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Carbon-Based Nanomaterials: An Overview 25
Fig. 8 Biomedical applications of carbon-based nanomaterials

5.5 Biomedical Applications

Carbon-based nanomaterials have emerged as revolutionary entities in the realm of biomedical applications, displaying their versatility and exceptional properties. These materials hold immense promise in various biomedical fields, ranging from drug delivery and imaging to tissue engineering and biosensing. (Fig. 8) The inherent ability of carbon-based nanomaterials to interact at the molecular level opens up new avenues for targeted therapies and diagnostic tools, paving the way for ground­breaking advancements in the field of medicine and healthcare.
5.5.1 Tissue Engineering
The ideal tissue engineering scaffold should provide microenvironment for cells that closely mimics the natural conditions found in the human body’s tissue. CN­based scaffolds offer notable benefits for promoting cell development, demonstrating minimal cytotoxicity, facilitating productive nutrient administration in the scaffold
26 S. K. Swain et al.
microenvironment by featuring chemically modified components conducive to cell– cell communiqué and enhancing cell distribution capability for bone tissue engi­neering. CNTs exhibit an axial Young’s modulus of about 1 TPa and 150 GPa of tensile strength value, attributed to the high stiffness of the hexagonal molecular network formed by the C–C bonds. As a result, CNTs serve as rigid substances with the ability to undergo deformation either due to the impact of electric force or under the influence compression. Modifying the surface of CNTs or functionalizing their surface stands out as an effective approach for improving interactions between cells and scaffolds, consequently enhancing cell spreading within the proximate environment of the scaffold region.
Biological scaffolds based on carbon dots (CDs) have been proposed as potential substances for bone resurgence and the refurbishing of bone imperfections. The find­ings demonstrated that the optimal biological activity, including osteoblastic affixa­tion, osteogenic differentiation and rapid increase in cells development,was achieved with a composite comprising 10% by weight gelatin in polymeric CD-peptide. Fullerene-based scaffolds play a crucial role in diverse bone tissue engineering applications, offering favourable conditions for bone cell proliferation with minimal cytotoxicity. Their unique properties contribute to effective stimulation of bone cell growth.The increased hydrophobicity and surfaceroughness of fullerene-based scaf­folds enhance their capacity to regulate cell attachment, leading to improved bone tissue thickness. This, in turn, facilitates the unique mineralization process associ­ated with CNs. The distinctive structural features of the fullerene molecule allow for precise organization and regulation of the morphology in the final bone tissue structure.
NDs, recognized as the sole non-toxic CNs, have recently found applica­tion in bone tissue engineering. Unlike other carbon nanomaterials, these NDs offer distinct advantages, including commendable mechanical strength, effective osteogenic activity, positive stimulation of mineralization and noteworthy anti­inflammatory properties [111]. Parizek et al. conducted a separate study where they engineered polymers coated with NDs for applications in bone tissue engineering. The study revealed that PLGA-ND exhibited significant mechanical strength and demonstrated the ability to bind with human osteoblast-like MG-63 cells, facili­tating their proliferation. Notably,this technique stands out for its safety, non-toxicity and non-inflammatory characteristics [112].CNshavealsoproveneffectiveinover­coming challenges associated with the regeneration of cartilage and cardiac tissue [113, 114].
5.5.2 Wound Healing
Wound management involves creating a conducive surrounding for the wound to heal without skin deterioration, encompassing considerations such as size, serious­ness, profoundness and region. CNs exhibit unprecedented feasibility in managing
Carbon-Based Nanomaterials: An Overview 27
inveterate wound infections in contrast to conventional avenue. While their biocom­patibility remains a subject of controversy, the robust geometry of CNs equips them to undergo four distinct mechanisms as outlined below:
Crack bridging is a mechanism wherein CNs exert stress to counterbalance
applied forces by spanning the two surfaces, thereby impeding and retarding
crack progression.
In the pull-out mechanism, CNs are recognized for extracting the matrix and
exerting interstice friction, effectively deaccelerating the propagation of cracks.
In the crack deflection mechanism, the crack dissipates great energy as it follows
an intricate route, and the existence of CNs prevents the crack from continuing
along its trajectory.
In crack tip shielding, the apex of a rupture is constrained, resulting in an
insufficient magnitude of energy for the debonding of the interfacial region.
CNs have a direct impact on the morphology, virtue of cell membranes and metabolic pathways of microscopic creatures. The dimension, quantity and exterior part of these CNs contribute to the effective inactivation of microbes. Fullerene stands out as an excellent material for preventing bacterial infections. Fullerene possesses outstanding antioxidant properties, rendering it a promising candidate for applica­tion in wound healing. Its capability to detoxify reactive oxygen/nitrogen species and scavenge them is noteworthy. Additionally, in photodynamic therapy, fullerene can generate reactive oxygen species upon exposure to light. It has been identified as a beneficial agent in enhancing wound healing by actively participating during the modulation of inflammatory and proliferative stages.
