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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5911_Библиотеки_им_академика_М_И_Перельмана.pdf
162 P. Chandra et al.
Zhang K, Zhao X, Chen X et al (2018) Enhanced therapeutic effects of mesenchymal stem cell-
derived exosomes with an injectable hydrogel for Hindlimb ischemia
treatment. ACS Appl
Mater Interfaces 10(36):30081–30091. https://doi.org/10.1021/acsami.8b08449
Zhang Y, Wu M, Tan D et al (2021) A dissolving and glucose-responsive insulin-releasing
microneedle patch for type 1 diabetes therapy. J Mater Chem B 9(3):648–657. https://doi.org/
10.1039/D0TB02133D
Zhao X, Song W, Liu S et al (2016) Corneal regeneration by utilizing collagen based materials.
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Zhao Y, Wang Z, Zhang Q et al (2018) Accelerated skin wound healing by soy protein isolate–
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doi.org/10.1016/j.ijbiomac.2018.06.195
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Dr. Phool Chandra, M. Pharm. (BU, Jhansi), Ph.D. (AKTU,
Lucknow) is presently working as Professor and Head at the
Teerthanker Mahaveer College of Pharmacy, Faculty of Pharmacy, Teerthanker Mahaveer University, Moradabad, India. He
has more than eighteen years of teaching and research experience.
He is the author of seven books and 21 book chapters with
different publishers of international repute. He has published 9
Indian Patents and more than 100 research and review articles in
National and International Journals. He is also, the editorial member of different Journals of National and International repute. He
has supervised 36 M. Pharm. and seven Ph.D. research scholars
and is supervising three M. Pharm. and seven Ph.D. research
scholars. Dr. Chandra received the Distinguished Scientist
Award (2022) for outstanding and remarkable contribution to
Pharmaceutical Research during the International Conference on
Drug Engineering, SERB, DST, Govt. of India, New Delhi, and
Shobhit University. He is a member of BOS of TMU and other
Universities. Also, He is an alumnus of Jawahar Navodaya
Vidyalaya Unnao and Amethi (UP), India.
6 Proteins as Biocompatible Material for Biomedical Applications 163
Ms. Rashmi Pathak is currently working as an Assistant Professor in the Department of Pharmacy at Invertis University Bareilly.
She secured a silver medal in B. Pharm. at Invertis University,
Bareilly, and a gold medal in M.Pharm. (Pharmacology) at IFTM
University, Moradabad. She possesses 2 years of experience in
academics. She has published 4 research papers, 11 review
articles, 7 book chapters with national and international
publishers, and 1 Patent. She had organized one FDP and One
workshop as an Organizing secretory and Co-convenor,
respectively.
Dr. Neetu Sachan, M.
Pharm. (UPTU, Lucknow), Ph.D.
(IFTMU, Moradabad) is presently working as a Professor at
Maharana Pratap College of Pharmacy, Kanpur, Uttar Pradesh,
India. She has more than seventeen years of teaching and research
experience. She is the author of four books and 17 book chapters
with different publishers of international repute. She has published
6 Indian Patents and more than 80 research and review articles in
national and international journals. Dr. Sachan has supervised
23 M. Pharm. and eight Ph.D. research scholars. Dr. Sachan has
organized two weeks of FDP and four three-day Entrepreneurship
awareness camps sponsored by the National Science & Technology Entrepreneurship Development Board (NSTEDB), Department of Science & Technology (DST), Govt. of India. For her
role in Entrepreneurship awareness, she received an Award of
Excellence (Entrepreneurship) during a national conference sponsored by the National Commission for Women, Govt of India on
“Expanding Women’s Role in Developing Technology: Increas-
ing Productivity, Improving Lives,” New Delhi organized by
Shobhit University, Gangoh in 2020.
Dr Anurag Verma is currently working as a Professor and Principal, at the College of Pharmacy, Teerthankar Mahaveer University, Moradabad, Uttar Pradesh. He completed his M Pharm
(Pharmaceutics) from KLE’s College of Pharmacy in 1999 and
PhD in Pharmaceutical Sciences from Uttar Pradesh Technical
University in 2012. His research supervisors were Prof Jayanta
K Pandit and Prof A K Wahi (Ex-Professor BHU-IT). He has
25 years of teaching experience, 2.5 years of Industrial experience,
and 14 years of research experience. He has published more than
150 research papers in National and International journals of
repute (Elsevier/Wiley/Taylor & Francis/Nature) and supervised
PhD research work of 14 scholars. He has produced
25 Postgraduates and is presently an advisor to 8 PhD scholars.
Ongoing research programs in his lab focus on Cosmetics, Material science (evaluation of polymers/polymer composites for oral
drug delivery applications), and target delivery through
nanoparticles.
