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Table 3 A summary of the pros and cons of methods for creating micro- or nano-patterns to regenerate nerve tissue [1, 9, 37, 68]

From: Recent advances in enhances peripheral nerve orientation: the synergy of micro or nano patterns with therapeutic tactics

Structure

Manufacturing method

Benefits

Drawbacks

Fiber

Extrusion, phase separation, drawing, spinning (solution, electro, centrifuge, melting, gel, wet/dry),

texturing, molding, printing

Similar to ECM in structure, wide range of materials, inducing cell orientation and directional growth of neurite/axons with fiber alignment, easy modification of fiber diameter, low cost, high porosity, easy implementation, diverse designs, simple surface modification, and quick access of cells to loaded materials

In aligned fibers: low mechanical strength, time-consuming production, increased structural collapse, increased cell migration, low cell adhesion

In random fibers: low cell infiltration, calling of M1 type macrophages, low cell affinity, uncontrollable morphology and cavities

Channel

Lithography, printing, molding, freeze drying, solvent leaching, thermal-induced phase separation, electrospinning

High cell migration to depth, high cell orientation and directional growth of neurites/axons, controlling the invasion of adjacent tissues, reducing scars, simulating fascicles, controlling neuroma or nerve coils, high loading of neurotrophic factors, increasing the connection of two nerve ends

Reducing the penetration of signals and vital environmental secretions, unusual blockage of channels, complex production, reducing the diameter of fibers, lack of structural connection and signal between adjacent fibers

Groove

Lithography, molding, laser ablation, solvent casting, ion etching, electrospinning,

Mimic native tissues, high cell migration to depth, high cell orientation, manipulation of directional growth of neurite/axon, strengthening the high adhesion of cells, High variability of shape and size of grooves/edges in one platform

Complex production, accumulation of dirt/dust in between the groove, limited control on surface chemistry, stamp distortion, cell response dependent on groove/ridge size

Pillar

Lithography, molding, electron beam and hot embossing

High ability in promoting neurite growth, precise control over pillar placement, manipulation of neurite growth angles through pillar shape modification, enhanced cell adhesion, simulation of 3D culture, minimized cell death through optimal nutrient and waste flow

Complex design and long-time production, high costs, limitations on pillar height, resource constraints, poor substrate recovery, limited control over neurite growth location, reduced cell migration capacity, and poor cell orientation

Pit

Molding and solvent casting

Simple production, wide range of pit shapes and sizes, high flow rate of biological materials, extensive storage of compounds and medications, reinforcement of adhesion surface particularly in non-spherical edges, high flexibility

The risk of solvents, blockage of some pits, low cell orientation, poor directional growth of neurites/axons, presence of mega-pits