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<journal-id journal-id-type="publisher-id">Front. Bioeng. Biotechnol.</journal-id>
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<journal-title>Frontiers in Bioengineering and Biotechnology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Bioeng. Biotechnol.</abbrev-journal-title>
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<issn pub-type="epub">2296-4185</issn>
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<publisher-name>Frontiers Media S.A.</publisher-name>
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<article-id pub-id-type="publisher-id">1732037</article-id>
<article-id pub-id-type="doi">10.3389/fbioe.2025.1732037</article-id>
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<subject>Review</subject>
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<title-group>
<article-title>Carbon nanotubes for wound healing: material design, mechanistic insights</article-title>
<alt-title alt-title-type="left-running-head">Poddar et al.</alt-title>
<alt-title alt-title-type="right-running-head">
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fbioe.2025.1732037">10.3389/fbioe.2025.1732037</ext-link>
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<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Poddar</surname>
<given-names>Nidhi</given-names>
</name>
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<sup>1</sup>
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<name>
<surname>Naik</surname>
<given-names>Kaustubh</given-names>
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<sup>2</sup>
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<contrib contrib-type="author" corresp="yes">
<name>
<surname>Kumari</surname>
<given-names>Sushma</given-names>
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<sup>1</sup>
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<aff id="aff1">
<label>1</label>
<institution>Centre for Biomaterials, Cellular and Molecular Theranostics, Vellore Institute of Technology</institution>, <city>Vellore</city>, <state>Tamil Nadu</state>, <country country="IN">India</country>
</aff>
<aff id="aff2">
<label>2</label>
<institution>Department of Cell Biology and Physiology, Washington University School of Medicine</institution>, <city>St. Louis</city>, <state>MO</state>, <country country="US">United States</country>
</aff>
<author-notes>
<corresp id="c001">
<label>&#x2a;</label>Correspondence: Kaustubh Naik, <email xlink:href="mailto:knaik@wustl.edu">knaik@wustl.edu</email>; Sushma Kumari, <email xlink:href="mailto:sushma.kumari@vit.ac.in">sushma.kumari@vit.ac.in</email>
</corresp>
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<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2026-01-12">
<day>12</day>
<month>01</month>
<year>2026</year>
</pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2025</year>
</pub-date>
<volume>13</volume>
<elocation-id>1732037</elocation-id>
<history>
<date date-type="received">
<day>25</day>
<month>10</month>
<year>2025</year>
</date>
<date date-type="rev-recd">
<day>09</day>
<month>12</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>17</day>
<month>12</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2026 Poddar, Naik and Kumari.</copyright-statement>
<copyright-year>2026</copyright-year>
<copyright-holder>Poddar, Naik and Kumari</copyright-holder>
<license>
<ali:license_ref start_date="2026-01-12">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p>
</license>
</permissions>
<abstract>
<p>Chronic wounds such as diabetic ulcers remain significantly higher in global healthcare burden due to impaired angiogenesis, infection, and sustained inflammation. Carbon nanotubes (CNTs) are promising candidates for advanced wound-dressing applications due to their exceptional electrical conductivity, high mechanical strength, photothermal performance, and ease of surface modification. This review discusses recent progress in their functions in haemostasis, microbial protection, anti-inflammatory regulation, and tissue repair. We discussed research papers on CNT-based multifunctional hydrogels, electrospun scaffolds, and innovative dressings for bioactive agent delivery, electrical stimulation, and real-time monitoring of wound healing. We also discussed <italic>in vivo</italic> preclinical studies demonstrating significant re-epithelialization and increased angiogenesis, with accelerated wound closure in disease-impaired healing models, such as diabetes. Nevertheless, limitations such as cytotoxicity, impediments to scale-up manufacturing, and regulatory issues hinder direct clinical translation. To overcome these drawbacks, several approaches, such as chemical functionalization, biodegradable CNT derivatives, and hybrid nanocomposites, have been developed. Finally, we describe the translational path for CNT-based wound-healing applications and offer perspectives on future therapeutic interventions for chronic and complex wounds in the context of precision medicine.</p>
</abstract>
<kwd-group>
<kwd>carbon nanotubes</kwd>
<kwd>conductive</kwd>
<kwd>hydrogel</kwd>
<kwd>wound healing</kwd>
<kwd>scaffolds</kwd>
<kwd>angiogenesis</kwd>
</kwd-group>
<funding-group>
<funding-statement>The author(s) declared that financial support was received for this work and/or its publication. SK acknowledges funding support from the Department of Science &#x0026; Technology, New Delhi, through the INSPIRE Faculty Fellowship (Faculty Registration No. IFA21-MS-179).</funding-statement>
</funding-group>
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<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Tissue Engineering and Regenerative Medicine</meta-value>
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</front>
<body>
<sec sec-type="intro" id="s1">
<label>1</label>
<title>Introduction</title>
<p>Wound healing is a well-coordinated, dynamic biological process in which tissue integrity and function are restored after injury. It sequentially follows four overlapping phases, in which the time-line between haemostasis and remodelling is distinct (<xref ref-type="bibr" rid="B73">Wilkinson and Hardman, 2020</xref>), as shown in <xref ref-type="fig" rid="F1">Figure 1</xref>. The haemostatic phase begins immediately after trauma, prevents blood loss via clot formation, and forms a provisional matrix for cell infiltration, thereby promoting healing. This is followed by the inflammatory phase, during which neutrophils and macrophages clear pathogens and debris while releasing cytokines and growth factors to facilitate repair. The proliferative phase, marked by the recruitment and activation of fibroblasts, endothelial cells, and keratinocytes, controls events such as granulation tissue formation, angiogenesis, fibroplasia, and re-epithelialization, leading to wound healing. In the final remodeling or maturation phase, the extracellular matrix (ECM) is strengthened and restructured. During the maturation phase, type III collagen is gradually replaced by type I collagen, restoring tensile strength and functional capacity to the repaired tissue. Although traditionally described as separate stages, wound healing is, in reality, a continuous, overlapping sequence of events that varies with tissue type and differs significantly between acute and chronic wounds (<xref ref-type="bibr" rid="B15">Gonzalez et al., 2016</xref>). Acute wounds usually follow their normal physiological course of healing, with distinct stages, and finally restore tissue integrity within a specified time. In these situations, successful cross-talk among immune cells, fibroblasts, and endothelial cells is essential for timely clotting of the wound, as well as for collagen deposition and re-epithelialization. Chronic wounds, including diabetic ulcers, pressure sores, and leg ulcers, are frequently associated with chronic inflammation, impaired angiogenesis, and microbial infection, which is challenging to treat with conventional methods.</p>
<fig id="F1" position="float">
<label>FIGURE 1</label>
<caption>
<p>Schematic representation of the sequential phases of wound healing and their cellular-molecular regulation. The hemostatic phase involves platelet aggregation, calcium deposition, clot formation, and growth factor release. The inflammatory phase is characterized by neutrophil and macrophage recruitment, ROS generation, bacterial clearance, and macrophage polarization. The next phase involves proliferating cells, such as fibroblasts, keratinocytes, and endothelial cells, which initiate the formation of granulation tissue and angiogenesis. Finally, the remodeling phase includes collagen deposition, ECM maturation, and restoring tensile integrity.</p>
</caption>
<graphic xlink:href="fbioe-13-1732037-g001.tif">
<alt-text content-type="machine-generated">Diagram illustrating the four stages of wound healing: Hemostatic, Inflammation, Proliferation, and Remodeling. Each stage shows changes in skin structure and involved components. Hemostatic involves calcium deposition, clot formation, platelet aggregation, and growth factor release. Inflammation includes immune cells, macrophage polarization, and bacterial control. Proliferation features fibroblast migration, granulation tissue, and angiogenesis. Remodeling involves collagen deposition, re-epithelialization, and scar tissue formation. Each stage has associated processes such as ROS scavenging and ECM production.</alt-text>
</graphic>
</fig>
<p>The conventional method of wound care involves topical antimicrobial ointments, dressings, or systemic pharmacological agents, with primarily symptom-based rather than biological barrier-destructive effects (<xref ref-type="bibr" rid="B50">Pereira and B&#xe1;rtolo, 2016</xref>). Recently, nanotechnology has emerged as a transformative tool for redefining treatment options in biomedicine by developing new products/methods for diagnostics, drug delivery, tissue engineering, and regenerative medicine. This technique is believed to be effective because of its interdisciplinary approach at the nanoscale (1&#xa0;nm&#x2013;100&#xa0;nm) and its ability to enhance size-dependent physicochemical characteristics that are often different from those of bulk materials. In this context, various nanosystems, such as nanoparticles, nanoemulsions, nanocomposites, and nanotubes, have been examined to enhance drug targeting at the wound site, minimize systemic side effects, and improve therapeutic activity (<xref ref-type="bibr" rid="B55">Sangnim et al., 2024</xref>). Among various nanomaterials, carbon-based nanomaterials (including CNTs) are particularly interesting due to their excellent versatility and efficiency in tissue regeneration (<xref ref-type="bibr" rid="B62">Sridhar et al., 2024</xref>).</p>
