• The Influence of Topological, Electrical and Mechanical Characteristics of 3D Bio-printed Scaffold on the Enhancment of Peripheral Nerves Regeneration.
  • ayda ziyaei,1 Mehdi Atari,2,*
    1. Apadana Institute of Higher Education
    2. Apadana Institute of Higher Education


  • Introduction: The incidence of peripheral nerve (PN) injury in traumatized patients is approximately 5% resulting in a marked decline in life quality. A number of factors including: ischemic, mechanical, chemical, and physical ones, can harm the nervous system (NS). Nerve transection, the breakdown of blood-nerve barriers, pain, sensory disruption, and physical and psychological harms can be the result of NS injury. PN injury has been extensively studied to be treated through nerve guide conduits, as an alternative to nerve auto-grafts and allografts. The preferred therapeutic approach for nervous tissue engineering in recent years is using electroactive scaffolds with extremely accurate biomaterial deposition and cells encapsulation using 3D bioprinting technology with conductive hydrogels. Special attention needs to be given to the important role of conductive 3D matrices in neural relay restoration according to the electrophysiological properties of nerve tissues.
  • Methods: Nerve guide conduits have been made using the majority of synthetic and natural polymers from composite materials, metals, polymers, and ceramics. Cells and/or biological materials. The most important attributes are biocompatibility, biodegradability, and the necessary mechanical properties. Few biological materials, including agarose, chitosan, and a biodegradable polyurethane (PU)-modified poly(ε-caprolactone) (PCL) hydrogel, have been used for 3D printing of living tissues. Nerve regenerating cells frequently include stem cells, mature cells, genetically altered cells and stellate cells (SCs). The most recent developments in 3D printing technologies include: inkjet, extension-based, stereolithography, and projection-based printing. Their beneficial option is the flexibility to customize any desired shape and the addition of appropriate active cells to them. Digital light processing (DLP-based) technology allows the continuous fabrication of customized nerve conduits at a high rate of speed and precision.
  • Results: Nerve guide conduits are tubular structures with mechanical and biochemical properties required for nerve regeneration prepared by natural and/or synthetic biopolymers using tissue engineering techniques. This bionic structure, enable the longitudinal arrangement of regenerated axons, mechanical qualities to support nerve structure, enough nutritional permeability, electrical conductivity, flexibility, and suitable biodegradability to permit unrestricted cell elongation, diffusion, and signal transmission.  Nerve guide conduits with semipermeable/asymmetric porous outer walls were deemed to be the best by inhibiting fibroblast infiltration and allowing mass diffusion transfer. The mechano-transduction mismatch between cells and matrix, altering cell phenotype, proliferation, and differentiation, was thought to be the possible mechanism. Fan et al. created three hydrogels with different stiffness levels and showed iNSCs embedded in hydrogels with low modulus could differentiate and survive effectively. Using freeze-drying technology, Bozkurt et al. created highly oriented 3D collagen scaffolds with the ability to direct axon regeneration in vitro. Mei et al. created a range of pliable and supple three-dimensional hydrogels and discovered that axon orientation is parallel to the direction of mechanical stretching. A suitable level of tube wall permeability should facilitate the flow of blood and nutrients, prevent the infiltration of cells that form scar tissue and aid in the removal of metabolic waste. According to certain researches, the ideal ratio for peripheral nerve repair is between 10–40 μm in micropore size and 80% porosity. Moreover, carbon-based materials, such as graphene, have high electrical conductivity, making them useful to stimulate neighboring nerve cells' glial and neuronal cells. After PN engineering, polydopamine and RGD modified 3D conductive scaffolds can greatly enhance neural expression both in vivo and in vitro and encourage axon regeneration and re-myelination.
  • Conclusion: In contrast to conventional manufacturing techniques, 3D printed nerve conduits are inexpensive, highly effective, and simple to prepare. The "ideal" nerve guide conduits should be biocompatible, degradable, and conductive at all stages of nerve regeneration and provide nutritional support. Currently, the FDA has approved several collagen-based synthetic scaffolds, such as NeuroGen®, NeuroMatrix®, NeuroTube® and SaluChannel® which are used limitedly to nerve deficits less than 3 cm. Additionally, functional inks and 3D printing techniques have opened up new possibilities for customized bioelectronics and devices, and future treatment paradigms are anticipated to be brought about by clever integrated computational processing. The creation of novel additive materials and the manufacturing of nerve guide conduits with nano-precision, growth factors, or growth factors gradients will be the focus of future effort.
  • Keywords: 3d bioprinting nerve tissue engineering biocompatibility electrocondutive 3d scaffold