Carbon nanofibers have emerged as a promising material for biocompatible scaffolds due to their unique combination of mechanical strength, electrical conductivity, and structural adaptability. These properties make them particularly suitable for applications in neural and cardiac tissue regeneration, where electrical signaling and mechanical support are critical. The fabrication of carbon nanofiber scaffolds primarily involves electrospinning and 3D printing techniques, each offering distinct advantages in terms of porosity, fiber alignment, and scalability.

Electrospinning is the most widely used method for producing carbon nanofiber scaffolds. The process involves the application of a high-voltage electric field to a polymer solution, which is then drawn into fine fibers collected on a grounded substrate. Precursors such as polyacrylonitrile (PAN) are commonly used, followed by stabilization and carbonization to convert the polymer fibers into carbon nanofibers. The diameter of the fibers can be controlled by adjusting parameters like solution viscosity, voltage, and flow rate, typically ranging from 50 to 500 nanometers. Electrospun carbon nanofiber scaffolds exhibit high porosity, often exceeding 80%, which facilitates cell infiltration and nutrient diffusion. The random or aligned orientation of fibers can be tailored to mimic the anisotropic structure of tissues like cardiac muscle or peripheral nerves.

3D printing offers another route for fabricating carbon nanofiber scaffolds with precise architectural control. Techniques such as fused deposition modeling (FDM) or direct ink writing can incorporate carbon nanofibers into biocompatible polymers like polylactic acid (PLA) or polycaprolactone (PCL). The resulting scaffolds exhibit interconnected pores with tunable sizes, typically between 100 and 500 micrometers, which are critical for vascularization in thick tissue constructs. Unlike electrospinning, 3D printing allows for the creation of complex geometries, such as gradient porosity or hierarchical structures, to better match the mechanical and biological requirements of the target tissue.

Porosity is a key factor in scaffold performance, influencing cell adhesion, proliferation, and extracellular matrix deposition. Carbon nanofiber scaffolds excel in this regard due to their inherent fibrous network, which provides a high surface area-to-volume ratio. Studies have shown that pore sizes between 20 and 150 micrometers are optimal for most cell types, including cardiomyocytes and neurons. The open-pore structure also ensures efficient waste removal and oxygen transport, critical for maintaining cell viability in vitro and in vivo.

Mechanical compatibility with native tissues is another advantage of carbon nanofiber scaffolds. The Young’s modulus of carbon nanofibers ranges from 10 to 50 GPa, which can be modulated by adjusting the carbonization temperature or blending with softer polymers. For cardiac tissue engineering, scaffolds with a modulus matching that of heart muscle (10–50 kPa) have been developed by incorporating elastomeric components. Similarly, neural scaffolds often require a balance between stiffness for structural support and flexibility to avoid damaging delicate axons.

The electrical conductivity of carbon nanofibers sets them apart from many other scaffold materials. With conductivities ranging from 1 to 100 S/cm, these scaffolds can facilitate electrical signal propagation in excitable tissues. In cardiac applications, carbon nanofiber scaffolds have been shown to enhance the synchronization of cardiomyocyte contractions, improving the functional outcomes of engineered tissues. For neural regeneration, conductive scaffolds promote neurite outgrowth and synaptic activity, as demonstrated in studies using dorsal root ganglion cells. The ability to support electrical stimulation without the need for external electrodes is a significant advantage over insulating polymer scaffolds.

Despite these benefits, cytotoxicity and biodegradability remain important considerations. Pure carbon nanofibers are generally considered biocompatible, with minimal inflammatory responses reported in vivo. However, residual metal catalysts or organic solvents from fabrication processes can pose risks. Thorough purification and surface modifications, such as oxidation or coating with bioactive molecules, can mitigate these issues. Biodegradability is limited in carbon nanofibers due to their crystalline structure, but hybrid scaffolds incorporating degradable polymers can provide temporary support while allowing gradual tissue integration.

Carbon nanofiber scaffolds differ from carbon nanotube (CNT) or graphene-based scaffolds in several ways. While CNTs offer higher conductivity and mechanical strength, their tendency to aggregate and potential toxicity due to high aspect ratios have raised concerns. Graphene scaffolds, on the other hand, provide excellent surface chemistry for cell adhesion but lack the fibrous morphology that promotes cell alignment and migration. Carbon nanofibers strike a balance, offering manageable toxicity, ease of processing, and structural similarity to the extracellular matrix.

In summary, carbon nanofiber scaffolds represent a versatile platform for tissue engineering, particularly in applications requiring electrical conductivity and mechanical support. Advances in fabrication techniques like electrospinning and 3D printing have enabled precise control over porosity and architecture, while ongoing research addresses challenges related to cytotoxicity and biodegradability. Compared to other carbon-based materials, carbon nanofibers offer a favorable combination of properties, making them a promising candidate for regenerative medicine.