<p>CNTs are the graphene sheets that are rolled and form nanotubes themselves, appearing as single-walled carbon nanotubes (SWCNTs) diameter 0.4&#x2013;2&#xa0;nm)&#x2002;or multi-walled nanotubes (MWCNTs) with a diameter up to &#x223c;100&#xa0;nm (<xref ref-type="bibr" rid="B65">Thakur et al., 2022</xref>) (<xref ref-type="bibr" rid="B56">Sayed and Shaikh, 2024</xref>). The significance of CNTs in wound repair has primarily been attributed to their outstanding mechanical properties, including tensile strengths of 10&#x2013;100&#xa0;GPa and Young&#x2019;s moduli of 1&#xa0;TPa. CNTs exhibit superior performance compared with most traditional materials and can form strong, tissue-like scaffolds that promote cell adhesion and migration (<xref ref-type="bibr" rid="B19">Holmannova et al., 2022</xref>). Electrically conductive CNTs&#x2002;up to 10<sup>6</sup>&#xa0;S/m promote bioelectrical signalling, influencing cellular behavior in tissues such as skin. Additionally, high thermal conductivity and NIR absorptivity enable the photothermal effect, in which localized heating destroys bacterial membranes with less cytotoxicity to host cells. Furthermore, the availability of a large surface area (up to 1,600&#xa0;m<sup>2</sup>/g) allows for high-capacity loading of drugs such as antibiotics, growth factors, or antioxidants with a controlled drug-releasing profile regulated by pH, temperature, or light. Furthermore, functionalization approaches, including the covalent addition of carboxyl, hydroxyl, or amine groups, or non-covalent wrapping with polymers such as PEG, can make the materials more biocompatible and/or soluble, promote selective delivery, and alleviate some of the potential toxicity of bare CNTs (<xref ref-type="bibr" rid="B37">Madaninasab et al., 2025</xref>), <xref ref-type="fig" rid="F2">Figure 2</xref>.</p>
<fig id="F2" position="float">
<label>FIGURE 2</label>
<caption>
<p>Distinctive physicochemical and biological characteristics of CNTs for wound healing. CNTs have high tensile strength and rigidity, making them suitable for reinforcing scaffolds with greater surface area/aspect ratio, which would afford high drug/gene loading. The electrical conductivity of CNTs enables electrostimulation-induced tissue repair, while their thermal and photothermal conductivities help with infection management and on-demand release. Biological activities include antimicrobial activity, ROS sequestration, and angiogenesis induction, establishing CNTs as a multifunctional nanomaterial for advanced wound treatment.</p>
</caption>
<graphic xlink:href="fbioe-13-1732037-g002.tif">
<alt-text content-type="machine-generated">Diagram showing properties and applications of carbon nanotubes in a circular format. Segments highlight high tensile strength, large surface area, angiogenesis induction, antimicrobial activity, electrical conductivity, reactive oxygen species scavenging, thermal conductivity, and photothermal activity.</alt-text>
</graphic>
</fig>
<p>The significant antimicrobial and immunomodulatory properties of CNTs have tackled key challenges in wound management. The sharp, needle-like structures of CNTs allow mechanical disruption of bacterial membranes, and their surface chemistry promotes the generation of reactive oxygen species (ROS), resulting in intense, broad-spectrum antibacterial activity, even against resistant strains, during the wound-healing process or those formed by biofilm-forming pathogens.</p>
<p>CNTs may also control wound inflammation by scavenging excessive ROS, suppressing pro-inflammatory cytokines, and guiding macrophage polarization toward an anti-inflammatory phenotype, thus providing a microenvironment that favours accelerated tissue repair (<xref ref-type="bibr" rid="B78">Zarouki et al., 2025</xref>). During the proliferative phase, CNT composites promote fibroblast proliferation, collagen synthesis, and angiogenesis through activation of pathways such as PI3K/Akt or ERK/MAPK, sometimes assisted by electrical stimulation or the inclusion of bioactive molecules (<xref ref-type="bibr" rid="B33">Liu and Fang, 2025</xref>). For instance, in a preclinical experiment with CNT-drug-loaded hydrogels, Zhang et al. and their research team achieved 99% healing of diabetic chronic wounds in rodent models after 14 days (<xref ref-type="bibr" rid="B80">Zhang et al., 2023</xref>).</p>
<p>From 2020 to 2025, remarkable developments were made in wound care applications, including CNT-based electrically conductive photothermal and antibacterial scaffolds and functionalized CNTs for targeted drug release. Integration of CNTs with chitosan, PLA, and other biopolymers resulted in nanofibrous dressings with enhanced mechanical strength and antioxidant activity, thereby facilitating faster wound healing in burn and surgical wounds (<xref ref-type="bibr" rid="B67">Vardharajula et al., 2012</xref>) (<xref ref-type="bibr" rid="B56">Sayed and Shaikh, 2024</xref>). Patenting activity indicates the worldwide attention towards developing biodegradable CNT matrices and advanced dressings with sensors. Nevertheless, several barriers remain, including impurity-mediated toxicity, aggregation-induced inflammation, and the lack of scalable, standardized production.</p>
<p>In this review, we start with the structure, classification, and essential properties of CNTs, and summarize their <italic>in vitro</italic> and <italic>in vivo</italic> behaviour related to biological activities associated with wound healing. We review <italic>in vitro</italic> and <italic>in vivo</italic> models that have been utilized as preclinical&#x2002;tools for testing of CNT-based therapeutics, and the broad use of these exciting nanotubes in diverse biomedical applications such as haemostasis, antibacterial or anti-inflammatory systems, diabetic wound healing and angiogenesis, tissue engineering scaffolds, smart-CNT enabled dressings, sensors, and burn-care technologies. The review also explores clinical translation, addressing current advancements, regulatory barriers, and potential solutions to overcome these challenges, and concludes with an outlook for the development of CNT-based wound management technologies.</p>
</sec>
<sec id="s2">
<label>2</label>
<title>Overview, structure, types, and properties of carbon nanotubes</title>
<p>CNT research began with the pioneering discovery of multiwalled CNTs (MWCNTs) by Sumio Iijima in 1991, followed soon after by the identification of single-walled CNTs (SWCNTs). Since then, CNTs have attracted significant attention due to their inherent properties, including mechanical reinforcement, structural diversity, hydrophobicity, flexibility, and electrical conductivity, which make them suitable for applications ranging from nanoelectronics to drug delivery (<xref ref-type="bibr" rid="B53">Roldo and Fatouros, 2013</xref>) (<xref ref-type="bibr" rid="B10">de Andrade et al., 2024</xref>) (<xref ref-type="bibr" rid="B52">Rathinavel et al., 2021</xref>).</p>
<p>CNTs belong to the fullerene structural family and are a third form of carbon (diamond and graphite being the other two). CNTs are seamless cylinders comprising sp<sup>2</sup>-hybridized carbon and can be rolled up to form a hexagonal lattice with superb mechanical, electrical, and thermal properties (<xref ref-type="bibr" rid="B69">Wang et al., 2024a</xref>) (<xref ref-type="bibr" rid="B24">Jia et al., 2024</xref>). The structural orientation of carbon nanotubes (CNTs) can adopt different configurations, such as armchair, zigzag, or chiral, which strongly influences their electronic nature, ranging from metallic to semiconducting (<xref ref-type="bibr" rid="B21">Ijaz et al., 2023</xref>). Based on the number of layers, CNTs are typically divided into SWCNTs and MWCNTs, as shown in <xref ref-type="fig" rid="F3">Figure 3</xref>.</p>
<fig id="F3" position="float">
<label>FIGURE 3</label>
<caption>
<p>Structural representation of <bold>(A)</bold> single walled (SW), <bold>(B)</bold> double walled (DW), <bold>(C)</bold> multi-walled (MW) carbon nanotubes, and <bold>(D)</bold> graphenated CNTs, <bold>(E)</bold> cup stack CNTs resemble stacked cones, and <bold>(F)</bold> torus CNTs are donut-shaped.</p>
</caption>
<graphic xlink:href="fbioe-13-1732037-g003.tif">
<alt-text content-type="machine-generated">Illustration of carbon nanotube types. A: Single-walled (SWCNTs) with a single cylindrical layer. B: Double-walled (DWCNTs) with two concentric layers. C: Multi-walled (MWCNTs) with multiple layers. D: Graphenated CNTs. E: Cup stack CNTs resemble stacked cones. F: Torus CNTs are donut-shaped. Length varies from 0.14 nanometers to 55 centimeters, and diameter from 0.4 nanometers to over 100 nanometers.</alt-text>
</graphic>
</fig>
<sec id="s2-1">
<label>2.1</label>
<title>Single-walled carbon nanotubes (SWCNTs)</title>
<p>SWCNTs are formed from a single sheet of graphene rolled into a tube, with diameters usually between 0.4 and 2&#xa0;nm. Their electrical properties are strongly influenced by their chirality whether the tube is in an armchair, zigzag, or chiral configuration, which determines whether they behave as metals or semiconductors. One of the most notable features of SWCNTs is their exceptionally high surface area, which can reach &#x223c;1,300&#xa0;m<sup>2</sup>/g. This large surface provides abundant sites for drug loading and bioconjugation. The complexes formed when used as drug carriers exhibit prolonged retention in systemic circulation compared with free drugs, enabling sustained cellular uptake via the enhanced permeability and retention (EPR) effect (<xref ref-type="bibr" rid="B20">Hughes et al., 2024</xref>).</p>
<p>Upon targeted delivery, functionalized SWCNTs gradually release their drug payload at the desired site. They are subsequently cleared from the body through the biliary system and excreted in feces. These findings highlight the potential of SWCNTs as efficient nanocarriers, making them promising platforms for drug delivery and wound-healing applications (<xref ref-type="bibr" rid="B2">Anzar et al., 2020</xref>).</p>
</sec>
<sec id="s2-2">
<label>2.2</label>