Graphene-Based Carbonaceous Materials: A Sustainable Biomaterial for Biomedical Application
Adam Aberra Challa, Nabanita Saha , and Petr Saha
Abstract
Biomaterials interact with biological systems, revolutionizing fields like tissue
engineering, drug delivery, and implant development due to their biocompatibility and structural adaptability. However, concerns about the sustainability of their
synthesis and sourcing drive the search for eco-friendly alternatives. Fortunately,
carbonaceous materials, particularly graphene and its derivatives, have emerged
as promising candidates. Graphene’s one-atom-thick, sp
ture provides high tensile strength, large surface area, stability, and elasticity. Its
derivates share similar extended characteristics. These properties lead to exceptional conductivity, rapid electron transfer, and high adsorption potential, making
graphene valuable in catalysis, energy storage, and material synthesis. In biomedicine, their targeted surface immobilization, efficient drug loading, and high
biocompatibility enhance applications in drug delivery, biosensing, and antimicrobial coatings. Despite the promise of graphene-based materials, challenges
remain regarding their biodegradability and environmental impact. To this effect,
increasing application of sustainable synthesis from organic sources is taking
place, enhancing their value as viable alternatives. They can be synthesized from
plant extracts, agro-residues, and bio/food waste, offering renewable solutions
with high porosity, structural configurability, and surface functionality. This
chapter explores carbonaceous biomaterials in-depth, examining their structure,
functionality, and diverse biomedical applications. Through a co mprehensive
analysis of recent advancements and prospects, the chapter aims to highlight
2
-bonded carbon struc-
7
A. A. Challa · N. Saha (✉) · P. Saha
Centre of Polymer Systems, University Institute, Tomas Bata University in Zlin, Zlin, Czech
Republic
e-mail: nabanita@utb.cz
#
The Author(s), under exclusive license to Springer Nature Switzerland AG 2025
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_7
165
166 A. A. Challa et al.
the pivotal role of graphene-based biomaterials in advancing biomedical research
and catalyzing healthcare innovations.
Keywords
Carbonaceous nanomaterials · Graphene-based biomaterials · Sustainability ·
Drug delivery · Tissue engineering · Biodegradability
Abbreviations
LEDs Light-emitting diodes
rGO Red uced graphene oxide
GO Graphene oxide
GQDs Graphene quantum dots
PLA Polylactic acid
PEG Polyethylene glycol
RB5 Reactive Black 5
7.1 Introduction
Biomaterials are functional materials produced to interact with the biological
systems of the human body. Their interactions could be on the surface (such as
wound dressing materials), inside the body (such as drug carriers), as aids to the
function of organs (such as heart pacemakers), or as supports to the system of the
body that guide cell growth and tissue regeneration (such as dental applications and
scaffolds in tissue engineering). Advanced fabrication techniques have enabled the
precise tailoring of biomaterials at the molecular level, unlocking more opportunities
for customizing their properties to meet specific biomedical needs.
From b
iocomp
biomaterials available today allows for multiple applications, from enhancing the
biocompatibility of implants to promoting tissue regeneration and engineering
complex organoids for dictating disease characteristics and testing drugs. Furthermore, linked with emerging technological advances such as 3D printing, artificial
intelligence, and microfluidics, the world of biomaterials is currently revolutionizing
personalized medicine by enabling the fabrication of patient-specific implants,
organs-on-chips, and wearable biosensors. As biomaterials continue to evolve,
their impact is increasingly advancing medical treatments, diagnostic tools, and
therapeutic interventions.
The need
From 120 billion USD in 2020 to 140 billion USD in 2023 and an expected market
of 432 billion USD in 2032, the global need for biomaterials is high and rising
steadily (Biomaterials Market Size, Share, & Growth Analysis Report 2023).
atible polymers to nanomaterials and bioceramics, the diversity of
for biomaterials is well described by the current market that it holds.
7 Graphene-Based Carbonaceous Materials: A Sustainable Biomaterial… 167
Recently, the metallic biomaterials sector (such as titanium, chromium, nickel,
stainless steel, cobalt, and their alloys) has held the highest value of market share
within the worldwide biomaterials market and the highest usage is for orthopedics
(Biomaterials Market by Type, Application, and Region – Global Forecast to 2029
2024). This list of application areas where the use of biomaterials is rising includes
dental appliances, wound healing, and tissue engineering fields as well.
