Peripheral nerve scaffold assembly

To mimick peripheral nerve, a nanofibrous assembly consisting of a nanofibrous tube and nanofibrous yarn in the lumen of the tube was constructed by Koh et al (2010). The tubular scaffold was fabricated by depositing nanofibers on a rotating rod followed by the removal of the tube from the rod. Nanofibrous yarn was constructed using a liquid flow method although other methods that can produced aligned fibers yarn can be used. A bundle of yarns were gathered and thread through the lumen of the tube and this can be done using a metal hook.

Clements et al (2009) used the contact guidance ability of nanofibers to construct a hybrid setup comprising of aligned nanofiber membrane and commercially available nerve tube [Clements et al 2009]. The tube was first cut into segments to allow placement of the membrane inside before gluing back together. The membrane with nanofibers aligned in the longitudinal axis of the tube was glued into the tube. Two different configurations were constructed as shown in the diagrams below.

Construction of nerve tube with guidance channel. A single membrane consisting of longitudinally aligned nanofibers were glued to lumen of the tube [click image to enlarge].

Nerve tube with three layers of nanofibrous membrane inserted into the lumen

A simple way of introducing luminal structure is to roll a relatively stiff membrane into a conduit with a spiral cross section. Zennifer et al (2025) used a combination of 3D-printed thermoplastic polyurethane (TPU) fiber lattice and electrospun poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) (PHBV) fibers to first form a flat sheet. The sheet is subsequently rolled tightly using a steel rod and heat sealed to form a conduit. An advantage of using 3D printing is that the infill density of the grid structure can be controlled. The electrospun fibers were deposited directly on the 3D printed grid. Aligned fibers were obtained by electrospinning on the printed grid mounted on a rotating drum. To enhance contact guidance of the peripheral nerve, the electrospun aligned fibers were oriented along the length of the conduit. In vivo tests using 10 mm sciatic nerve defect in Wistar rats treated with the conduit showed muscle innervation and axon healing comparable to autografts over 4 months.

The spiral micro-nano structured NGC morphology demonstrates fabrication feasibility for both larger (human) and smaller (rat) sizes. (a & b) Optical and SEM images present examples of aligned PHBV nanofibers on the TPU microfiber lattice. (c) A 2 mm × 10 mm spiral NGC example was produced by rolling and heat sealing the edges. (d) Larger NGC examples, applicable to human nerves, are shown. The green arrow indicates TPU microfibers, and the yellow arrow points to PHBV nanofibers in the spiral NGC. (e) Water contact angle measurements indicate improved hydrophilicity for rPHBV/aPHBV compared to TPU. (f) Micro-CT images of smaller NGCs used for rat sciatic nerve reconstruction are presented [Zennifer et al 2025].

For the nerve guidance conduit described by Koh et al 2010, it is also possible to use the nanofibrous yarn with commercially available tube since both components (yarn and tube) are manufactured separately before combining. As seen in the picture below, a simple hook design can be used to push the bundle of yarns into a tube. The density of the yarn can be varied to achieve a balance between contact guidance and obstruction of nerve axon.

A common drawback of guidance channel or film is that the materials used for guiding are themselves a barrier to axon growth or neurite. In a scaffold developed by Brown (2012) to be used for spinal cord treatment, its architecture introduces guidance function while minimizes neurite obstruction. Instead of fibrous yarn or film which creates a large signature, longitudinally aligned electrospun monofilaments were assembled in the lumen and encapsulated with an outer nanofibrous covering. A clear advantage of monofilaments is that the individual cross sectional diameter is so small that neurite may easily get pass it. The challenge is to create spacings between the filaments that is sufficiently large for the neurite to get through. The study has already demonstrated alignment of endothelial cells at its core and it is likely that neurite will be guided through as well.

Construction of this scaffold is based on two electrospinning setup concepts. To form the longitudinally aligned monofilament core, a parallel electrodes setup was used. The electrodes may be made out of small diameter rods with their ends facing one another. This way, fibers will bridge across the gap while charges on each fiber will cause them to repel one another, thereby creating the space for neurite growth. Next, without removing the fibers from the rods, the fibers (while still attached to the rod) are placed against a flat plate. A schematic of the process is shown in the figure below. Electrospinning is then carried out to depost more fibers over the longitudinally aligned fibers. Due to the presence of the repulsive longitudinally aligned fibers, the subsequent electrospinning jet tends to deposit the fibers across the longitudinally aligned fibers. The deposited fibers are used to wrap the longitudinally aligned fibers.

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