<title>Multiwalled carbon nanotubes (MWCNTs)</title>
<p>MWCNTs are formed as coaxial cylinders, consisting of several concentric layers of graphene sheets wrapped into the shape of a tube-within-a-tube. They generally have outer diameters of 2&#x2013;100&#xa0;nm and inner diameters of 1&#x2013;3&#xa0;nm. The length of such nanotubes ranges from several nanometres to a few micrometres, depending on the fabrication technique. The multilayered structure of MWCNTs also makes them mechanically stronger and stiffer than SWCNTs (<xref ref-type="bibr" rid="B51">Rahamathulla et al., 2021</xref>). Therefore, they are suitable candidates for applications that require mechanical reinforcement, such as scaffolds in tissue engineering and wound healing. The hollow core with many sidewalls provides high load capacity for therapeutic molecules, making them well-suited as potential drug-delivery carriers. When loaded into biopolymeric scaffolds composed of chitosan, gelatin, alginate, and other biomaterials, MWCNTs instantly enhance cellular adhesion, viability, and proliferation while reducing cytotoxicity (<xref ref-type="bibr" rid="B1">Alhashmi Alamer and Almalki, 2022</xref>).</p>
</sec>
<sec id="s2-3">
<label>2.3</label>
<title>Other variants</title>
<p>In addition to the classical SWCNTs and MWCNTs, several less conventional structural variants of CNTs have been reported, each offering unique physicochemical features. Graphenated CNTs (g-CNTs) consist of CNT backbones decorated with graphene layers, thereby significantly increasing their surface area and electron-transfer efficiency, making them attractive for electrochemical and biomedical applications (<xref ref-type="bibr" rid="B11">Eatemadi et al., 2014</xref>). Cup-stacked CNTs are another variant, composed of truncated-cone-like segments stacked. These structures have thousands of open edges and defect sites, providing a large number of chemical functionalization sites and, in turn, excellent reactivity (<xref ref-type="bibr" rid="B26">Kim et al., 2024</xref>). CNT&#x2002;torus (looped, ring) has been reported. This exotic shape endows unique magnetic and electronic properties, which can have broader applications in CNT-based high-end nanodevices and bioelectronics. In aggregate, these structural changes extend the utility of CNTs, enabling the engineering of desired properties for specific biomedical and technological applications (<xref ref-type="bibr" rid="B65">Thakur et al., 2022</xref>).</p>
</sec>
<sec id="s2-4">
<label>2.4</label>
<title>Properties of CNTs</title>
<p>CNTs possess a high surface area and modifiable surface functionalization, which are beneficial for drug delivery, biosensing, antimicrobial agents, and wound healing. MWCNTs are rigid, multifunctional materials that are particularly appealing for biomedical applications (e.g., fields that require high strength and bioactivity) (<xref ref-type="bibr" rid="B65">Thakur et al., 2022</xref>). The chirality and conformations of CNTs strongly affect their electrical properties: armchair CNTs are metallic, while zigzag and chiral CNTs may be semiconductors. This electrical tunability renders CNTs highly attractive for future materials in electronics and biomedical applications (<xref ref-type="bibr" rid="B7">Costa et al., 2016</xref>).</p>
<p>In addition, CNTs are also well known for their outstanding mechanical strength (tensile strength up to 10&#x2013;100&#xa0;GPa and a Young&#x2019;s modulus of nearly 1&#xa0;TPa), enabling them to withstand high levels of strain without deformation failure (<xref ref-type="bibr" rid="B46">Nurazzi et al., 2021</xref>). They also have&#x2002;high thermal conductivity (2000&#x2013;3000&#xa0;W/mK), outstanding electrical conductivity (10<sup>6</sup>&#x2013;10<sup>7</sup>&#xa0;S/m). Another key feature is their extremely high surface area-to-volume ratio, which would further facilitate interaction with biomolecules and cells. Due to their high aspect ratio (&#x3e;100), they can be used to create conductive percolation networks in polymer composites at very low loading levels (0.1%&#x2013;1%), thereby substantially increasing the material&#x2019;s electrical conductivity (<xref ref-type="bibr" rid="B28">Li et al., 2007</xref>). These characteristics make them suitable for use in efficient heat dissipation and electrical charge transfer applications. These distinct physicochemical attributes of CNTs set them apart from other nanomaterials and are responsible for their growing importance in biomedicine, energy technologies, sensing platforms, and catalytic systems (<xref ref-type="bibr" rid="B16">Gupta et al., 2019</xref>).</p>
<p>Despite CNTs&#x2019; inherent hydrophobicity and tendency to aggregate, biomolecule functionalization can significantly enhance dispersion, biocompatibility, and drug-loading capacity. In biomedical engineering, the exceptional properties of CNTs are considered particularly useful and have been used to fabricate composites with natural polymers such as alginate, collagen, gelatine, and chitosan, or synthetic polymers, to reinforce the mechanical strength of scaffolds, enhance electrical stimulation, and improve cell interactions (<xref ref-type="bibr" rid="B41">Murjani et al., 2022</xref>). Chemical or surface modifications have enabled CNTs to serve as multifunctional platforms in the biomedical field, providing a large surface area and tunable surface chemistry for drug loading (accessible adsorption sites) and structural support from their mechanical strength (<xref ref-type="bibr" rid="B22">Islam et al., 2022</xref>). Their excellent electrical properties have also been used to induce cellular responses, especially in electrically active tissues, including neural, cardiac, and muscular tissues, in which endogenous signals for cell-cell communication are essentially electrical (<xref ref-type="bibr" rid="B43">Nekounam et al., 2021</xref>).</p>
<p>These features render CNTs highly promising in biomedicine, including drug delivery, biosensing, tissue engineering, and wound healing. CNTs possess distinctive physicochemical&#x2002;properties and a broad range of biomedical applications. Their unique combination of mechanical strength, electrical conductivity, and controllable surface chemistry makes them among the most widely investigated nanomaterials in regenerative medicine, drug delivery, and wound healing. With advances in functionalization and toxicity reduction, CNTs are gradually moving towards translational biomedical applications (<xref ref-type="bibr" rid="B16">Gupta et al., 2019</xref>).</p>
</sec>
</sec>
<sec id="s3">
<label>3</label>
<title>Biological activities relevant to wound healing</title>
<p>Wound healing is a complex series of overlapping phases-hemostasis, inflammation,&#x2002;proliferation, and remodelling that involves precisely regulated cellular, molecular, and biochemical events (<xref ref-type="bibr" rid="B57">Sen, 2019</xref>). Disruption of any phase, such as persistent inflammation in diabetic wounds or microbial colonization in chronic ulcers, can compromise healing and lead to non-healing states (<xref ref-type="bibr" rid="B9">Darwin and Tomic-Canic, 2018</xref>). Thus, materials for wound healing need to interact with this complex environment in numerous ways, including promoting each phase, such as hemostasis, managing infection, influencing inflammation, and inducing post-traumatic tissue regeneration. CNTs have various biological outcomes closely associated with these processes owing to their nanoscale size, surface chemistry, and multifunctional nature (<xref ref-type="bibr" rid="B58">Sharma et al., 2016</xref>). Unlike conventional dressings, which are passive barriers to synergies, CNT-based systems become active players within the wound microenvironment and interact with platelets, immune cells, fibroblasts, keratinocytes, endothelial cells, and microbes present at the wound site. Understanding these biological interactions is essential for understanding the therapeutic potential of CNTs in wound healing (<xref ref-type="bibr" rid="B44">Nie et al., 2023</xref>).</p>
<p>CNTs can modulate biological events in wound healing. A very early phase of wound healing is hemostasis, in which blood clotting and the formation of a fibrin plug prevent excessive bleeding and provide a provisional matrix for cellular infiltration. The high surface roughness and fibrous architecture of CNTs replicate the features of extracellular matrix (ECM) proteins that promote platelet adhesion and&#x2002;activation. Numerous experimental studies have shown that CNT dressings promote clotting more efficiently than standard gauze (<xref ref-type="bibr" rid="B37">Madaninasab et al., 2025</xref>). The nanotopography might increase platelet aggregation and stimulate thrombin generation, resulting in accelerated fibrin deposition. Furthermore, CNTs incorporated into polymer hydrogels or sponges showed decreased bleeding time in animal models, suggesting a potential use as hemostatic materials (<xref ref-type="bibr" rid="B81">Zhao et al., 2018</xref>) (<xref ref-type="bibr" rid="B49">Patil et al., 2021</xref>). Rapid hemostasis is critical in trauma or surgical settings, as timely control of bleeding can be lifesaving. The hemostatic enhancement of CNTs is therefore a crucial platform for their application in multifunctional wound dressings.</p>
<p>In addition to blood clotting, another primary concern in wound healing is preventing microbial infection. Bacterial colonization not only retards subsequent healing but also causes chronic inflammation and necrosis. CNTs have intrinsic antimicrobial activity that works through various mechanisms (<xref ref-type="bibr" rid="B3">Baek et al., 2019</xref>). The needle-like sharpness permits direct physical penetration and disruption of the bacterial membrane, leading to leakage of cytoplasmic contents and subsequent cell death. Also, CNTs are capable of generating (spontaneously and/or in light contact) reactive oxygen species (ROS), which may lead to bacterial oxidative stress. Moreover, CNTs exhibit a selective near-infrared (NIR) absorption feature that can be converted into local heat, enabling photothermal antibacterial applications (<xref ref-type="bibr" rid="B17">Hadidi and Mohebbi, 2022</xref>). CNTs under NIR irradiation incorporated into a hydrogel or film can achieve local heating to bactericidal levels, eliminating bacteria and preventing biofilm formation (<xref ref-type="bibr" rid="B82">Zhong et al., 2022</xref>). Significantly, this photothermal modality provides a non-antibiotic treatment option against infections, minimizing the potential risk of antibiotic resistance. Upon combination with antimicrobial peptides (AMPs) and conventional antibiotics, including silver nanoparticles, a synergistic effect was observed, yielding robust, multi-layer coverage against infection when CNTs were utilized (<xref ref-type="bibr" rid="B70">Wang et al., 2024b</xref>).</p>
