Abstract
Carbon materials have emerged as a rapidly advancing category of high-performance materials that have garnered significant attention across various scientific and technological disciplines. Their exceptional biochemical properties render them highly suitable for diverse biomedical applications, including implantation, artificial joints, bioimaging, tissue and bone engineering, and scaffold fabrication. However, a more systematic approach is required to fully exploit the potential of carbon-based materials in the biomedical realm, necessitating extensive and collaborative research to address the existing challenges, which comprehensive long-term stability studies, the surface properties and investigate the toxicity of biomedical materials. This review paper aims to provide a comprehensive overview of carbon materials, elucidating their inherent advantages and highlighting their increasingly prominent role in biomedical applications. After a brief introduction of carbonaceous materials, we discuss innovative deposition strategies that can be utilized to artificially replicate desired properties, such as biocompatibility and toxicology, within complex structures. Further, this paper serves as a valuable resource to harness the potential of carbon materials in the realm of biomedical applications. Last, we conclude with a discussion on the significance of continuous exploration in propelling further advancements within this captivating field.
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1 Introduction
In recent years, significant progress has occurred in the field of biomedical materials and technologies, establishing a robust foundation for forthcoming advancements and practical applications [1, 2]. Within the expanding landscape of academic inquiry, carbon-based materials, including carbon dots, carbon nanotubes (CNTs), graphene, carbon nanofibers (CNFs), and MXenes, have emerged as key focal points, presenting themselves as promising candidates for future material design and utilization [3].
Carbon dots, characterized as zero-dimensional (0D) materials with singular domains of small size (typically 1 to 30 nm in diameter), have garnered significant attention due to their low toxicity, facile surface functionalization, diverse raw material sources, cost-effectiveness, excellent fluorescence stability, adjustable emission wavelength, and biocompatibility [4,5,13,14,15].
Graphene consists of single-atom-thick sheets of sp2-bonded carbon atoms closely packed into a 2D honeycomb lattice. Graphene and its derivatives, such as graphene oxide (GO) and reduced graphene oxide (rGO), exhibit unique properties including large surface area, strong laser absorption property, high elasticity, good charge-transfer ability, and ferromagnetic properties [16,17,18,19]. In addition, graphene’s excellent electrical conductivity makes it an ideal material for biosensors. Functionalized graphene can be employed to detect specific biomolecules with high sensitivity, enabling early diagnosis of diseases. GO also serves as contrast agents in various imaging techniques, including magnetic resonance imaging (MRI) and photoacoustic imaging, providing enhanced contrast for more accurate diagnostics [20, 21].
CNFs are nanoscale materials characterized by a fibrous structure primarily composed of carbon atoms. Their extensive application as reinforcing elements in tissue engineering scaffolds is attributed to their impressive mechanical strength, electrical conductivity, and structural integrity. This utilization enhances cell adhesion and contributes to the regeneration of tissues, exemplified in applications like artificial teeth and hip joints. In these contexts, CNFs are progressively supplanting metal materials, addressing concerns such as corrosion and diminished impact resistance associated with traditional metals [22,23,24,25,26,27,28].
MXenes are a unique class of 2D materials comprised of transition metal carbides, nitrides, or carbonitrides with a general formula of Mn+1Xn (n = 1–3), where “M” represents an early transition metal and “X” denotes carbon or nitrogen. This combination of complete metal atomic layers and abundant surface functional groups enables MXenes to possess both metallic conductivity and hydrophilic properties [29,30,31]. These materials exhibit a thickness of less than 1 nm due to their limited number of atomic layers. Their nanoscale size allows for prolonged circulation within biological systems while also introducing unique characteristics, such as enhanced molecular interactions and size-dependent luminescence [32,33,34]. MXenes present promising possibilities for highly sensitive disease diagnosis and efficient treatment.
Distinguished by their unique attributes, the burgeoning interest in carbon-based materials as reinforcements for biomedical applications has been rapidly growing, positioning them particularly well for pivotal roles in various biomedical applications. Notably, carbon materials display a reduced propensity for eliciting immune responses compared to alternative materials, such as metal nanoparticles—a critical feature for sustained biological interactions, especially in the realm of implantable organ devices [35,36,37,38].