Recent studies have highlighted the cell and tissue regeneration-promoting prop­erties of GO. rGO is frequently preferred over GO because of its exceptional elec­trical conductive nature. In vitro and in vivo investigations have reported the accom­plished application of GO and rGO in wound closure and recovery mechanisms, attributed to their astonishing possession. These materials facilitate the relocation and proliferation of keratinocyte cells, thereby promoting the closure and recovery process of wounds. Moreover, GO exhibits angiogenic possessions. These materials can be incorporated into a wound dressing patch for enabling regulated administra­tion and release of active components essential for the process of wound healing. Graphene demonstrates a significant attribute of uniform dispersity upon release, maintaining its antibacterial activities and promoting the migration of human fibrob­lasts. This makes it highly suitable for application in wound dressings. The inves­tigation demonstrated that graphene preserves its bactericidal actions via wrapping methods and sharp-edged when enzymatically released. Graphene and its nanohy­brids exhibit substantial antibiofilm actions and wide range of bactericidal effects. The antimicrobial mechanism of GO includes lipid extraction, chemical oxidative stress, mechanical wrapping and a cutting-edge nanoknife impact. These peculiar­ities collectively contribute to delaying the development of microbial resistance to GO.
CNTs are recognized for enhancing the epithelization process by increasing the wideness of the epithelium in wound recovery process. CNT-based materials
28 S. K. Swain et al.
exhibit a range of properties, including antibacterial, antimicrobial, antioxidant, adhesive and mechanical attributes, which can collectivelycontribute significantly in wound closure and recovery mechanism. An investigation involving human dermal fibroblasts and murine fibroblast cells was conducted to investigate the impact of MWCNTs. The conclusion drawn was that MWCNTs initiate wound healing action by suppressing genes associated with adhesion.
ND exhibits outstanding characteristics with the existence of hydrophilic func­tional groups on its exterior part, enhancing the effective superintendence of moisture and promoting extend of wicking process during wound dressing. The scaffold also demonstrated magnificent cellular performances. It was observed that the agglomer­ation of NDs was influenced by a higher concentration of NDs in nanofibers, leading to enhanced hydrophilic behaviour without exhibiting cytotoxicity.This study estab­lished the antibacterial activity of NDs, revealing that an increment in concentration of NDs resulted in a decreased binding affinity of Staphylococcus aureus bacteria. Cell viability, cytotoxicity and cell proliferation assays were conducted to verify the possessions of NDs in wound closure and repairing pathways. Both in vitro and in vivostudies substantiated that scaffolds fabricated from ND-dispersed nanofibrous are highly favourable for managing intricate and deadly wounds.
CQDs demonstrate outstanding catalytic and fluorescence properties, along with antibacterial capabilities, making them suitable for biomedical applications. However, uncertainties persist regarding the interaction of CQD with bacteria, the predicament of defensiveness and the manifestation of bactericidal actions. In one of latest investigations, the bactericidal possessions of positive charge-carrying CQD were highlighted, indicating their activeimpact on various types of bacteria, including Gram-negative, Gram-positive and drug-resistant strains. Their research gets undi­vided concentration on understanding the mechanism of positive charge-carrying carbon nanodots. The study revealed that –NH
- and –NH-modified carbon nanodots
2
lead to initiate robust adherence action on t he cell membrane of bacteria [115].
5.5.3 Drug Delivery
Although the four distinct classes of carbon materials those differ in their size, dimen­sions and shapes, they all share characteristics of nanoengineered materials with numerous captivating attributes that render them appealing as therapeutic adminis­tration vehicles. Primarily, CNs have the ability to disperse in aqueous media. In addition to straightforward translocation via cellular membranes, CNs also demon­strate the capability to penetrate cells via energy-driven endocytic routes. Secondly, they can penetrate and amass within tumour tissues due to the enhanced permeability and retention (EPR) effect. The EPR effect facilitates the preferential transport of CNs loaded with medication components to tumour locations, enhancing the effec­tiveness of regulated delivery for antitumor therapeutics. Thirdly, CNs demonstrate an exceptional capacity for therapeutic accommodation onto their surface through both covalent and non-chemical associations, attributed to their high aspect ratios and surface areas [116].
Carbon-Based Nanomaterials: An Overview 29
The ability to create supramolecular substances with polycyclic aromatic molecules via π–π stacking is one of the distinctive features of CNTs. The surface of pristine CNTs can adsorb various anticancerous therapeutics as well as huge poly­meric anticancer constituents. The binding forces at play in such interactions involve stacking associations between the water-repulsive parts of the adsorbed molecules and the lipophobic surface of CNT, characterized by π–π stacking associations. As numerous anticancer therapeutics possess water-repulsive properties, these forces play a key role in facilitating the accommodation of such therapeutics onto or into the CNTs. Furthermore, the likelihood of ionic interactions is high, facilitating the adsorption of molecules, particularly in instances where the CNTs surface has undergone chemical modification involving charged functional groups [117].