<p>Although it is essential to control infection, excessive and unresolved inflammation poses another significant barrier to wound healing, particularly in chronic diabetic ulcers. CNTs have been shown to regulate the immune response during healing favourably. Studies suggest that functionalized CNTs influence macrophage polarization, shifting them from the pro-inflammatory M1 phenotype toward the pro-healing M2 phenotype. This shift is associated with decreased release of pro-inflammatory cytokines such as TNF-&#x3b1; and IL-6, on the one hand, and increased expression of anti-inflammatory factors such as IL-10 and TGF-&#x3b2; (<xref ref-type="bibr" rid="B36">Louiselle et al., 2021</xref>). Such immunomodulation helps resolve the inflammatory phase and subsequently allows progression to the proliferative healing phase. In addition, CNTs appear to mitigate oxidative stress in host tissues by scavenging excessive ROS, which is especially useful for wounds with a high burden of oxidative stress that leads to continuous damage during the repair process. These&#x2002;two divergent functions, killing them with ROS in microbes and moderating ROS in host cells, make up just two examples of the many biological interactions that CNTs undertake (<xref ref-type="bibr" rid="B32">Lim et al., 2023</xref>) (<xref ref-type="bibr" rid="B40">Meng et al., 2015</xref>).</p>
<p>As the wound progresses into the proliferative phase, cellular proliferation, angiogenesis, and extracellular matrix deposition predominate. CNTs also interact positively with fibroblasts and keratinocytes, which are crucial cells during this phase. The nanofibrous architecture provides a scaffold-like structure that enhances fibroblast adhesion, spreading, and growth. When embedded within composite hydrogels or nanofibrous mats, CNTs stimulate fibroblast-derived collagen synthesis and thus expedite granulation tissue formation. Keratinocytes, which play a key role in re-epithelialisation, also showed increased migration and proliferation on CNT-modified substrates. The conductive properties of CNTs may also play a role, as bioelectrical cues influence keratinocyte migration during epithelial sheet closure. Electrical stimulation supplied by CNT-based dressings has been reported to augment such processes, illustrating the intertwining of material attributes with biological signalling (<xref ref-type="bibr" rid="B79">Zhang et al., 2021</xref>).</p>
</sec>
<sec id="s4">
<label>4</label>
<title>
<italic>In vitro</italic> and <italic>in vivo</italic> models</title>
<p>Both <italic>in vitro</italic> and <italic>in vivo</italic> models have been used to assess the wound-healing properties of CNT-based materials. Fibroblasts, keratinocytes, and endothelial cells are the three most common cell types used <italic>in vitro</italic> to examine adhesion, proliferation, migration, and ECM deposition. CNT-containing hydrogels and scaffolds have been shown to promote fibroblast growth, collagen production, and keratinocyte migration, ultimately resulting in accelerated re-epithelialization and granulation tissue formation (<xref ref-type="bibr" rid="B83">Zhou et al., 2024</xref>). The electrical conductivity of CNT scaffolds has been shown to enhance gap junction activity and cell communication, particularly when combined with external electrical stimulation, thereby facilitating faster wound closure. Preclinical animal testing, particularly in diabetic rat wound models, has provided clear indications of the translational potential of CNT-based wound dressings. CNT-protein-cellulose hybrid hydrogels accelerated wound contraction and promoted tissue regeneration under NIR irradiation, yielding better healing outcomes than those of conventional controls (<xref ref-type="bibr" rid="B66">Tian et al., 2025</xref>). <italic>In vitro</italic> antibacterial assessments also show that CNT-based composites exert an efficient bactericidal effect against <italic>S. aureus, E. coli</italic>, MRSA, and biofilm-forming bacteria through a series of mechanisms, including physical disruption of the cell membrane, increased ROS generation, and NIR induced photothermal activity. Multifunctional CNT-derived nanocomposite hydrogels have been shown to promote rapid granulation tissue formation, angiogenesis, and re-epithelialization, in addition to sterilizing multidrug-resistant pathogens in infected wounds (<xref ref-type="bibr" rid="B14">Gao et al., 2025</xref>). In addition, multifunctional drug or bioactive-molecule-loaded CNT systems functionalized with agents such as silver nanoparticles have demonstrated synergistic antibacterial and regenerative activities, thereby demonstrating their dual functions of controlling infection whilst promoting tissue repair. In addition, CNT composites with stimuli-responsive elements, i.e., NIR-triggered drug release and antioxidant activities, cleared bacterial biofilms and facilitated tissue regeneration and angiogenesis in rodent wound models (<xref ref-type="bibr" rid="B77">Yang et al., 2025</xref>). The functionalized CNTs incorporated within a biocompatible matrix exhibited low systemic toxicity <italic>in vivo</italic>, highlighting their excellent safety profiles for future clinical applications. Altogether, these studies demonstrate that CNT-based wound-healing systems combine antimicrobial efficacy, immunomodulation, and regenerative assistance, representing a robust, multifunctional platform for effective wound care management (<xref ref-type="bibr" rid="B67">Vardharajula et al., 2012</xref>).</p>
</sec>
<sec id="s5">
<label>5</label>
<title>CNT-based materials for wound healing applications</title>
<p>In recent years, carbon nanotubes (CNTs) have played a pivotal role in biomedical applications, especially in wound healing. Their unique tubular shape, nanoscale rough surface, and potential to create various types of surface chemistry result in a variety of properties spanning structural, electrical, and biochemical domains. Unlike traditional &#x201c;inert&#x201d; dressings that passively cover and protect the wound, most carbon nanotube-based systems can actively participate in the progressive stages involved in the healing cascade. Here, we summarize recent findings by consolidating them into five application areas of wound healing: hemostasis induction, anti-infection efficacy, inflammation alleviation, angiogenesis facilitation, tissue repair stimulation, and on-site chemical changes testing. These studies collectively indicate that CNTs are promising next-generation wound-dressing platforms (<xref ref-type="bibr" rid="B37">Madaninasab et al., 2025</xref>).</p>
<sec id="s5-1">
<label>5.1</label>
<title>Hemostatic applications of CNTs</title>
<p>The initial step of wound management, especially in traumatology, is rapid hemostasis. Hemorrhage continues to be the leading cause of preventable mortality, and traditional dressings such as cotton gauze remain limited to acting as blood absorbents with negligible influence on coagulation. CNT-composites, however, shift this paradigm by introducing a nanoscale architecture that promotes platelet adhesion and fibrin netting formation to facilitate coagulation. Tan et al. reported that the addition of CNTs as fillers to carbonized cellulose aerogels could convert it into a highly efficient hemostatic material (<xref ref-type="bibr" rid="B63">Tan et al., 2025</xref>). Porous and ultralight structures enabled rapid blood absorption, and rough nanosurfaces promoted platelet adhesion/aggregation. In both animal liver and tail bleed <italic>in vivo</italic> models, compared to cellulose (control), the clotting time with CNT-aerogel was shortened by 3-fold, indicating that nanoscale reinforcement is not purely mechanical but also interacts actively with coagulation. Based on the concept of multifunctionality, Wu et al. reported a CNT-based sponge scaffold incorporating pyrrolidonecarboxylic acid zinc (PC<sub>1</sub>Z<sub>2</sub>) for the therapeutic treatment of diabetic wound healing, including inflammation and infection (<xref ref-type="bibr" rid="B74">Wu et al., 2025</xref>), as shown in <xref ref-type="fig" rid="F4">Figure 4</xref>. The CNT network served as a pro-coagulant surface, while the zinc ions exerted antimicrobial and anti-inflammatory properties. This is especially beneficial for diabetic wounds, complicated by trauma-driven infection and inflammation. They showed that combining hemostatic and antimicrobial activities in a single dressing provides dual roles, simultaneously treating multiple early wound-healing challenges. Taken together, these studies demonstrate the transition of CNT-based dressings from passive absorbents into active, multimodal systems. Towards immediate enemy action: CNTs stop immediate bleeding and early infection risks by initiating blood clotting and inhibiting bacterial growth, suggesting significant potential for use in injured patients and even in chronic wound applications.</p>
<fig id="F4" position="float">
<label>FIGURE 4</label>
<caption>
<p>Schematic representation showing the preparation of carbon nanotube-decellularized dermal matrix sponges loaded with zinc-pyrrolidone carboxylate. <bold>(A)</bold> A multifunctional photothermal electroactive sponge scaffold PC<sub>1</sub>Z<sub>2</sub> was fabricated by combining CNTs, PADM (porcine decellularized dermal matrix), and zinc pyrrolidone carboxylate. <bold>(B)</bold> Recovery of the wound&#x2002;with the unique synergistic aspects of conductivity, photothermal effect, immunomodulation, and adsorption. Reproduced with permission from Wu et al. (<xref ref-type="bibr" rid="B74">Wu et al., 2025</xref>).</p>
</caption>
<graphic xlink:href="fbioe-13-1732037-g004.tif">