Moreover, carbon-based materials and their hybrid metal/polymer/ceramic nanocomposites demonstrate significant potential across a broad spectrum of biomedical applications. The collaborative interaction among these constituents establishes a synergistic relationship, augmenting the overall strength of the produced nanocomposites. Carbon-based materials assume a pivotal role in enhancing the chemical and mechanical properties of the hybrid nanocomposites, capitalizing on their diminutive size, expansive surface area, and surface modification capabilities. The polymer matrix serves the crucial function of maintaining an optimal distance between the carbon materials, preventing agglomeration. Concurrently, the amalgamation of ceramics with carbon materials facilitates the concurrent existence of photoluminescence and magnetic properties, contributing to wear resistance and dispersion control. Simultaneously, metal nanoparticles enhance the mechanical properties, thermal stability, and electrical conductivity within the hybrid nanocomposites. This precise control at the nanoscale renders them versatile for specific and sophisticated biomedical applications, such as highly controlled drug delivery systems, tissue engineering, medical imaging, implant coatings, diagnostic tools, and biosensors [39, 40]. An exemplary illustration of their capabilities lies in advanced designs enabling precise drug transport to targeted areas within the body, thereby enhancing efficacy, minimizing side effects, and enabling controlled release—a transformative paradigm in disease treatment. These adaptable materials manifest in various formats, including films, nanofibers, hydrogels, and 3D porous structures, extending their utility across a diverse range of biomedical applications [41, 42].
However, certain nanoparticles, such as CNTs and MXenes, continue to pose challenges due to their inherent toxicity. Overcoming these challenges necessitates precise functionalization, sophisticated dispersion methods, or targeted modifications aligned with specific biomedical goals. Various techniques, such as electrospinning, microsphere fabrication, nanocomposite synthesis, hydrogel formulation, deposition coating, and 3D printing, have also been widely acknowledged for their potential in augmenting biomedical applications. Furthermore, strict adherence to preclinical safety pharmacology guidelines set forth by regulatory bodies such as the Food and Drug Administration (FDA), the International Conference on Harmonization (ICH), and the European Medicines Agency (EMA) is imperative [43,44,45,46,47,48, Carbon-based materials and their composites hold remarkable promise across various biomedical domains, owing to their exceptional attributes. These include substantial specific surface areas, high hydrophilicity, adaptable layer thickness, modifiable structures, and a diverse range of compositions. Notably, carbon-based materials, such as graphene quantum dots, exhibit an impressive level of biocompatibility, minimizing undesirable reactions when interfacing with biological systems. Their noteworthy surface area-to-volume ratio facilitates efficient drug delivery, thus amplifying therapeutic effectiveness. Furthermore, the exceptional electrical conductivity inherent to carbon materials empowers the development of bioelectrodes and biosensors, enabling precise monitoring of physiological parameters. Additionally, the tunable mechanical properties of carbon-based materials render them highly suitable for an array of applications, including implants, artificial joints, bone engineering, and scaffold reinforcement. Notwithstanding the advantages, it is crucial to recognize that the adoption of carbon materials in biomedical applications necessitates comprehensive long-term stability studies to ensure their reliability and safety—substantial research has been conducted but this field is still in its early stages. Looking ahead for these carbon-based materials and coating techniques in biomedical applications, the future direction encompasses a multifaceted approach. It begins with the imperative of conducting comprehensive, long-term, in vivo safety assessments to ensure the sustained well-being of patients. Simultaneously, the focus extends to innovation, with a goal to develop multifunctional materials, such as hybrid metal/polymer/ceramic nanocomposites, that transcend conventional roles and offer versatile solutions in diagnostics and therapeutics. In this context, a meticulous understanding of surface properties through detailed characterization is emphasized, aiming to tailor materials for specific biomedical applications, optimize performance, and predict biological responses accurately. Also, establishing industry standards emerges as a pivotal step, involving the definition and implementation of guidelines governing manufacturing processes, quality control, and safety protocols. Collectively, this comprehensive strategy seeks to advance the field, ensuring the responsible and effective utilization of carbon-based materials in the evolving landscape of biomedical science. Comprehensive long-term stability studies are urgently needed for emerging carbon-based materials. For instance, MXenes, which have garnered substantial attention for potential biomedical applications, exhibit initial signs of low toxicity. However, a systematic exploration of their