Nanotopographical Features of Polymeric Nanocomposite Scaffolds for Tissue Engineering and Regenerative Medicine: A Review.

Nanotopography refers to the intricate surface characteristics of materials at the sub-micron (<1000 nm) and nanometer (<100 nm) scales. These topographical surface features significantly influence the physical, chemical, and biological properties of biomaterials, affecting their interactions with cells and surrounding tissues. The development of nanostructured surfaces of polymeric nanocomposites has garnered increasing attention in the fields of tissue engineering and regenerative medicine due to their ability to modulate cellular responses and enhance tissue regeneration. Various top-down and bottom-up techniques, including nanolithography, etching, deposition, laser ablation, template-assisted synthesis, and nanografting techniques, are employed to create structured surfaces on biomaterials. Additionally, nanotopographies can be fabricated using polymeric nanocomposites, with or without the integration of organic and inorganic nanomaterials, through advanced methods such as using electrospinning, layer-by-layer (LbL) assembly, sol-gel processing, in situ polymerization, 3D printing, template-assisted methods, and spin coating. The surface topography of polymeric nanocomposite scaffolds can be tailored through the incorporation of organic nanomaterials (e.g., chitosan, dextran, alginate, collagen, polydopamine, cellulose, polypyrrole) and inorganic nanomaterials (e.g., silver, gold, titania, silica, zirconia, iron oxide). The choice of fabrication technique depends on the desired surface features, material properties, and specific biomedical applications. Nanotopographical modifications on biomaterials' surface play a crucial role in regulating cell behavior, including adhesion, proliferation, differentiation, and migration, which are critical for tissue engineering and repair. For effective tissue regeneration, it is imperative that scaffolds closely mimic the native extracellular matrix (ECM), providing a mechanical framework and topographical cues that replicate matrix elasticity and nanoscale surface features. This ECM biomimicry is vital for responding to biochemical signaling cues, orchestrating cellular functions, metabolic processes, and subsequent tissue organization. The integration of nanotopography within scaffold matrices has emerged as a pivotal regulator in the development of next-generation biomaterials designed to regulate cellular responses for enhanced tissue repair and organization. Additionally, these scaffolds with specific surface topographies, such as grooves (linear channels that guide cell alignment), pillars (protrusions), holes/pits/dots (depressions), fibrous structures (mimicking ECM fibers), and tubular arrays (array of tubular structures), are crucial for regulating cell behavior and promoting tissue repair. This review presents recent advances in the fabrication methodologies used to engineer nanotopographical microenvironments in polymeric nanocomposite tissue scaffolds through the incorporation of nanomaterials and biomolecular functionalization. Furthermore, it discusses how these modifications influence cellular interactions and tissue regeneration. Finally, the review highlights the challenges and future perspectives in nanomaterial-mediated fabrication of nanotopographical polymeric scaffolds for tissue engineering and regenerative medicine.