<alt-text content-type="machine-generated">Diagram showing a multifunctional composite material. Part A depicts the synthesis of PC1Z2, combining CNTs, porcine decellularized dermal matrix(PADM), and zinc pyrrolidone carboxylate. Part B illustrates four therapeutic effects: conductivity for cell migration and revascularization, photothermal effect for antibacterial action and improved wound metabolism, L-PCA for anti-inflammatory immunomodulation, and adsorption for hemostasis. Each effect is visually represented with arrows and symbols indicating processes like ion interaction, laser application, and cell response.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s5-2">
<label>5.2</label>
<title>Antibacterial and anti-inflammatory systems</title>
<p>Once bleeding is stopped, wounds are at high risk of infection. Bacterial colonization delays healing and results in chronic inflammation, which may cause systemic complications. CNTs have been well established for their intrinsic antibacterial activities due to their hydrophobicity, membrane-puncturing potential, and ability to generate reactive oxygen species (ROS) (<xref ref-type="bibr" rid="B39">Maleki Dizaj et al., 2015</xref>). In a recent study, researchers fabricated a hydrogel-based composite system incorporating silver nanoparticles (AgNPs), MWCNTs, and Pluronic F127 to manage bacterial infection at the wound site, thereby imparting antioxidant and antimicrobial properties. The MWCNT-Ag/PF127 composites were demonstrated for enhanced antibacterial and anti-biofilm activities while maintaining a balance between bioactive properties and biocompatibility (<xref ref-type="bibr" rid="B54">Ryu et al., 2025</xref>). On the catalytic front, Wang et al. described hydrophobic Fe/Co-loaded CNTs (<xref ref-type="bibr" rid="B5">Chen et al., 2025</xref>). These composites disrupted bacterial membranes and generated ROS, resulting in effective bactericidal activity against both gram-positive and gram-negative strains. Their lipophilicity promoted close contact between bacterial membranes, thereby increasing permeabilization. Photothermal designs are another major direction for these studies. Chao et al. constructed CNT-lignin/PVA hydrogels that can induce local hyperthermia upon NIR irradiation at the wound site with the improved antibacterial activity against <italic>E. coli</italic> and <italic>S. aureus</italic> (<xref ref-type="bibr" rid="B4">Chao et al., 2023</xref>). <italic>In vivo</italic> studies demonstrated on-demand elimination of pathogen propagation at the wound site through a photothermal antibacterial effect, reduced inflammation, and rapid wound healing. Li et al. engineered CNT hydrogels exhibiting catalase and superoxide dismutase-mimicking &#x201c;nanozyme&#x201d; activity (<xref ref-type="bibr" rid="B1">Alhashmi Alamer and Almalki, 2022</xref>). These hydrogels simultaneously killed bacteria and scavenged ROS to re-establish redox homeostasis at the wound site. This dual-action system represents a significant innovation, as CNT composites can eradicate pathogens, modulate the inflammatory microenvironment, and facilitate angiogenesis. In another study, OuYang et al. introduced a carbon nanotube-based injectable nanoconductive hydrogel with a host-guest supramolecular macromolecule approach. The authors used single-walled carbon nanotubes to fabricate an endogenously electric-field-responsive hydrogel that promotes rapid migration of multiple cells at the wound site. In addition, the hydrogel was encapsulated with endothelial cell growth supplement for cell proliferation, and N-Formyl-Methionyl-Leucyl-phenylalanine to recruit neutrophils and induce Neutrophil Extracellular Traps. Altogether, the hydrogel modulates the inflammatory response, provides antimicrobial activity, and repairs wounds (<xref ref-type="bibr" rid="B47">Ou et al., 2025</xref>), as shown in <xref ref-type="fig" rid="F5">Figure 5</xref>.</p>
<fig id="F5" position="float">
<label>FIGURE 5</label>
<caption>
<p>Schematic representation of nanomaterial-assisted wound healing mechanisms. <bold>(A)</bold> An infected wound area was treated with injectable hydrogel in mice for localized treatment. <bold>(B)</bold> The hydrogel is thermostable, maintaining its integrity at body temperature and enabling stable release of therapeutic cargo. <bold>(C)</bold> The hydrogel promotes NETosis, thereby enhancing antimicrobial activity and recruiting cells for tissue migration and healing <bold>(D)</bold>. Mechanistically, NETosis in neutrophils is regulated by the Ncf1 gene, GC-GR signaling, and mitochondrial ROS, thereby promoting DNA release to facilitate effective infection control. Reproduced with permission from OuYang et al. (<xref ref-type="bibr" rid="B47">Ou et al., 2025</xref>).</p>
</caption>
<graphic xlink:href="fbioe-13-1732037-g005.tif">
<alt-text content-type="machine-generated">Illustration of a medical treatment process involving hydrogel. Panel A shows a mouse with an infected wound receiving an injectable hydrogel. Panel B details the thermosensitive and UV-stabilized EF@S-HGM hydrogel preparation. Panel C depicts antimicrobial and NETosis effects on tissue with electrical current influence. Panel D illustrates cellular mechanisms, including ROS production, NETosis, and DNA release. A legend describes symbols for materials and processes such as acrylate-&#x03B2;-cyclodextrin (Ac-&#x03B2;-CD), gelatin, and reactive oxygen species.</alt-text>
</graphic>
</fig>
<p>In another example of developing advanced systems for bioelectronic stimulation, Nie et al. developed mechano-electric CNT hydrogels that provided both antimicrobial action and electrical stimulation, thereby enhancing fibroblast migration and proliferation (<xref ref-type="bibr" rid="B45">Nie et al., 2025</xref>). Building on this, Xu et al. created a self-powered casein-CNT &#x201c;E-dressing&#x201d; capable of harvesting biomechanical energy from wound movement to deliver electrical cues, while also exhibiting photothermal antibacterial activity under NIR irradiation <xref ref-type="bibr" rid="B76">Xu et al., 2025</xref>. In the context of electronic skin (E-skin) devices, Song et al. fabricated thermoelectric CNT-polymer composites with dual antibacterial and thermoreceptor-like activity, pointing toward integrated sensory applications with self-healing properties (<xref ref-type="bibr" rid="B61">Song et al., 2025</xref>). Another study reported by Xu et al. demonstrated the development of CNT-GelMA-based electroactive macroporous nanocomposite hydrogels via pickering emulsions, combining antibacterial activity with structural porosity to facilitate cellular infiltration and enhance wound-healing performance. The mechanical performance, aside from pore dimensions and conductivity, can also be tailored by varying the CNT content (<xref ref-type="bibr" rid="B75">Xu et al., 2020</xref>). In a study aimed at developing treatments for anal fistula, Wang et al. developed quaternized CNT molecular brush grafted injectable microgel systems to effectively fill the fistula and facilitate the drainage of exudate with antibacterial and anti-inflammatory effects, as shown in <xref ref-type="fig" rid="F6">Figure 6</xref> (<xref ref-type="bibr" rid="B71">Wang et al., 2025a</xref>). Related investigations also highlighted multifunctional hydrogels with bacteriostatic, self-healing, conductive, and drug-delivery properties (<xref ref-type="bibr" rid="B78">Zarouki et al., 2025</xref>) (<xref ref-type="bibr" rid="B27">Lai et al., 2025</xref>). Overall, CNTs are not limited to antibacterial action through a single mechanism but instead contribute multiple strategies, including ROS generation, photothermal conversion, enzymatic mimicry, and electrical stimulation. This versatility enables tailored dressings for both acute trauma and chronic infection, providing a robust foundation for future multimodal infection-control systems.</p>
<fig id="F6" position="float">
<label>FIGURE 6</label>
<caption>
<p>Schematic representation of the drainage and anti-inflammatory role of quaternized molecular brush-grafted injectable microgel (denoted as GAA@CNT-g-PVBTMA) in anal fistula repair. <bold>(a)</bold> In conventional anal seton surgery, the seton ensures continuous drainage of exudates but lacks the ability to fill the fistula tract. Exposure to ongoing inflammatory triggers and promotes aberrant epithelial growth along the fistula wall, impeding closure and healing process. <bold>(b)</bold> The GAA@CNT-g-PVBTMA microgel binds negatively charged inflammatory cytokines through electrostatic interactions, while simultaneously providing structural filling, controlled drainage, and anti-inflammatory activity, thereby supporting effective fistula healing. Reproduced with permission from <xref ref-type="bibr" rid="B71">Wang et al. (2025a)</xref>.</p>
</caption>
<graphic xlink:href="fbioe-13-1732037-g006.tif">
<alt-text content-type="machine-generated">Comparison of seton and microgel applications in medical treatment for inflammation. The top row illustrates the seton method, indicating ineffective filling, inadequate drainage, and lack of anti-inflammatory effects. The bottom row depicts microgel application, showing effective filling, adequate drainage, and anti-inflammatory benefits. The diagram includes symbols for TNF-alpha, IL-1 beta, epithelial cells, inflammatory cells, and chemical structures related to the microgel composition.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s5-3">
<label>5.3</label>
<title>CNTs in diabetic wound repair and angiogenesis</title>