Due to t he numerous advantages of CDs, including rapid cell extraction, excellent biological compatibility, robust fluorescence, long-lasting stability and no impact on therapeutics actions, many scientists utilize CDs as multipurpose systems for thera­peutic administration and loading. As an illustration, CDs were incorporated into the zeolite imidazole framework (ZIF). This 5-FU therapeutic carrier highlighted pH­sensitivemedication administration. Since 2008, multiple research groups have dedi­cated their efforts to the development of medication administration vehicles crafted from nanographene. Monolayers of GO or rGO can serve as effective platforms for therapeutic loading owing to their enriched specific exterior region. The electrons present on the exterior regions of the nanographene can form bonds with diverse arrays of aromatic therapeutic molecules via π–π associations. Subsequently, the modified GO or rGO surfaces can be connected with targeting molecules, enabling the selective administration of medications to specific cells [118]. Meticulously planned therapeutics those can be loaded onto GO include doxorubicin (DOX) and camptothecin (CPT).
A diverse array of therapeutics or substances can be readily associated with the exterior and interior surfaces of fullerenes because of their peculiar structural features that incorporates sundry conjugated double bonds. This makes them compe­tent substances for clinical applications. However, the hydrophobic characteristics of fullerenes pose a limitation on their pharmaceutical activities. To address this issue, chemical modifications have been carried out using organic components such as amino acids, carboxylic acids, polyhydroxy groups and amphiphilic polymers. Apart from their outstanding chemical and optical possessions, the facile modifica­tions of NDs’ surface render them quintessential suitors for biomedical and phar­maceutical applications. Moreover, over the past few years, numerous studies have provided evidence supporting the biocompatibility and non-toxic nature of NDs. In general, NDs are regarded as the least risky among nanocarbon components. Hence, researchers have extensively explored their potential applications as thera­peutic administration agents, diagnostic equipment and imaging instruments. Further modification is crucial to prevent the aggregation of NDs and enable their use in therapeutic applications, which can be categorized into two distinct classes: one is doping and another one is surface modifications. The doping process resulted with imperfections inside the materials, caused by extraneous atoms through high-energy methodology, subsequently leading to generation of optically active components.
30 S. K. Swain et al.
Surface modifications of NDs involved chemical reactions with organic components, namely, natural polymers, genetic material peptides and amino acids to enhance the biomedical-related activities and possessions of NDs [119].
5.5.4 Sensing
In recent times, CNs have been subjected either to thorough examination, serving as discrete molecular-like sensors or as components that can be seamlessly inte­grated into devices. In addition, the approaches for integrating carbon nanomate­rials into biological sensors encompass direct growth on a substrate, drop casting, integration into polymers, co-deposition with metal nanoparticles and utilization in field-effecttransistor (FET)-based devices to augment conductivity [120]. Graphenes and CNTs exhibit distinctive physicochemical properties, including charge carrier mobility thermal conductivity and specific surface area, which have garnered their attention in biosensing applications. These materials are frequently employed to enhance electrode functionality by providing excellent conductivity, high specific surface area and robust binding affinity for other nanoparticles and probe molecules. This modification aims to achieve heightened sensitivity in immunosensors [121]. Functionalized fullerenes and electrodes modified with fullerenes have proven effec­tive in detecting a diverse array of molecules, such as fluoride ions, glucose, H
2O2
and various organic vapours [122]. CDs have undergone extensive exploration due to their tailored optical possessions, resistance to photobleaching, low noxious effect and remarkable cell-friendly capability. A crucial advantage of CDs stems from the adjustable fluorescence properties, originating from the quantum confinement conse­quences and the surface or edge ramification. The fluorescence emission wavelength of CDs can be modulated across the strong ultraviolet to near-infrared domain by controlling man-made precursors, circumvents and approaches. This versatility posi­tions them as propitious frameworks for applications in biosensing and bioimaging [123]. SWCNHs exhibit the characteristic of self-aggregation, leading to the forma­tion of 80–100 nm spherical conglomerates with diverse morphological structural entities such as dahlia, bud and seed structures, rather than remaining disseminated individually. These distinctive shapes impart unique properties, including great exte­rior surface region, abundant interior nanospace, high conductive value and mechan­ical strength, rendering them best-suited substances for various sensing applications such as electrochemical, fluorescent and resistive sensing. Initially, SWCNHs have found extensive use as electrode materials in electrochemical sensing. Additionally, beyond electrochemical sensing, SWCNHs have been employed in other sensing modalities, such as resistive sensors, capitalizing on the conductive characteristics inherent in SWCNHs [124]. SWCNHs extensively implemented in the biosensing of H
, glucose, etc. [125, 126].
2O2
Carbon-Based Nanomaterials: An Overview 31