Since these statistics indicate the usage of a large amount of materials, it is clear
that it would create an impact on the environment and a disbalance in their development route. Aspects of material sourcing, processing techniques, and testing
methods need innovative solutions. Thus, researchers have long been prioritizing
such phenomena and the viable options are ever-evolving.
One of the notable advances toward such solutions is the utilization of carbonbased materials. Wide availability, alternative sourcing options, an array of
techniques of production, and excellent desired properties made such materials
highly favored. Graphene, carbon nanotubes, carbon dots, fullerenes, silicon carbide,
and others show the level at which carbon technology has reached. Their potential in
biomedicine such as wound dressing, targeted drug delivery, bioimaging, antimicrobial coatings, and tissue engineering is promising, prompting continuous research
efforts to fully obtain their potential.
Graphene is a planar carbon allotrope that is built with carbon atoms in a crystal
hexagonal honeycomb structure. It exhibits one of the highest mechanical strengths
(a tensile strength of nearly 130 GPa, and a Young’s modulus of up to 1 TPa) (Zhu
et al. 2010 ) when it comes to building blocks. It can be shaped into distinct
geometrical features. It can be wra pped into a 0-dimension (fullerene), rolled into
a 1-dimension (carbon nanotubes), or stacked into 3-dimensions (graphite).
Graphene-based materials have a lot to offer to the biomedical field given their
properties. For instance, their increased surface area facilitates efficient drug delivery, while their superior mechanical properties bolster developments in tissue
engineering. Additionally, these materials demonstrate notable capabilities for surface immobilization, efficient drug loading, proven antimicrobial properties, and
heightened biocompatibility.
f t
One o
he most important advantages of using carbon-based biomaterials,
including graphene, is the fact that they can be obtained from cheap, alternative,
natural origins. This shines not only on their potential for mass production but also
on the development of improved properties. Using straightforward processes such as
graphitization and pyrolysis for converting these sources to nanomaterials, combined
with innovative graphene synthesis techniques, including epitaxial growth and
chemical vapor deposition, these carbonaceous materials show exceptional
characteristics. Their high porosity, structural configurability, and surface functionality make them highly versatile for multiple purposes.
Within the context of biomedical engineering, however, the persistent challenges
related to the biodegradability of carbonaceous nanomaterials require deeper investigation into their possible environmental impact. Nonetheless, extracting these
materials from organic sources like plant residues and agricultural waste as mentioned above, offers a potential solution, as they are prone to enzymatic degradation.
168 A. A. Challa et al.
This not only addresses concerns regarding their ecological impact but also enhances
their value as sustainable and viable alternatives. This chapter dives deep into the
world of carbonaceous biomaterials where graphene-based materials are centered. It
iterates their exceptional properties and applications in diverse areas by focusing on
biomedicine. The sustainability aspect of biomaterial usage is also well explained in
the sub-sections of this piece.
7.2 Graphene and Its Family
Dubbed “wonder material” graphene is considered one of the most revolutionary
nanomaterials in material science. This is mainly because it boosts superb physical,
mechanical, electrical, and optical characteristics among others. These phenomena
have granted it a preference in the material science world. For instance, its high
mechanical strength is a recipe for a good bone tissue scaffold, whereas its excellent
electrical conductivity makes it capable of being used in neural and heart tissue
engineering (Ghosal et al. 2021). Its surface topography and mechanism make it
suitable for diversified execution. Having an elaborate surface area and the ability to
be functionalized, Graphene is suitable for producing composite materials. The
following sub-sections deal with its structure, properties, and functionalities.
7.2.1 Structure of Graphene
The one-atom-thick hexagonal lattice structure gives graphene its uniqueness. It has
a stable configuration because of the tight packing through the in-plane σ bond
formed by its sp
has a 1s
2 2s2 2p2
three orbitals (s, p
each. Whereas the unhybridized p
plane forming π bonds in either π state (valence band) or an empty π* state
(conduction band) (Samantara et al. 2019). The sp
2
orbital hybridization. Carbon has four valence electrons. Hence it
electron configuration. In graphene, from the four orbital electrons,
, and py) hybridize to form covalent bonds with one carbon atom
x
orbitals interlock with other atoms on a parallel
z
2
covalent bonds give it its
exceptional mechanical properties even higher than that of diamond which has sp
hybridized carbon bonds. Whereas, the π bond which is located perpendicular to the
surface of the lattice, is associated with the electrical conductivity of graphene
(Deretzis and La Magna 2011; Yang et al. 2018).