<p>Diabetic ulcers are&#x2002;one such clinical challenge, where the wound is usually impaired due to angiogenesis deficiency, mitochondrial dysfunction, and inflammation. CNT-based&#x2002;materials have been used to address these problems by combining bioactive delivery systems with conductive scaffolds. Zhang et al. synthesized an exosome/metformin self-healing conductive hydrogel using MWCNTs to promote chronic diabetic wound healing by interfering with mitochondrial fission (<xref ref-type="bibr" rid="B80">Zhang et al., 2023</xref>). The synthesized CNT-based injectable hydrogel sustained the release of exosomes and metformin, attenuated mitochondrial fission, normalized endothelial dysfunction, and induced angiogenesis, thereby interfering with the pathogenesis of diabetic ulcers at both the level of metabolic control and conductive signalling, as shown in <xref ref-type="fig" rid="F7">Figure 7</xref>. In another study, Khalid et al. designed CNT-functionalized bacterial cellulose biomaterials to enhance fibroblast migration and angiogenic responses, thereby expediting the healing process in a diabetic wound model (<xref ref-type="bibr" rid="B25">Khalid et al., 2022</xref>). Tavakoli et al. employed a tri-layer CNT sponge scaffold incorporating insulin-like growth factor-1 for sustained delivery, to promote prolonged angiogenic signalling, durable vascular remodelling, and a faster rate of wound closure (<xref ref-type="bibr" rid="B64">Tavakoli et al., 2023</xref>). Recently, Naik et al. developed CNT-protein-cellulose-based conductive hydrogels for photothermal therapy and demonstrated <italic>in vivo</italic> photoacoustic imaging in a diabetic disease model (<xref ref-type="bibr" rid="B42">Naik et al., 2025</xref>). Here, the dual-purpose platform facilitated significantly faster, more effective wound closure while simultaneously monitoring vascular progression non-invasively, representing a significant breakthrough in diabetic wound care. These studies demonstrate the multifunctional potential of CNT composites, where conductivity, structural reinforcement, and therapeutic delivery converge. Such systems hold considerable promise for diabetic wound healing as they enhance angiogenesis, correct endothelial dysfunction, and stimulate fibroblast activity.</p>
<fig id="F7" position="float">
<label>FIGURE 7</label>
<caption>
<p>PEG/Ag/CNT-M &#x2b; E hydrogel (polyethylene glycol/silver/carbon nanotube-metformin and exosome) enhances diabetic wound healing by inhibiting mitochondrial fission (anti-fission), reducing mitochondrial reactive oxygen species, promoting vascular endothelial cell (VEC) proliferation, and stimulating angiogenesis. Reproduced with permission from <xref ref-type="bibr" rid="B80">Zhang et al. (2023)</xref>.</p>
</caption>
<graphic xlink:href="fbioe-13-1732037-g007.tif">
<alt-text content-type="machine-generated">Diagram illustrating the application of PEG/Ag/CNT-M+E hydrogel on a diabetic wound in a mouse. The hydrogel inhibits mitochondrial fission, reduces mitochondrial reactive oxygen species (mt-ROS), and promotes vascular endothelial cell proliferation and angiogenesis. Key components include mitochondria, vascular endothelial cells, and blood vessels, highlighting improved healing processes.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s5-4">
<label>5.4</label>
<title>Tissue engineering and regenerative scaffolds</title>
<p>Apart from treatment for diabetic-related diseases, CNTs have been incorporated into regenerative scaffolds to enhance fibroblast activity, keratinocyte migration, stem cell therapies, and drug delivery. CNTs&#x2019; conductivity enables scaffolds to transmit bioelectric signals, while mechanical reinforcement improves structural stability. Liu et al. demonstrated that chitosan/gelatin/MWCNT scaffolds under electrical stimulation show enhanced fibroblast proliferation and elevated expression of type I and type III collagen compared with non-conductive counterparts (<xref ref-type="bibr" rid="B35">Liu et al., 2025</xref>). Forero-Doria et al. reported supramolecular CNT-cellulose hydrogels for sustained release of bioactive compounds with antimicrobial and <italic>in vivo</italic> wound-healing regenerative benefits (<xref ref-type="bibr" rid="B12">Forero-Doria et al., 2020</xref>). Wang et al. reported cellulose/polypyrrole/CNT-based electroactive hydrogels for enhanced cell proliferation under electrical stimulation in wound healing (<xref ref-type="bibr" rid="B68">Wang et al., 2020</xref>). Li et al. expanded the functionality of CNTs by fabricating self-healing hydrogels that retain conductivity and mechanical integrity under repeated deformation (<xref ref-type="bibr" rid="B29">Li et al., 2020</xref>). Recently, Chen et al.&#x27;s research group constructed an electroactive, oriented wound dressing using a CNT-aligned nanofibrous sheet, which provides directional cues for fibroblast and endothelial cell proliferation and migration, thereby accelerating the healing process (<xref ref-type="bibr" rid="B5">Chen et al., 2025</xref>). <xref ref-type="fig" rid="F8">Figure 8</xref> represents the fabrication of PCL/Gelatin/CNT scaffolds via electrospinning to provide electrostimulation (ES) and regulate the immune microenvironment. CNTs also provide conductivity, enabling the coupling of surrounding and applied electric fields to regulate macrophage phenotypes from M1 to M2 and promote the fibroblast and endothelial cell migration. <italic>In vivo</italic> studies showed that PCL/Gelatin/CNT scaffolds treated with electrical stimulation inhibited the early inflammation with increased angiogenesis and collagen deposition. Such dressing provides an efficient ES-assisted method for wound healing. In another report, Hashemi et al. and the research group seeded human Wharton&#x2019;s jelly stem cells tagged with superparamagnetic iron oxide nanoparticles onto PVA/chitosan/CNT scaffolds to study their effect on burn wounds. The outcomes of their study include enhanced healing of burn wounds and MRI monitoring of transplanted cells, highlighting their clinical relevance (<xref ref-type="bibr" rid="B18">Hashemi et al., 2025</xref>). In the research reported by Cui et al., an electrospun PCL/CNT fibrous scaffold system was coated with polydopamine containing basic fibroblast growth factor (bFGF) to promote tissue regeneration (<xref ref-type="bibr" rid="B8">Cui et al., 2024</xref>). Encapsulation of CNTs modulates the immune microenvironment by promoting macrophage polarization from M1 to M2. As shown in <xref ref-type="fig" rid="F9">Figure 9</xref>, the electroactive aligned fibres can promote fibroblast proliferation and guide cell assembly. <italic>In vitro</italic> and <italic>in vivo</italic> studies showed decreased inflammation, enhanced granulation tissue, increased collagen deposition, and re-epithelialization. Altogether, these studies portray CNT scaffolds as bioelectronic regenerative platforms that integrate cell guidance, drug delivery, and self-healing functions. They are versatile enough to support both routine wound closure and advanced strategies such as stem cell transplantation.</p>
<fig id="F8" position="float">
<label>FIGURE 8</label>
<caption>
<p>Schematic representation of the fabrication of the PCL/GE/CNT electroactive scaffold based on CNTs using the electrospinning method and combined with electrical stimulation (ES) for skin repair. By differentiating macrophages, fibroblasts, and endothelial cells, the scaffold with local ES supports wound healing through early remodelling of the inflammatory microenvironment and by inducing re-epithelialization and collagen deposition. Reproduced with permission from (<xref ref-type="bibr" rid="B5">Chen et al., 2025</xref>).</p>
</caption>
<graphic xlink:href="fbioe-13-1732037-g008.tif">
<alt-text content-type="machine-generated">Diagram illustrating a wound healing process using a composite of PCL, gelatin, and carbon nanotubes with electrical stimulation on a mouse. The healing is shown in three phases: inflammation, proliferation, and remodeling. Key cellular components include macrophages (M1 and M2), fibroblasts, collagen types I and III, and various growth factors, all influenced by the composite and electrical stimulation.</alt-text>
</graphic>
</fig>
<fig id="F9" position="float">
<label>FIGURE 9</label>
<caption>
<p>The first row shows the schematic of scaffold fabrication, starting from PCL (polycaprolactone) and CNT, followed by PDA (polydopamine) coating and bFGF (basic fibroblast growth factor) loading, and application to a murine wound model. The second row shows the immune regulation stage, with PDA reducing ROS (reactive oxygen species) and transforming macrophages from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotypes, whereas in the wound-healing stage, bFGF accelerates fibroblast proliferation, migration, granulation, and collagen (Col I/III) deposition. Reproduced with permission from (<xref ref-type="bibr" rid="B8">Cui et al., 2024</xref>).</p>
</caption>
<graphic xlink:href="fbioe-13-1732037-g009.tif">
<alt-text content-type="machine-generated">Diagram illustrating the process of wound healing with PCL/CNT-PDA-bFGF in mice. The top section shows the chemical preparation of PCL/CNT-PDA-bFGF. The middle section depicts the wound healing process in two stages: immune regulation and wound healing. The immune regulation stage involves ROS transformation and immune cell signaling. The wound healing stage focuses on proliferation, migration, collagen deposition, and granulation. The lower section includes a legend identifying various components like M1, M2, PDA, bFGF, and collagen types.</alt-text>
</graphic>
</fig>
</sec>
<sec id="s5-5">
<label>5.5</label>
<title>Smart CNT dressings, sensors, and burn management</title>
<p>Recent advancements towards wound management include the development of innovative dressings that integrate therapeutic and sensing capabilities. CNTs&#x2019; conductivity, flexibility, and photothermal properties position them as prime candidates for bioelectronic skins and responsive hydrogel systems. Recently, Ji et al. synthesized CNT-based hydrogel bandage containing glucose and pH sensors for non-invasive monitoring of diabetic wounds (<xref ref-type="bibr" rid="B23">Ji et al., 2025</xref>). Liu et al. fabricated an electronic skin scaffold with therapeutic and diagnostic capabilities (<xref ref-type="bibr" rid="B34">Liu et al., 2023</xref>). Shen et al. reported a CNT-based nanocomposite conductive hydrogel for flexible monitoring of human motion in daily life and for detecting local temperature changes to monitor the wound-healing process (<xref ref-type="bibr" rid="B59">Shen et al., 2023</xref>). Song et al. developed a temperature-responsive electronic platform using a CNT-based thermoelectric polymer composite with self-healing and stretchable properties (<xref ref-type="bibr" rid="B61">Song et al., 2025</xref>). Shi et al. have fabricated a novel CNT-based hydrogel with heat-storage capacity, thermal-conductivity, and adhesive ability properties. Thus, CNTs are a potential candidate for burn therapy, laser treatment, and heat-protective clothing (<xref ref-type="bibr" rid="B60">Shi et al., 2022</xref>). Pantzke et al. reported that CNTs can modulate interactions between CNTs and fibers in the lungs of&#x2002;patients with pulmonary fibrosis, highlighting the importance of detailed long-term biosafety assessment as CNT-based dressings approach clinical use (<xref ref-type="bibr" rid="B48">Pantzke et al., 2023</xref>). Together, these intelligent systems exemplify the progression of CNTs applications: active dressings capable of sensing, stimulating, and healing in real time, accompanied by safety assessments to ensure clinical translation.</p>
