Table 1 A summary of the features and construction methods of conduits used in peripheral nerve repair
Item | Descriptions | Advantages | Disadvantages | |
|---|---|---|---|---|
Biological conduits | • These conduits typically consist of vessels, muscles (muscle fibers), amniotic membrane, biological membranes, fats, and nerve trunks • The decellularization approach (physical, chemical, and enzymatic) is essential to minimize graft rejection when using allogeneic or xenogeneic biological conduits | Unlimited supply, reduced surgical time, high biodegradability and bio-absorption, natural topological structures and patterns, improved cell functions such as adhesion, proliferation, differentiation, and development | Unfavorable in long nerve transections, immunogenicity enhancement, rapid destruction, disease transmission, adverse structural changes during processing, ethical concerns, need to pharmacological suppressors, diverse cellular responses, and long manufacturing processes | |
Polymeric conduits | Natural | • The most significant natural polymers are chitosan, silk fibroin, collagen, alginate, gelatin, and hyaluronic, which collagen has garnered the most attention • Asymmetric degradation of natural polymers suggests that the resulting conduits should be less than 15 mm in length | High biodegradability and biocompatibility, coming from renewable sources, simple and cheap generation, high biological absorption, high permeability and porosity during repair, reducing inflammation in most cases, high cell adhesion, and strengthening angiogenesis | Variable mechanical properties with a low Young’s modulus, thermal and mechanical limitations in conduit production, low process ability asymmetric destruction, rapid decomposition in pH < 7, potential transmission of viral or bacterial, and heterogeneous chemical and physical structures |
Synthetic | • Among the wide range of synthesized polymer compounds, the most crucial ones for nerve repair activities are PLA, PGA, PCL, PLGA, PLLA, and PDMS • Complete compliance of synthetic polymer-based conduits with the nerve recovery period (3–6 months) due to the delay in degradation | High mechanical properties (strength, elasticity, flexibility), high thermal or chemical stability, acceptable performance in all gaps, excellent plasticity, controlled biodegradability, abundant resources, relatively simple production, chemical uniformity of structures | Weak cell adhesion, relatively high immunogenicity, limited bioactivity, poor biocompatibility, ischemia of nearby tissues, decreased angiogenesis, limited reproducibility, acidic byproducts, and low process ability | |
Non organic conduits | • The most important inorganic compounds in nerve tissue regeneration are silicone hydrogels and carbon compounds | High thermal or electrical conductivity, anti-bacterial, very elastic (up to ~ 18%) elongation, high tensile strength, and flexibility | High toxicity, impurities, blood clotting, immunogenicity, and long-term stability in nerve tissue | |
Printing methods | Extrusion | • Extrusion printing defined with injecting a molten thermoplastic polymer filament through a heated nozzle onto the printing surface • The nozzle moves in the x, y and z directions according to software instructions, and the extruded materials are injected by pneumatic pressure | Cost-effectiveness, good mechanical properties, high commercial availability, wide range of biomaterials, excellent performance with various cell types, minimal cell damage compared to other techniques, rapid conduit production, low extrusion temperature, and shape versatility | Limited filament clarity (typically over 100 µm) with minimal surface detail, increased risk of layer falling, abnormal fusion of initial layers, relatively low strength, weak end layers bonding, requirement for material of viscose, and restricted to thermoplastic materials |
Inkjet | • In this system, fine droplets of polymer solution are deposited along the x, y, and z axes to create a pattern on the substrate • To produce bio-ink droplets, it uses piezoelectric pulses (by sound waves) and thermal pulses (by electric heat) | Good resolution of 50 to 75 µm, ability to print with pL volume droplets, minimal thermal effects, no contact between nozzle and conduit, rapid gelation, high operational capability, heterogeneous multicell capability, and cell viability of over 85% | Restricted to low-viscosity materials, uncertainty cell encapsulation, clogging at high viscosity, limitations in cell density, relatively subpar mechanical properties, atypical droplet dryness, height restrictions, challenges in 3D geometry, and longtime manufacturing | |
Laser | • Using a laser source to create scaffolds on substrates, which is done through laser-guided direct writing or laser-induced forward transfer • This process involves a focusing system (for alignment), a ribbon, a pulsed laser beam (for efficient transmission), and a substrate | The use of bio-ink with high viscosity, a wide range of materials, a high concentration of cells, and a system that prevents nozzle blockage, allows for fine shaping, excellent arrangement of cell patterns, high cell viability, accuracy, and rapid gelation | Longtime printing, elevated thermal impact, increased expenses, diminished mechanical resilience, and aggregation at the final construct | |
Stereo-lithography | • This technology employs a light source, such as ultraviolet or infrared with a light-sensitive resin, to produce 3D structures | Highly accurate 3D shapes, and simple removal of material trapped in the scaffold | Consumable materials limitation based on photo response, high toxicity of resins, and high production cost | |
Textile engineering methods | Electrospinning | • Electrospinning has the characteristics of electrospraying and dry spinning • The polymer solution is injected by a low-speed syringe pump into an external electrostatic field and then collected on the collector | Simple production process, scalable, structure similar to extracellular matrix, cheap, scalable, ability to produce nanometer to micrometer fibers in one structure, high porosity, and high surface to volume ratio | Use of toxic solvents, insufficient cell filtration, asymmetric cell distribution, injection instability, non-repeating structures, the effect of environmental and voltage on the structure, and high energy consumption |
Other technology | • Woven, knitting, and braiding technologies are the primary methods used in the textile field to fabricate conduits • The potential for creating conduits layer by layer according to nerve repair requirements | High bionic surface morphology, flexible, suitable mechanical connections, low cost, easy technique, rapid production of conduits with similar size and shape, mechanical strength and pore size scalable, high cell adhesion and migration | Limited diameter of woven conduits, improper increase of wall thickness of conduits, expensive software and hardware package for adjusting the weaves direction | |
Decellularization methods | Physical | • Biological tubes are decellularized using freezing, hydrostatic pressure, electric currents, mechanical shocks, gamma radiation, and supercritical fluids to produce conduits | Facilitated decellularization, minimal immunogenicity, low cost, potential for commercialization | Destruction of tubular structure, low efficiency of cell removal in dense tissues, and unfavorable compaction of ECM |
Enzymatic | • Collagenase, trypsin, galactosidase, nuclease, and pepsin are enzymes that remove tissue and cell debris, often considered as an auxiliary process | Cell membrane digestion, complete elimination of antigenic and genomic compounds, no impact on ECM, and targeted removal of specific compounds | Long-term presence has a negative effect on ECM and cell membrane, complex washing, long process with undetermined time, possible immunogenicity with enzyme retention, changes in protein microstructures | |
Chemical | • Direct removal of cells by washing in chemical agents such as acids (peracetic acid, H2SO4, etc.), alkalis (NH4OH, NaOH), EDTA, TnBP, SDS, ethylene oxide and acetone: ethanol, Triton X-100 | Highly efficient cell removal with minimal genomic residues, preservation of tubular structure, optimal preservation of ECM structure (collagen, elastin, proteoglycans, etc.) based on the type of chemical agent, and preservation of binding factors | Challenges vary depending on the type of chemical agent, including collagen and glycosaminoglycan degradation by SDS, low cell removal efficiency with Triton X-100, low cell removal efficiency with EDTA, and toxicity of chemical agents | |