As c
e seen in the schematic in Fig. 7.1, the cut section of the graphene
an b
structure shows either zigzag or armchair edges. The zigzag edges form what are
known as edge states, which show superior quality in terms of electronic and
magnetic activities (Enoki et al. 2012). Hence, structural configurations are important in defining the usage of graphene.
There are two carbon atoms in every unit cell of a one-layered structure of
graphene. The distance between the two atoms is 1.42 Å (0.142 nm), with a lattice
constant of 2.46 Å (0.246 nm). Such a layer is 0.34 nm thick. Evidently, graphene’s
lattice structure is interpreted as two intertwined triangular sub-lattices, termed A
3
7 Graphene-Based Carbonaceous Materials: A Sustainable Biomaterial… 169
Fig. 7.1 The planar lattice
description of
layer
a graphene
and B, originating from the two atoms found in its unit cell (Avouris and
Dimitrakopoulos
2012).
7.2.2 Properties of Graphene-Based Biomaterials
The structural configuration and unique architecture of graphene are responsible for
the range of capabilities that it has, linking it to the description, “a wonder material”.
Graphene has a thermal conductivity that reaches 3000–5000 W/m.K which puts it
above its close contenders such as copper and diamond. Its electron mobility is
measured as high as 200,000 cm
2
/V.s, indicating the ease with which electrons can
be carried through. In addition, graphene’s optical transparency as a single layer can
be about 97.3% which can be deemed as completely transparent (Moosa and Abed
2021). Graphene is inert, and relatively stable due to its σ bonds, and because it lacks
hydroxide groups on its surface, it has poor water solubility. On top of that, it is
embodied with a large surface area measurement of 2630 m
Other m
rials in the graphene family also encompass exceptional properties.
ate
2
/g.
Graphene oxide, as the name implies, is an oxygen-containing form of graphene
formed through the intercalation and oxidation of graphite. Through its synthesis, it
is equipped with various functional groups such as hydroxyl (C-OH), carboxyl
(C-COOH), carbonyl (C=O), and epoxy (C-O-C) attached to the surface. These
functional groups are found on the basal planes (hydroxyl and epoxy) and edges
(carboxylic) of the GO sheets, where aliphatic regions are formed (Aliyev et al.
2019)
ecause of these functional groups, GO forms stable suspensions in aqueous
. B
or many other solutions.
Reduced graphen
e oxide (rGO) is considered to have a graphene-like behavior
even though it does not match the properties of that of pristine graphene. However, it
is a viable material because of its manageable functionality, and superb electric and
170 A. A. Challa et al.
thermal conductance (Gürsel 2020). In addition, the ease of attaining its precursor
and the scalable synthesis routes make it more attractive among the graphene family.
Valid to applicable areas, rGO shows hydrophobic behavior much like graphene,
because of the lack of oxygen-containing compounds.
Graphene quantum dots (GQDs) are essentially sheets of graphene that are less
than 100 nm in their lateral dimension. They have a monoatomic layered planar
structure, broad surface area, and oxygen-containing functional groups on their
surface which can provide significant active sites for molecules to atta ch (Zhao
et al. 2020). GQDs are mostly soluble or dispersible in water and are biocompatible
with human neural cells. They also possess stable photoluminescence and adjustable
band gap (Smith et al. 2019).
7.2.3 Synthesis of Graphene Compounds
Graphene is synthesized using either top-down or bottom-up processes (Fig. 7.2).
The former includes mechanical exfoliation, electrochemical exfoliation, or reduction of graphene oxide. These processes, although easy and cost-effective, pose
difficulty in managing the quality of the output such as the quantity of the individual
layers of graphene sheets. The latter include organic synthesis, epitaxial growth, or
chemical vapor deposition. These methods result in better quality products but are
expensive to maintain in comparison.
• Mechanical exfoliation was the primary method used for the discovery of
graphene. This is done by peeling off a highly oriented pyrolytic graphite using
scotch tape. The challenge in such exfoliation is the lack of control over having a
desired output. Hence, researchers have been working on optimizing this route to
synthesize single-layer graphene with a significant structural quality (Moosa and
Abed 2021).
• Chemical vapor deposition is a process that utilizes a substrate upon which an
element in a gaseous form is deposited. For a long time, it has stood as a scalable
and economical method for generating high-quality graphene films, making it the
foremost choice for large-scale graphene production (Saeed et al. 2020). This
method is preferred when it comes to graphen e ’ s electronic applications. How-
ever, achieving precise control over the thickness is challenging.