</sec>
</sec>
<sec id="s6">
<label>6</label>
<title>Clinical translation and challenges</title>
<p>The translation of carbon nanotube (CNTs)-based materials from preclinical research to clinical practice holds immense potential to revolutionize wound healing, particularly for chronic wounds such as diabetic ulcers, venous leg ulcers, and burns. However, significant hurdles remain in achieving regulatory approval, ensuring safety, and scaling production. This section outlines the current state of clinical translation, key challenges, and strategies to overcome them, drawing on recent studies and patents from 2020 to 2025.</p>
<sec id="s6-1">
<label>6.1</label>
<title>Current progress in clinical translation</title>
<p>CNT-based wound healing materials have shown promise in preclinical models, with applications ranging from antimicrobial dressings to regenerative scaffolds. For instance, bacterial cellulose/MWCNT films achieved 99% wound closure in diabetic rat models within 21 days (<xref ref-type="bibr" rid="B25">Khalid et al., 2022</xref>), and CNT/GelMA demonstrated rapid hemostasis and sustained drug release in murine wounds (<xref ref-type="bibr" rid="B30">Li et al., 2022a</xref>) (<xref ref-type="bibr" rid="B81">Zhao et al., 2018</xref>). Early-phase clinical trials, primarily conducted in Asia and Europe, are largely centered on evaluating CNT-hydrogel composites for use in burn and surgical wounds, with a focus on safety and efficacy. Patents from 2023 to 2024 describe CNT-based dressings with integrated sensors for real-time wound monitoring, indicating industry interest in clinical applications (<xref ref-type="bibr" rid="B20">Hughes et al., 2024</xref>). However, no CNT-based wound healing product has yet received widespread regulatory approval (e.g., FDA or EMA), reflecting the nascent stage of translation.</p>
<p>Toxicity Concerns: A primary barrier is the potential cytotoxicity of CNTs, particularly pristine forms, which can induce inflammation, oxidative stress, or genotoxicity due to impurities (e.g., metal catalysts) or aggregation. Long-term bioaccumulation of non-biodegradable CNTs, especially MWCNTs, raises concerns about systemic toxicity, as they may persist in tissues or translocate to organs like the lungs or liver (<xref ref-type="bibr" rid="B6">Cheng et al., 2022</xref>). Functionalization with biocompatible groups (e.g., PEG, carboxyl) mitigates these risks; however, studies show variable biocompatibility depending on the CNT type, size, and dose. For example, high-dose SWCNTs (&#x3e;1&#xa0;mg/mL) caused fibroblast apoptosis <italic>in vitro</italic>, while low-dose functionalized CNTs (0.1&#x2013;0.5&#xa0;wt%) were well-tolerated (<xref ref-type="bibr" rid="B13">Fraser et al., 2020</xref>). Comprehensive toxicological profiling in complex models (e.g., porcine or humanized systems) is needed to establish safe exposure limits (<xref ref-type="bibr" rid="B56">Sayed and Shaikh, 2024</xref>).</p>
<p>Scalability and Cost: Producing high-purity CNTs at scale remains costly, with prices ranging from $50 to $ 500/g for biomedical-grade materials. Synthesis methods, such as chemical vapor deposition (CVD), require expensive catalysts and energy-intensive processes, while purification to remove impurities adds complexity. Scaling fabrication of CNTs composites, such as hydrogels or electrospun mats, is challenging due to difficulties in achieving uniform CNT dispersion and reproducibility. These factors limit cost-effectiveness, a critical consideration for widespread clinical adoption, especially in resource-limited settings (<xref ref-type="bibr" rid="B38">Madikere Raghunatha Reddy et al., 2025</xref>).</p>
<p>Regulatory Hurdles: Regulatory and translational challenges remain major hurdles for bringing CNT-based wound dressings into clinical use. Regulatory bodies require extensive, continuous data on biocompatibility, biodegradation, systemic distribution, and manufacturing consistency. However, CNT materials are intrinsically heterogeneous, varying in diameter, length, chirality, purity (metallic or semiconducting), surface chemistry, and degree of functionalization, which complicates the establishment of uniform toxicity tests and consistent batch-to-batch standards. This variability can lead to impurity-mediated cytotoxicity, endotoxin contamination, and unpredictable inflammatory responses.</p>
<p>Current nanomaterial standards, such as ISO/TS 80004, provide only high-level definitions and lack CNTs-specific protocols for assessing safety, degradation kinetics, sterility assurance, or long-term tissue retention. As a result, regulators must evaluate CNT-based devices individually, resulting in slowing the review process and hindering industrial translation. The clinical pipeline faces similar constraints, with a scarcity of long-term preclinical studies and an almost complete absence of randomized controlled clinical trials. Without robust human data in chronic wounds, burns, or diabetic ulcers, CNT-based dressings remain confined to laboratory and small-animal research.</p>
<p>Strategies to overcome challenges: Advances in purification techniques, such as acid washing and ultracentrifugation, reduce impurities, while biodegradable CNT derivatives (e.g., carboxylate CNTs) minimize bioaccumulation risks. Developing cost-effective synthesis methods, such as plasma-enhanced CVD, and scalable fabrication techniques (e.g., automated 3D printing) could lower costs. Collaborative efforts between academia, industry, and regulators are essential to establish standardized testing protocols and accelerate clinical trials. Emerging translational platforms, including injectable hydrogels, microneedle patches, and 3D-printed scaffolds, offer scalable, multifunctional strategies for clinical deployment. These approaches emphasize integrating nanomaterials with imaging-guided and precision-medicine paradigms.</p>
</sec>
</sec>
<sec id="s7">
<label>7</label>
<title>Future perspectives</title>
<p>The future direction of CNTs for wound-healing materials is to establish multifunctional, patient-specific platforms utilising advanced technologies to overcome the above limitations. The key directions include biodegradable CNTs, novel wound dressings, and possible synergy with new intervention(s). Biodegradable CNTs prepared by oxidative cleavage or enzymatic degradation could minimise long-term toxicity and allow safe elimination from the body. Studies of graphite oxides may guide the development of CNTs. Innovative dressings with embedded sensors to monitor pH, temperature, or markers of infection, combined with AI-based analytics, herald personalised therapy. For example, a 2024 patent introduced a real-time monitor and NIR-triggered drug-release CNT hydrogel for adaptive treatment. Combining CNTs with gene therapy (e.g., siRNA delivery) or stem cell scaffolding may improve regeneration, particularly in chronic wounds. Technical advances in 3D bioprinting and nanotechnology may enable the fabrication of customised scaffolds for multidimensional wounds in the future, and multicentre clinical studies with large sample sizes will further verify their therapeutic effects. Shared efforts to lower costs and normalise regulation will be key to commercialisation, which could revolutionise wound care over the next decade.</p>
</sec>
<sec sec-type="conclusion" id="s8">
<label>8</label>
<title>Conclusion</title>
<p>CNTs have tremendous potential for wound healing due to their distinctive mechanical, electrical, and thermal properties, enabling the fabrication of advanced wound dressings that address infection and inflammation and facilitate tissue regeneration. To maintain a broad perspective, <xref ref-type="table" rid="T1">Table 1</xref> presents&#x2002;CNT-based wound-healing approaches, including the mechanisms and primary outcomes discussed above. This integrative map makes evident that CNT composites encompass haemostasis, infection prevention, immunomodulation, angiogenesis, and regenerative scaffolding. Functionalized CNT-based platforms, such as hydrogel scaffolds, have shown preclinical efficacy, and several of these studies are now entering early-phase clinical trials. However, these cellular materials can only be further developed into viable products after toxicity and scale-up are addressed through improved purification strategies for purity, biodegradable system design, and standardisation. Over time, innovative wound treatments, whether that be smart systems, AI, or regenerative therapies, will revolutionise the treatment of chronic wounds, resulting in better patient outcomes and reduced healthcare burdens.</p>
<table-wrap id="T1" position="float">
<label>TABLE 1</label>
<caption>
<p>Summary of carbon nanotube (CNT)-based wound healing studies highlighting material systems, mechanisms, and outcomes.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="left">Category</th>
<th align="left">CNT system/Composite</th>
<th align="left">Key mechanism(s)</th>
<th align="left">Model/Outcome</th>
<th align="left">Ref. no.</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left">Hemostatic</td>
<td align="left">CNT-cellulose aerogel</td>
<td align="left">Nanosurface promotes platelet adhesion, fibrin mesh</td>
<td align="left">
<italic>In vivo</italic> liver and tail bleeding leads to 3&#xd7; faster clotting</td>
<td align="left">
<xref ref-type="bibr" rid="B63">Tan et al. (2025)</xref>
</td>
</tr>
<tr>
<td align="left">Hemostatic</td>
<td align="left">CNT-zinc sponge</td>
<td align="left">CNT as pro-coagulant surface; Zn<sup>2&#x2b;</sup> as antimicrobial and anti-inflammatory</td>
<td align="left">Diabetic wounds: &#x2193;IL-6/TNF-&#x3b1;, &#x2191;VEGF/TGF-&#x3b2;1, enhanced neovascularization</td>
<td align="left">
<xref ref-type="bibr" rid="B74">Wu et al. (2025)</xref>
</td>
</tr>
<tr>
<td align="left">Antibacterial/Anti-inflammatory</td>
<td align="left">Fe/Co-loaded CNTs</td>
<td align="left">Hydrophobic, ROS generation, bacterial membrane disruption</td>
<td align="left">Broad-spectrum antibacterial</td>
<td align="left">
<xref ref-type="bibr" rid="B72">Wang et al. (2025b)</xref>
</td>
</tr>
<tr>
<td align="left">Antibacterial/Anti-inflammatory</td>
