**Background:** Tissue engineering relies on scaffolds that provide a temporary extracellular matrix for cell adhesion, growth, and tissue formation. Ideal scaffolds require mechanical strength, biocompatibility, controlled degradation, and the ability to support cell proliferation. Traditional fabrication methods (freeze-drying, phase separation, gas foaming) often fail to mimic native tissue structure. 3D bioprinting offers precise control over scaffold geometry and microstructure, while nanotechnology enables materials to guide cell activity at the cellular and subcellular levels. This review synthesizes the convergence of these two fields.
**Methods:** The authors conducted a narrative review of the literature on 3D bioprinting and nanotechnology in tissue engineering scaffolds. They categorized scaffold materials into natural polymers (chitosan, cellulose, alginate, collagen, dextran), synthetic polymers (PLA, PLGA, PCL, PU, PVA), and polymer derivatives (chitosan derivatives, cellulose derivatives, gelatin derivatives). For each material class, they summarized studies incorporating nanomaterials (e.g., nano-hydroxyapatite, nanocellulose, carbon nanotubes, gold nanoparticles, iron oxide nanoparticles) to enhance scaffold properties. Four 3D bioprinting technologies were reviewed: inkjet-based, extrusion-based (including FDM, melt electrowriting, near-field electrospinning), laser-assisted, and stereolithography bioprinting. Applications in bone, neural, vascular, tendon, and organ tissue engineering were discussed.
**Key Results:** The review presents numerous examples of nanomaterial-enhanced scaffolds. For bone tissue, Yu et al. blended hydroxyapatite nanocrystals with poly(ester urea) via FDM to create scaffolds with 75% porosity and mechanical properties of 65–85 MPa; calcium concentration in mineralized ECM increased 185-fold after four weeks. For neural tissue, Lee et al. combined multi-walled carbon nanotubes with PEGDA using stereolithography (355 nm laser) to fabricate scaffolds that promoted neural stem cell proliferation and neuronal differentiation under biphasic pulse stimulation at 500 μA. For vascular tissue, Miao et al. used VEGF-modified black phosphorus nanosheets in a DNA hydrogel integrated with 3D-printed PCL scaffolds, doubling HUVEC tube formation compared to constructs without VEGF. For tendon tissue, Yang et al. arranged oriented PCL nanofiber yarns by dry-wet electrospinning, which induced tendon orientation and elongation in rat tendon repair models. For cardiac tissue, Lei et al. fabricated multi-scale micro/nanofiber conductive scaffolds with layer-specific fiber orientation using electrohydrodynamic printing, enhancing expression of cardiac-specific genes. In extrusion-based printing, Naghieh et al. found that PLA/gelatin forsterite scaffolds showed approximately 52% higher elastic modulus than pure PLA scaffolds. Chen et al. reported that adding graphene oxide to TPU/PLA nanocomposites improved compressive modulus by 167% and tensile modulus by 75.5%. For ink properties, Sadeghianmaryan et al. showed that nano-hydroxyapatite increased elastic modulus of chitosan/sodium alginate scaffolds and enhanced cell viability. Xu et al. demonstrated that 3D-printed nanocellulose hydrogels could tune mechanical strength in the 3–8 kPa range, with increased stiffness promoting cell proliferation.
**Clinical Implications:** The convergence of 3D bioprinting and nanotechnology offers clinically relevant advantages: enhanced mechanical properties matching native tissues, improved bioactivity through nanomaterial-cell interactions, and the ability to create patient-specific scaffold geometries. Applications in bone repair (nano-hydroxyapatite composites), nerve regeneration (carbon nanotube scaffolds), vascularized tissue constructs (VEGF-delivering nanosheets), and tendon repair (aligned nanofiber yarns) show preclinical promise. However, the authors note that the highest printing resolution reaches the micro range but is insufficient for capillary-level structures, and scaffolds combining cells and growth factors face storage challenges due to low activity and instability. Spatiotemporal control of 3D cell distribution in large scaffolds remains limited, constraining applications in complex organs like kidney and liver.