Natural Biomaterials as Instructive Engineered Microenvironments That Direct Cellular Function in Peripheral Nerve Tissue Engineering

Nerve tissue function and regeneration depend on precise and well-synchronised spatial and temporal control of biological, physical, and chemotactic cues, which are provided by cellular components and the surrounding extracellular matrix. Therefore, natural biomaterials currently used in peripheral nerve tissue engineering are selected on the basis that they can act as instructive extracellular microenvironments. Despite emerging knowledge regarding cell-matrix interactions, the exact mechanisms through which these biomaterials alter the behaviour of the host and implanted cells, including neurons, Schwann cells and immune cells, remain largely unclear. Here, we review some of the physical processes by which natural biomaterials mimic the function of the extracellular matrix and regulate cellular behaviour. We also highlight some representative cases of controllable cell microenvironments developed by combining cell biology and tissue engineering principles.

Fabrication and evaluation of porous and conductive nanofibrous scaffolds for nerve tissue engineering

Peripheral nerve repair is still one of the major clinical challenges which has received a great deal of attention. Nerve tissue engineering is a novel treatment approach that provides a permissive environment for neural cells to overcome the constraints of repair. Conductivity and interconnected porosity are two required characteristics for a scaffold to be effective in nerve regeneration. In this study, we aimed to fabricate a conductive scaffold with controlled porosity using polycaprolactone (PCL) and chitosan (Chit), FDA approved materials for the use in implantable medical devices. A novel method of using tetrakis (hydroxymethyl) phosphonium chloride (THPC) and formaldehyde was applied for in situ synthesis of gold nanoparticles (AuNPs) on the scaffolds. In order to achieve desirable porosity, different percentage of polyethylene oxide (PEO) was used as sacrificial fiber. Fourier transform infrared spectroscopy (FTIR) and field emission scanning electron microscopy (FE-SEM) results demonstrated the complete removing of PEO from the scaffolds after washing and construction of interconnected porosities, respectively. Elemental and electrical analysis revealed the successful synthesis of AuNPs with uniform distribution and small average diameter on the PCL/Chit scaffold. Contact angle measurements showed the effect of porosity on hydrophilic properties of the scaffolds, where the porosity of 75–80% remarkably improved surface hydrophilicity. Finally, the effect of conductive nanofibrous scaffold on Schwann cells morphology and vaibility was investigated using FE-SEM and MTT assay, respectively. The results showed that these conductive scaffolds had no cytotoxic effect and support the spindle-shaped morphology of cells with elongated process which are typical of Schwann cell cultures.