• Electrochemical
exfoliation involves
applying a certain voltage to electrolytes to
chemically release their ions (such as sulfates) and integrate them into the
interlayer of graphite rods to break them into graphene sheets (Achee et al. 2018).
Epitaxial growth of
•
graphene mainly requires a silicon carbide substrate. This
substrate is subjected to a high temperature during which thermal decomposition
of the silicon atoms takes place. This leaves the carbon atoms to diffuse and grow
into and graphene honeycomb lattice (Zebardastan et al. 2023). It is mainly
beneficial to the semiconductor industry as the graphene is directly grown on
the intended substrate.
7 Graphene-Based Carbonaceous Materials: A Sustainable Biomaterial… 171
Fig. 7.2 Process routes of the two synthesis methods of graphene. (Reproduced under the terms of
the CC-BY license (Su and Hu
published by the Society of Chemical Industry and John Wiley & Sons Ltd)
2021) # 2020 The Authors. Energy Science & Engineering
Although graphene’s derivates (GO, rGO, GQDs) could share similar synthesis
routes as graphene itself, they have their dedicated met hods that relate to their
properties.
GO i
n intercalated and oxidized derivative of graphite sheets. The conventional
s a
method to produce GO is the modified Hummer’s method. A carbon source (usually
graphite flakes or powders) is mixed with a protonated solvent (such as sulfuric acid,
phosphoric acid, or a combination of these) and a strong oxidizing agent (potassium
permanganate) is introduced. The solvent will be the intercalating agent and the
latter will induce the formation of the funct ional groups. After diluting with
deionized water, hydrogen peroxide is added to the resulting mixture to remove
any metal ions that remain from the oxidizer. The final product is obtained by
repeated centrifugation and sonication processes.
To synth
esize rGO, chemical, thermal, or electrochemical means can be used as
reducing mechanisms for GO. The following specific methods can be utilized to
obtain rGO (Smith et al. 2019):
172 A. A. Challa et al.
(a) chemical reduction of GO using hydrazine, metal hydrides, or hydrohalic acids
(b) photocatalytic reaction of GO under UV light and the presence of a catalyst
(c) exposure to high-intensity pulsed light produced from xenon flash tubes
(d) heat treatment of GO using urea as an expansion-reduction agent
(e) thermal treatment of GO in a furnace at high temperatures
The chemical reduction of GO involves the use of harmful chemicals and this has
been a cause for concern. Fortunately, there are greener alternatives to solve this
issue and will be discussed in a later sub-section.
GQDs, as quantum derivatives of graphene, are formed through top-down or
bottom-up procedures as well. The top-down method incl udes, for instance, the
exfoliation of carbon into GQDs that are nanosized using methods like electron
beam lithography and liquid exfoliation. Conversely, the bottom-up techniques
include growing molecular components, such as polymers or graphene-like aromatic
hydrocarbons, into GQDs by hydrothermal, microwave-assisted hydrothermal, and
metal-catalyzed methods (Tian et al. 2018).
Graphene is capable of creating composites, as are its derivatives, for various
applications. Graphene and a chosen component can be bonded by covalent or
noncovalent connections through a variety of c hemical processes. Covalent
connections are attained by nucleophilic, cycloaddition, condensation, and electrophilic reactions. Whereas noncovalent connections are made possible through π–π
bonding, electrostatic interactions, hydrogen bonding, and ionic interactions
(Karthik et al. 2021; Kumar et al. 2023). Through these means, graphene can be
functionalized with many polymers, such as chitosan, gelatin, and polyethylene
glycol (PEG), to mention a few.
7.2.4 Applications of Graphene Compounds
The areas of application of graphene and its compounds are vast. They e xhibit
exceptional conductivity, fast electron transfer capabilities, efficient heat transfer,
and adsorption capabilities. As a result, they find widespread application in catalysis
improvement, energy generation and storage enhancement, and material synthesis.
nstance, i
For i
graphene-containing materials attract active metal particles ensuring uniform dispersion. This phenomenon coupled with the large surface area and superb electrical
conductivity, enhances electrochemical reactions such as fuel oxidation and oxygen
reduction reaction (Su and Hu 2021). Such higher activity prompts the immobilization of the typical platinum catalyst used in the anode of the fuel cell and improves its
stability.
The atom
as active materials in electrical components including supercapacitors, electrochemical batteries, and Lithium-ion capacitors (Wang et al. 2019). Their potential in this
field is immense, signaled by their affordability, abundance, diverse allotrope s and
transformations, as well as exceptional physical and chemical stability.
n fuel cells, the many anchoring sites found on the surfaces of
ic-level architecture of graphene and its composites cultivated their use