<td align="left">CNT-lignin/PVA hydrogel</td>
<td align="left">NIR photothermal antibacterial; adaptable elastic hydrogel</td>
<td align="left">Pathogen eradication under NIR</td>
<td align="left">
<xref ref-type="bibr" rid="B4">Chao et al. (2023)</xref>
</td>
</tr>
<tr>
<td align="left">Antibacterial/Anti-inflammatory</td>
<td align="left">molybdenum disulfide nanosheet/CNT &#x201c;nanozyme&#x201d; hydrogel</td>
<td align="left">Catalase/SOD mimicry, ROS scavenging</td>
<td align="left">Bactericidal &#x2b; redox homeostasis</td>
<td align="left">
<xref ref-type="bibr" rid="B31">Li et al. (2022b)</xref>
</td>
</tr>
<tr>
<td align="left">Antibacterial/Anti-inflammatory</td>
<td align="left">Injectable conductive CNT hydrogel &#x2b; EGF factors</td>
<td align="left">Neutrophil recruitment, NETs, vascular remodeling</td>
<td align="left">Infected wound healing</td>
<td align="left">
<xref ref-type="bibr" rid="B47">Ou et al. (2025)</xref>
</td>
</tr>
<tr>
<td align="left">Antibacterial/Anti-inflammatory</td>
<td align="left">Zn NPs/CNTs/PNIPAM</td>
<td align="left">Electrical stimulation &#x2b; antimicrobial</td>
<td align="left">Enhanced fibroblast migration and proliferation</td>
<td align="left">
<xref ref-type="bibr" rid="B45">Nie et al. (2025)</xref>
</td>
</tr>
<tr>
<td align="left">Antibacterial/Anti-inflammatory</td>
<td align="left">Casein-CNT &#x201c;E-dressing&#x201d;</td>
<td align="left">Self-powered, NIR photothermal &#x2b; electrical cues</td>
<td align="left">Chronic wound management</td>
<td align="left">
<xref ref-type="bibr" rid="B76">Xu et al. (2025)</xref>
</td>
</tr>
<tr>
<td align="left">Antibacterial/Anti-inflammatory</td>
<td align="left">Thermoelectric CNT-polymer composites</td>
<td align="left">Thermoreceptor-like &#x2b; antibacterial</td>
<td align="left">Integrated sensory dressings</td>
<td align="left">
<xref ref-type="bibr" rid="B61">Song et al. (2025)</xref>
</td>
</tr>
<tr>
<td align="left">Antibacterial/Anti-inflammatory</td>
<td align="left">Macroporous CNT/gelatin methacryloyl. hydrogels</td>
<td align="left">Porosity &#x2b; antibacterial</td>
<td align="left">Cellular infiltration &#x2b; antibacterial</td>
<td align="left">
<xref ref-type="bibr" rid="B75">Xu et al. (2020)</xref>
</td>
</tr>
<tr>
<td align="left">Antibacterial/Anti-inflammatory</td>
<td align="left">Quaternized CNT microgels</td>
<td align="left">Injectable, drainage &#x2b; antibacterial</td>
<td align="left">Anal fistula repair, anti-inflammatory</td>
<td align="left">
<xref ref-type="bibr" rid="B71">Wang et al. (2025a)</xref>
</td>
</tr>
<tr>
<td align="left">Diabetic wound healing</td>
<td align="left">CNT&#x2013;protein&#x2013;cellulose conductive hydrogel</td>
<td align="left">Photothermal therapy &#x2b; PA imaging</td>
<td align="left">Diabetic rat: closure &#x2b; vascular monitoring</td>
<td align="left">
<xref ref-type="bibr" rid="B42">Naik et al. (2025)</xref>
</td>
</tr>
<tr>
<td align="left">Diabetic wound healing</td>
<td align="left">CNT hydrogel &#x2b; exosomes and metformin</td>
<td align="left">Suppressed mitochondrial fission, corrected endothelial dysfunction</td>
<td align="left">Enhanced angiogenesis in diabetic ulcers</td>
<td align="left">
<xref ref-type="bibr" rid="B80">Zhang et al. (2023)</xref>
</td>
</tr>
<tr>
<td align="left">Diabetic wound healing</td>
<td align="left">CNT-functionalized bacterial cellulose</td>
<td align="left">Enhanced fibroblast migration &#x2b; angiogenic response</td>
<td align="left">Faster closure in diabetic wounds</td>
<td align="left">
<xref ref-type="bibr" rid="B25">Khalid et al. (2022)</xref>
</td>
</tr>
<tr>
<td align="left">Diabetic wound healing</td>
<td align="left">polycaprolactone/gelatin/CNT</td>
<td align="left">Increased expression of Col I/III and VEGF, angiogenesis, vascular remodeling</td>
<td align="left">efficient wound repair</td>
<td align="left">
<xref ref-type="bibr" rid="B5">Chen et al. (2025)</xref>
</td>
</tr>
<tr>
<td align="left">Diabetic wound healing</td>
<td align="left">Photodetachable CNT-PC1Z2 scaffold</td>
<td align="left">Zn<sup>2&#x2b;</sup> release &#x2b; NIR antibacterial &#x2b; angiogenesis</td>
<td align="left">Diabetic rats: 98% antibacterial efficiency, faster closure</td>
<td align="left">
<xref ref-type="bibr" rid="B74">Wu et al. (2025)</xref>
</td>
</tr>
<tr>
<td align="left">Regenerative scaffolds</td>
<td align="left">CS/Gel/MWCNTs conductive scaffold</td>
<td align="left">Electrical stimulation&#x2192; fibroblast proliferation, collagen synthesis</td>
<td align="left">Enhanced tissue regeneration</td>
<td align="left">
<xref ref-type="bibr" rid="B35">Liu et al. (2025)</xref>
</td>
</tr>
<tr>
<td align="left">Regenerative scaffolds</td>
<td align="left">CNT-aligned nanofibrous sheet</td>
<td align="left">Provides directional keratinocyte migration</td>
<td align="left">Accelerated re-epithelialization</td>
<td align="left">
<xref ref-type="bibr" rid="B5">Chen et al. (2025)</xref>
</td>
</tr>
<tr>
<td align="left">Regenerative scaffolds</td>
<td align="left">superparamagnetic iron oxide nanoparticles/CNT/PVA/chitosan scaffold with Wharton&#x2019;s jelly stem cells</td>
<td align="left">Stem cell therapy &#x2b; MRI monitoring</td>
<td align="left">Burn wound repair &#x2b; stem cell tracking</td>
<td align="left">
<xref ref-type="bibr" rid="B18">Hashemi et al. (2025)</xref>
</td>
</tr>
<tr>
<td align="left">Regenerative scaffolds</td>
<td align="left">CNT&#x2013;cellulose supramolecular hydrogel</td>
<td align="left">Sustained drug release, antimicrobial, regenerative</td>
<td align="left">Multifunctional wound healing</td>
<td align="left">
<xref ref-type="bibr" rid="B12">Forero-Doria et al. (2020)</xref>
</td>
</tr>
<tr>
<td align="left">Regenerative scaffolds</td>
<td align="left">bacterial cellulose/polypyrrole/carbon nanotube</td>
<td align="left">Electroactive stimulation</td>
<td align="left">Enhanced fibroblast proliferation</td>
<td align="left">
<xref ref-type="bibr" rid="B68">Wang et al. (2020)</xref>
</td>
</tr>
<tr>
<td align="left">Smart dressings/sensors</td>
<td align="left">PVA/CNT-hydrogel bandage with glucose/pH sensors</td>
<td align="left">Real-time wound monitoring</td>
<td align="left">Non-invasive diabetic wound monitoring</td>
<td align="left">
<xref ref-type="bibr" rid="B23">Ji et al. (2025)</xref>
</td>
</tr>
<tr>
<td align="left">Smart dressings/sensors</td>
<td align="left">acellular dermal matrix/CNT &#x201c;E-skin&#x201d; scaffold</td>
<td align="left">Integrated therapeutic &#x2b; diagnostic</td>
<td align="left">Versatile wound bioelectronics</td>
<td align="left">
<xref ref-type="bibr" rid="B34">Liu et al. (2023)</xref>
</td>
</tr>
<tr>
<td align="left">Smart dressings/sensors</td>
<td align="left">CNT nanocomposite hydrogel</td>
<td align="left">Robust elasticity &#x2b; multifunctional sensing</td>
<td align="left">Wearable wound monitoring</td>
<td align="left">
<xref ref-type="bibr" rid="B59">Shen et al. (2023)</xref>
</td>
</tr>
<tr>
<td align="left">Smart dressings/sensors</td>
<td align="left">Thermoelectric CNT composite</td>
<td align="left">Thermoreceptor &#x2b; antibacterial</td>
<td align="left">Sensory dressing with antibacterial</td>
<td align="left">
<xref ref-type="bibr" rid="B61">Song et al. (2025)</xref>
</td>
</tr>
<tr>
<td align="left">Burn management</td>
<td align="left">thermally responsive PEG derivatives/CNT-hydrogel dressings</td>
<td align="left">Thermal conductivity &#x2b; heat storage</td>
<td align="left">Improved cooling in burn therapy</td>
<td align="left">
<xref ref-type="bibr" rid="B60">Shi et al. (2022)</xref>
</td>
</tr>
<tr>
<td align="left">Burn management</td>
<td align="left">CNT/gelatin methacryloyl macroporous nanocomposite hydrogels</td>
<td align="left">Antibacterial &#x2b; regenerative</td>
<td align="left">High-exudate wound healing</td>
<td align="left">
<xref ref-type="bibr" rid="B75">Xu et al. (2020)</xref>
</td>
</tr>
<tr>
<td align="left">Safety/biosafety</td>
<td align="left">CNT-fiber pulmonary model</td>
<td align="left">CNT&#x2013;fiber interaction, fibrosis modeling</td>
<td align="left">Long-term biosafety concerns</td>
<td align="left">
<xref ref-type="bibr" rid="B48">Pantzke et al. (2023)</xref>
</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
</body>
<back>
<sec sec-type="author-contributions" id="s9">
<title>Author contributions</title>
<p>NP: Writing &#x2013; original draft, Writing &#x2013; review and editing. KN: Conceptualization, Writing &#x2013; original draft, Writing &#x2013; review and editing. SK: Conceptualization, Investigation, Writing &#x2013; original draft, Writing &#x2013; review and editing.</p>
</sec>
<sec sec-type="COI-statement" id="s11">
<title>Conflict of interest</title>
<p>The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="ai-statement" id="s12">
<title>Generative AI statement</title>
<p>The author(s) declared that generative AI was used in the creation of this manuscript. Generative AI (ChatGPT, OpenAI) was used to assist with summarizing literature and drafting sections of the manuscript. All outputs were critically reviewed and edited by the authors to ensure accuracy and originality.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p>
</sec>
<sec sec-type="disclaimer" id="s13">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<fn-group>
<fn fn-type="custom" custom-type="edited-by">
<p>
<bold>Edited by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/896344/overview">Agnes Silvia Klar</ext-link>, University Children&#x2019;s Hospital Zurich, Switzerland</p>
</fn>
<fn fn-type="custom" custom-type="reviewed-by">
<p>
<bold>Reviewed by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1291604/overview">Elizabeth Igne Ferreira</ext-link>, University of S&#xe3;o Paulo, Brazil</p>
<p>
<ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1921169/overview">N. Raghavendra Naveen</ext-link>, Sri Adichunchanagiri College of Pharmacy, India</p>
</fn>
</fn-group>
<fn-group>
<fn fn-type="abbr" id="abbrev1">
<label>Abbreviations:</label>
<p>CNTs, Carbon nanotubes; SWCNTs, single-walled carbon nanotube; MWCNTs, multi-walled nanotubes; ECM, extracellular matrix; ROS, reactive oxygen species; NIR, near-infrared; AMPs, antimicrobial peptides; AgNPs, silver nanoparticles; ES, electrical stimulation; PNIPAM, poly(N-isopropylacrylamide); PVA, polyvinyl alcohol.</p>
</fn>
</fn-group>
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