toxicity, environmental impact, and effects on human health is lacking, leaving the underlying mechanisms unclear. To fully harness the potential of MXenes in biomedicine, addressing these challenges through further research is imperative. Although extensive research has probed the safety of carbon-based materials, it is essential to acknowledge that many biocompatibility studies have relatively short durations compared to human lifespans. To obtain a comprehensive understanding of long-term effects, in-depth and extended studies focusing on biocompatibility and toxicity are imperative for accurately evaluating the safety and potential risks associated with the biomedical use of carbon-based materials. From these, a robust assessment of long-term biocompatibility and toxicity profiles can be achieved, offering vital insights for the development of safe and effective biomedical materials and devices. The characterization and comprehension of surface properties in carbon-based materials remain domains necessitating extensive investigation. Specifically, there is a pressing requirement for a systematic exploration of how surface properties influence the stability of carbon-based materials in aqueous solutions and comprehensive studies on surface modification techniques. These inquiries are pivotal in facilitating the expansion of carbon-based materials’ applications by providing heightened control over their surface attributes. Notably, within the context of medical markers, proficient surface engineering holds the potential to significantly enhance their performance. Securing the effective functionality and stability of biomedical coatings mandates a thorough and prolonged biotribological evaluation. The substantial threat posed to the performance of coatings by wear and degradation, exacerbated by the absence of replenishment mechanisms, has constrained the range of applicable coatings. To address this challenge, the application of accelerated wear testing methods facilitates the simulation of extended usage within a condensed timeframe. Researchers employ multi-modal characterization techniques for a thorough assessment of coating surfaces over time, alongside long-term in vivo studies that allow the observation of materials’ performance within living organisms. Integration of smart sensors facilitates continuous monitoring of factors like friction and wear. Furthermore, real-time insights into the wear and degradation of biomedical coatings are gained through continuous monitoring and data collection systems. This multifaceted approach contributes to a nuanced understanding of the long-term behavior and performance of biomedical materials. The establishment of carbon-based materials for biomedical applications relevant to clinical and industry standards emerges as a pivotal imperative. The significance of this endeavor lies in its capacity to ensure consistency, safety, and efficacy across diverse applications. Standardization not only fosters regulatory compliance but also engenders a framework for rigorous evaluation, comparability, and interoperability within the realm of biomedical technologies. By delineating clear and comprehensive standards, the biomedical community can navigate the challenges associated with the integration of carbon-based materials, fostering advancements that are not only scientifically robust but also ethically and clinically sound. Standardization efforts are poised to facilitate the seamless translation of research innovations into clinical practice, thereby promoting the reliability and reproducibility of outcomes in the biomedical applications. This review offers a comprehensive exploration of carbon materials, emphasizing their growing significance in biomedicine and innovative deposition techniques to attain specific properties. Additionally, we scrutinized various products employing carbon-based composites. While the widespread adoption of carbon materials in biomedical applications is still in its early commercial stages, noteworthy successes have been witnessed in products like carbon fiber wound dressings. Therefore, a profound understanding of the unique properties of diverse carbon materials and their strategic integration within the biomedical sector holds the potential to unlock further advancements in tailored biomedical solutions. These attributes underscore the diverse advantages of carbon materials in advancing biomedical technologies.5 Summary and future directions
Data availability
All data included in this study are available from the corresponding author (Soo-** Park), upon reasonable request.
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This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2022M3J7A1062940).
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Choong-Hee Kim: writing-original draft; Seul-Yi Lee: writing—review and editing; Kyong Yop Rhee: supervision, project administration; Soo-** Park: supervision, project administration, writing—review and editing.
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Kim, CH., Lee, SY., Rhee, K.Y. et al. Carbon-based composites in biomedical applications: a comprehensive review of properties, applications, and future directions. Adv Compos Hybrid Mater 7, 55 (2024). https://doi.org/10.1007/s42114-024-00846-1
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DOI: https://doi.org/10.1007/s42114-024-00846-1