To sustain skin function, wound healing is a crucial, complicated, and highly
coordinated process. A plethora of molecular and cellular processes are
engaged immediately after damage to stop blood loss, remove bacteria and
foreign materials, and recompose wounded tissue.
These biological and physiological stages in wound repair may be
classified as follows: hemostasis, inflammatory response, cell proliferation
and formation of the extracellular matrix (ECM), and the latter period,
known as remodeling. These stages are not mutually exclusive; rather, they
overlap throughout time.
Platelets circulate near the vascular walls in physiological conditions
and are activated when the continuity of the endothelial layer is ruptured and
the underlying subendothelial matrix is exposed, initiating the first stage of
tissue repair, which is characterized by hemostasis and the formation of a
matrix in the wound bed.
This matrix is the consequence of circulating platelet adhesion and
aggregation to the components of the underlying ECM. Extrinsic and intrinsic
coagulation pathways are activated by damaged tissue and aggregated
platelets to stabilize the fibrin platelet clot.
This entire process serves as a framework for the migration and
proliferation of additional wound-healing cells, as well as a reservoir for
cytokines and growth factors. After then, the inflammatory phase begins
Plant Macromolecules as Biomaterials
145
as an innate immune response to enhance the clearance of cellular and
extracellular waste as well as harmful bacteria.
Platelets and leukocytes both produce inflammatory cytokines, creating
a chemotactic gradient that attracts more leukocytes and amplifies the
inflammatory process. Interleukin-1, IL-1, IL-6, IL-8, tumor necrosis factor
(TNF), platelet-derived growth factor (PDGF), and transforming growth
factor- are examples of inflammatory factors.
Clearly, PDGF is critical early in the chemotaxis of neutrophils,
monocytes, smooth muscle cells, and fibroblasts, whereas TGF- increases
macrophage cytokine release and improves chemotaxis of fibroblasts and
smooth muscle cells.
The very first 2–5 days of the leukocyte response are dominated by
neutrophils, with macrophages taking control on the third day. Neutrophils
have three major purposes. To begin, they create free radicals via the
myeloperoxidase pathway to kill bacteria, which is a critical step for healing
since wounds infected with bacteria do not heal correctly.
They also debride the wound by secreting proteolytic enzymes
that break down non-viable tissue, such as serine proteases and matrix
metalloproteinases (MMP-2 and -9). As a result, neutrophils phagocyte
the dead bacteria as well as the residual matrix. When their activities are
accomplished, they normally die and are cleaned by macrophages.
Monocytes start migrating to the wound and eventually develop into
macrophages. In the inflam atory response, they become one of the major
regulatory cells. M1 phenotype macrophages are related to the phagocytic
activity of residual bacteria, sequestration, and synthesis of pro-inflammatory
mediators in the early phases of inflammation.
After this time, M1 transforms into M2, demonstrating the reparative
nature of macrophages. M2 macrophages are engaged in anti-inflammatory
mediator production and tissue cleaning. These cells eliminate dead
neutrophils, inactive host cells, damaged matrix, and foreign debris.
To enhance and resolve inflammation,M2 cells release cytokines, growth
factors, and other mediators such as TGF-, TGF-, basic fibroblast growth
factor (-FGF), PDGF, and vascular endothelial growth factor (VEGF).
Macrophages control the proliferative stage of healing by driving
fibroblasts, keratinocytes, and endothelial cells to differentiate, proliferate,
and migrate, resulting in new ECM deposition, re-epithelialization, and
wound vascularization. The proliferative stage’s purpose is to reduce
Introduction to the Study of Macromolecules
146
the amount of constricted tissue and fibroplasia while also generating a
functional epithelial barrier to activate keratinocytes. TGF-stimulated
fibroblasts develop into myofibroblast rich in alpha-smooth muscle actin
and can multiply pseudopodia in the ECM, connecting fibronectin and
collagen. This occurrence causes wound contraction, which aids in the
healing process by allowing the wound’s margins to approach.
Those cells additionally make ECM molecules (collagen, fibronectin,
glycosaminoglycans, proteoglycans, and hyaluronic acid), which interact
with the cells to regulate migration, growth, and differentiation. The wound
closure, which includes angiogenesis, fibroplasia, and re-epithelialization,
characterizes this stage.
The last stage of wound healing is characterized by the production of scar
tissue and the growth of new epithelium, a process known as remodeling,
which can take a year or longer. The remodeling is aimed at attaining
maximal tensile strength by restructuring.
In ECM degradation and resynthesis, collagen strands expand in diameter
in tandem with intracellular matrix development, whereas hyaluronic acid
and fibronectin break down. The wound’s traction force gradually increases
with collagen deposition, and these fibers can regain around 80% of the
force compared to normal tissue, but the original tissue’s force can never be
restored.
As established, several variables can influence cell connections and
signaling processes throughout the wound healing process, either favorably
or adversely. Plant-derived chemicals are among these variables, and they
can aid the healing process via a variety of methods.
5.4. PLANT-DERIVED COMPOUNDS
Medicinal herbs have long been used as traditional therapy for a variety
of disorders because they include phytochemicals, which are nonnutritive
compounds found in plants that promote tissue regeneration and function as
pro-angiogenic agents for wound healing.
Furthermore, bioactive plant compounds pique scientificand commercial
interest in the synthesis of novel pharmaceuticals. Plants, on the other hand,
provide a source of various macromolecules, including carbohydrates and
proteins, which are widely employed as biomaterials in wound healing
applications.