Table 3.

Studies evaluating NGC porosity, and size of pores.

Study	Type of Study	Material	Technique	Porosity, Size or Distribution of Pores	Main Outcome
Oh et al., 2007 [43]	Pre-experimental study of biomaterials development	Poly(lactic-co-glycolic acid) PLGA and Pluronic F127	Modified immersion precipitation	Inner tube surface: nano-pores ~50 nm/Outer tube surface: micropores ~50 μm	PLGA/F127 tube (3 wt%): optimal mechanical properties and hydrophilicity. Highly effective for nutrient permeability. The tubes show a decrease in mechanical resistance with an increase in the Pluronic F127 compositions.
Kokai et al., 2009 [44]	Pre-experimental study of biomaterials development	Poly(caprolactone) (PCL)	Dip-coating/ salt-leaching technique	Wall thickness: 0.2, 0.6 mm Porosities: 50, 80% Pore size:10–38; 75–150 μm	NGC (0.6 mm) decreased lysozyme loss (~10%) without diminishing glucose permeability. Low porosity NGC (50% porous) showed smooth inner walls and several blind-ended or closed pores. High porosity NGC (80%) showed fewer smooth walls with highly interconnected through-pores for transluminal flow and solute diffusion. NGC (0.6 mm; 10–38 μm pores, 50% porous) were almost impermeable for glucose and lysozyme.
Pawelec et al., 2019 [45]	Pre-experimental study of biomaterials development	Poly(lactide co-glycolide) (PLGA) Poly(caprolactone) (PCL)	Polymer and salt slurry	Relative density of porous films 70 vol% porosity and non-porous films Wall thickness: 61.5–150 µm	Porosity in the scaffold increased compliance from 0.05 ± 0.1 in non-porous PCL to 1.75 ± 0.2 in porous PCL. Porosity decreased flexural stiffness (×10−2 N / mm) from 57.40 ± 16.0 in non-porous PCL to 0.88 ± 0.4 in non-porous. In addition, the porous PLGA scaffolds were approximately 30 times stiffer than the porous PCL with higher deformation. On the other hand, the deformation behavior of the scaffolds depended to a great extent on the material. Porous PCL scaffolds exhibited less than 30% permanent deformation after compression. In contrast, the porous PLGA scaffolds experienced a deformation of more than 45%.
Kim et al., 2016 [4]	In vitro: PC12 and S42 cells	Poly lactic-co-glycolic acid (PLGA) and polyurethane (PU)	Electrospinning	Highly-aligned nanofibers and randomly-oriented nanofibers on a single mat with nano to micro sized pores (50 nm–5 μm)	The average diameter of the pores in the aligned nanofibrous mat is three times larger than that in the randomly-oriented mat. The porosity of the aligned nanofibrous scaffolds was higher. Aligned nanofibers served as a guide for neural cells and were able to achieve a higher cell proliferation and migration compared to randomly oriented nanofibers.
Ghorbani et al., 2017 [46]	In vitro: L929 fibroblast cells	Poly (lactic-co-glycolic acid) (PLGA)	Freeze-drying and freeze-cast molding method	Porosity (%): 96.33 or 96.16 Pore size (μm): 111.32 ± 160.2; 138.93 ± 302.6 and 152.71 ± 679.9	Randomly oriented pore (freeze-dried) and interconnected pore (freeze-cast) NGC stimulate ECM to support cellular adhesion and migration. Different NGC manufacturing processes affect their properties by altering the microstructure of pores.
Huang et al., 2018 [47]	In vitro: DRG cells cultures	Poly(ε-caprolactone) (PCL) sheaths and collagen-chitosan (O-CCH) filler.	Electrospinning	Pores size: 6.5 ± 3.3 μm Wall thickness: 100, 200, 400 μm	NGC (100 µm) collapsed without additional force. NGC (200 µm) provided a strength lower than 0.02 N/mm at a lateral displacement of 0.3 mm. NGC (400 µm) provided a strength of 0.05–0.065 N/mm at a lateral displacement of 0.3 mm, comparable to commercially available NGC. A PCL porous sheath (pore size: 6.52 ± 3.28 μm) prevented fibroblast invasion and provided mechanical strength for fixation and resistance to compression, exhibiting the appropriate porosity to ensure the supply of oxygen and nutrients, also preventing fibrous tissue infiltration.
