Development of BDNF/NGF/IKVAV Peptide Modified and Gold Nanoparticle Conductive PCL/PLGA Nerve Guidance Conduit for Regeneration of the Rat Spinal Cord Injury.

Spinal cord injuries are very common worldwide, leading to permanent nerve function loss with devastating effects in the affected patients. The challenges and inadequate results in the current clinical treatments are leading scientists to innovative neural regenerative research. Advances in nanoscience and neural tissue engineering have opened new avenues for spinal cord injury (SCI) treatment. In order for designed nerve guidance conduit (NGC) to be functionally useful, it must have ideal scaffold properties and topographic features that promote the linear orientation of damaged axons. In this study, it is aimed to develop channeled polycaprolactone (PCL)/Poly-D,L-lactic-co-glycolic acid (PLGA) hybrid film scaffolds, modify their surfaces by IKVAV pentapeptide/gold nanoparticles (AuNPs) or polypyrrole (PPy) and investigate the behavior of motor neurons on the designed scaffold surfaces in vitro under static/bioreactor conditions. Their potential to promote neural regeneration after implantation into the rat SCI by shaping the film scaffolds modified with neural factors into a tubular form is also examined. It is shown that channeled groups decorated with AuNPs highly promote neurite orientation under bioreactor conditions and also the developed optimal NGC (PCL/PLGA G1-IKVAV/BDNF/NGF-AuNP50) highly regenerates SCI. The results indicate that the designed scaffold can be an ideal candidate for spinal cord regeneration.

Design of IKVAV peptide/gold nanoparticle decorated, micro/nano-channeled PCL/PLGA film scaffolds for neuronal differentiation and neurite outgrowth.

In the field of neural tissue engineering, intensive efforts are being made to develop tissue scaffolds that can support an effective functional recovery and neural development by guiding damaged axons and neurites. Micro/nano-channeled conductive biomaterials are considered a promising approach for repairing the injured neural tissues. Many studies have demonstrated that the micro/nano-channels and aligned nanofibers could guide the neurites to extend along the direction of alignment. However, an ideal biocompatible scaffold containing conductive arrays that could promote effective neural stem cell differentiation and development, and also stimulate high neurite guidance has not been fully developed. In the current study, we aimed to fabricate micro/nano-channeled polycaprolactone (PCL)/Poly-d,l-lactic-co-glycolic acid (PLGA) hybrid film scaffolds, decorate their surfaces with IKVAV pentapeptide/gold nanoparticles (AuNPs), and investigate the behavior of PC12 cells and neural stem cells (NSCs) on the developed biomaterial under static/bioreactor conditions. Here we show that channeled groups decorated with AuNPs highly promote neurite outgrowth and neuronal differentiation along linear lines in the presence of electrical stimulation, compared with the polypyrrole (PPy) coating, which has been used traditionally for many years. Hopefully, this newly developed channeled scaffold structure (PCL/PLGA-AuNPs-IKVAV) could help to support long-distance axonal regeneration and neuronal development after different neural damages.

The effects of surface functionality and size of gold nanoparticles on neuronal toxicity, apoptosis, ROS production and cellular/suborgan biodistribution.

Gold nanoparticles are emerging as promising nanomaterials to create nanoscale therapeutic delivery systems. The aim of the study was to synthesis of highly monodisperse and stable gold nanoparticles functionalized with polyethyleneimine (PEI) and polyethylene glycol (PEG), multiparametric investigation of their neuronal toxicological effects and evaluation of the cellular/suborgan biodistribution. Gold nanoparticles (AuNP20 and AuNP50) were synthesized and their surfaces were electrostatically modified by PEI and PEG. Dorsal root ganglion (DRG) sensory neurones were isolated from BALB/c mice. Cell viability, apoptosis and ROS production were evaluated in vitro. Cellular and suborgan biodisribution of the AuNPs were investigated using inductively coupled plasma mass spectrometry (ICP-MS) technique. PEI and PEG surface coating increased both biocompatibility and biodistribution of the AuNPs. ICP-MS measurements showed the presence of gold in liver, spleen, kidney, heart, blood and brain within a 30 days period. The size and surface chemistry of the AuNPs are important parameters for potential nanoteranostic applications in the future studies.

Functionalized gold nanoparticles manifested as potent carriers for nucleolar targeting.

It is generally known that gold nanoparticles are localised in the cytoplasm and, if synthesised in small sizes or functionalized with specific proteins, they enter the cell nucleus. However, there is no report emphasising the importance of surface functionalization in their accumulation in the nucleolus. Here, for the first time in the literature, it is proposed that functionalization of gold nanoparticles with a thin layer of polyethyleneimine (PEI) spearheads them to the nucleolus of hard-to-transfect post-mitotic dorsal root ganglion neurones in a size-independent manner. As a potential for theranostic applications, it was found that functionalization with a thin layer of PEI affected the emission signal intensity of gold nanoparticles so that the cellular biodistribution of nanoparticles was visualised clearly under both confocal and two-photon microscopes.