6 Challenges and Future Perspectives

Existence of nanostructured carbon-based materials is known since ancient age; however, their properties towards potential application needs to be further elaborated as future prospective materials. The nano-dimensional CNMs havemagic property as compared to their bulk counterparts because of their high aspect ratio. The structure and morphology of CNMs have major role predicting their application in various sectors including diversebiomedical applications. Nowadaysresearchers are engaged to synchronize the properties with application in length and breadth to propose a future prospective smart material.

7 Concluding Remarks

The surface-to-volume ratios of CNMs are very important for exploring different unexpected properties inviting various proposed applications. From graphene’s exceptional conductivity to CNT’s extraordinary strength are the example of the versatility of CNMs. Going deeper into the intricacies of CNMs, not only their impressive physical attributes but also the potential for sustainable solutions and eco-friendly applications of CNMs are uncovered. This chapter has provided a foun­dation for understanding the diverse nature of CNMs, their synthesis methods and the crucial role they play in shaping the future of biomedical application to meet the scope of the present book.
Acknowledgements Authors convey their thanks to the Department of Science and Technology, Government of India, for providing INSPIRE Fellowship to S. Patra for pursuing her PhD degree. The University Grant Commission, New Delhi, India, is also acknowledged for awarding SJSGC doctoral fellowship to K. M. Sahu.
Conflict of Interest The authors declare that there is no conflict of interest in publishing this article.

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