Vijayavenkataraman et al., 2018 [48]	In vitro: PC12 cells	Poly(ε-caprolactone) (PCL)	Electrohydrodynamic jet 3D printing (EHD-jetting)	Different pore sizes scaffolds (125–550 μm) and porosities (65–88%).	The Young’s modulus of the NGC structure decreases with increasing pore size from 275 ± 13 to 121 ± 16 MPa. Similarly, the yield stress also has a decreasing trend with increasing pore size from 24 ± 3 to 5.6 ± 2 MPa. The ultimate strength of the structure decreases from 32 ± 2.4 to 9 ± 1.4 MPa. Desirable NGC structure was observed to have 125 ± 15 μm pores. Porosity over 60%: Mechanical properties closer to the native peripheral nerves, and an optimal degradation rate in nerve regeneration post-injury. The percentage decrease of the mechanical properties from day 0 to day 28 was greater in the scaffolds with a greater pore size (550 μm) (~30 to 66%) and was the least in scaffolds with a smaller pore size (125 μm) (~22–45%).
Chan et al., 2007 [13]	In vitro: SC and fibroblasts In vivo: Sciatic nerve of Sprague–Dawley rats	Poly(DL-lactic acid-co-glycolic acid) (PLGA)	Immersion–precipitation phase inversion using a casting process	Asymmetric conduits with: high-porosity (permeability) 83.5 ± 5.3%; Medium-porosity (high outflow and low inflow) 73.6 ± 4.7 %; Low-porosity (permeability) 66.1 ± 3.4%.	NGC with different porosities prevented fibrous scar tissue invasion. Allowing the permeation of nutrients, oxygen, and proliferation of SC. Patent directional NGC showed more type A and B myelin fibers in the middle duct and distal nerve compared to the high bidirectional patency NGC.
Chang et al., 2006 [49]	In vivo: sciatic nerve defects in Sprague–Dawley rats (n = 80).	Poly(DL-lactic acid-co-glycolic acid) (PLGA)	Immersion–precipitation phase inversion using a casting process	NGC: Asymmetric: macrovoids (outer layer), and interconnected micropores (inner layer), possessed characters of larger outflow rate than inflow rate. Autografts Silicone Non-asymmetric	Asymmetric PLGA NGC showed a stable supporting structure, inhibiting exogenous cell invasion during the regeneration process, higher regenerated axons at the mid-conduit, and distal nerve site of implanted grafts compared to the silicone and non-asymmetric groups at 4 and 6 weeks. The asymmetric structure in the conduit wall enhanced the removal of the blockage of the waste drain from the inner inflamed wound in the early stage.
Vleggeert-Lankamp et al., 2006 [50]	In vivo: sciatic nerve of female Wistar rat (n = 38).	Poly(ε-caprolactone)	NaCl used as a porosifying agent in the preparation of porous structures	Autografted; grafted nonporous; grafted with pores: outer layer: macroporous (10–230 μm) and inner layer microporous (1–10 μm), macroporous (10–230 μm) or nonporous.	Microporous nerve grafts performed better than nonporous and macroporous grafts. Formation of a tissue bridge with a large diameter, myelinated nerve fibers, more nerve fibers present distal to the graft, the electrophysiological response rate was higher, and the decrease in muscle cross-sectional area was smaller.
Oh et al., 2008 [12]	In vivo: Sciatic nerve of Sprague–Dawley rats (n = 63).	Poly(lactic-co-glycolic acid) (PLGA) and Pluronic F127	Modified immersion precipitation method	Porosity: inner surface of the tube with nano-size pores (~50 nm); outer surface with micro-size pores (~50 μm) Nonporous: silicon tubes	PLGA/Pluronic F127 NGC (inner surface pore: ~50 nm) prevented the infiltration of fibrous tissue, retained neurotrophic factors, and provided optimal nutrient infiltration. NGC with the outer surface with micro-sized pores (~50 μm) allowed vascular growth for effective delivery of nutrients and oxygen, allowing rapid and continuous axonal growth from the proximal to the distal direction in ~4 weeks.
Oh et al., 2012 [51]	In vivo: Sciatic nerve of rats (n = 48).	Poly(caprolactone) (PCL)/Pluronic F127	Immersion precipitation method	Membrane with nano-size pores (~100 nm) and opposite surface (mold contact side) with micro-size pores (~200 μm)	Nerve fibers regenerated along the longitudinal direction through the NGC with a nano-porous inner surface, while they were grown toward the porous wall of the NGC with a micro-porous inner surface.
Choi et al., 2014 [52]	In vivo: Recurrent laryngeal nerve of female New Zealand rabbits (n = 28).	Poly(caprolactone) (PCL)/Pluronic F127	Immersion precipitation method	Asymmetrically porous NGC with selective permeability (inner surface, nano-sized pores; outer surface, micro-sized pores) Nonporous silicone tube. Wall thickness ~0.4 mm, inner diameter of ~1.5 mm and a length of ~12 mm.	Significantly better vocal cord paralysis in the asymmetrically porous PCL/F127 NGC than in the silicone tube. Asymmetrically porous PCL/F127 NGC tubes facilitated nerve regeneration compared with nonporous silicone tubes.