Fabrication and characterization of bioresorbable, electroactive and highly regular nanomodulated cell interfaces.

Biomaterial-based implantable scaffolds capable of promoting physical and functional reconnection of injured spinal cord and nerves represent the latest frontier in neural tissue engineering. Here, we report the fabrication and characterization of self-standing, biocompatible and bioresorbable substrates endowed with both controlled nanotopography and electroactivity, intended for the design of transient implantable scaffolds for neural tissue engineering. In particular, we obtain conductive and nano-modulated poly(D,L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) free-standing films by simply iterating a replica moulding process and coating the polymer with a thin layer of poly(3,4-ethylendioxythiophene) polystyrene sulfonate (PEDOT:PSS). The capability of the substrates to retain both surface patterning and electrical properties when exposed to a liquid environment has been evaluated by atomic force microscopy, electrochemical impedance spectroscopy and thermal characterizations. In particular, we show that PLA-based films maintain their surface nano-modulation for up to three weeks of exposure to a liquid environment, a time sufficient for promoting axonal anisotropic sprouting and growth during neuronal cell differentiation. In conclusion, the developed substrates represent a novel and easily-tunable platform to design bioresorbable implantable devices featuring both topographic and electrical cues. .

The limelight of adipose-derived stem cells in the landscape of neural tissue engineering for peripheral nerve injury.

BACKGROUND AND AIMS: Challenges in treating peripheral nerve injury include prolonged repair time and insufficient functional recovery. Stem cell therapy coupled with neural tissue engineering has been shown to induce nerve regeneration following peripheral nerve injury. Among these stem cells, adipose-derived stem cells (ADSCs) are preferred due to their accessibility, expansion, multidirectional differentiation, and production of essential nutrient factors for nerve growth. In recent years, ADSC-laden nerve guide conduit has been utilized to enhance the therapeutic effects of tissue-engineered nerve grafts. This review explores existing research that recognizes the roles played by ADSCs in inducing peripheral nerve regeneration following injury and summarizes the different methods of application of ADSC-laden nerve conduit in neural tissue engineering.

Innovative 3D bioprinting approaches for advancing brain science and medicine: a literature review.

The rapid advancements in 3D printing technology have revolutionized the field of tissue engineering, particularly in the development of neural tissues for the treatment of nervous system diseases. Brain neural tissue, composed of neurons and glial cells, plays a crucial role in the functioning of the brain, spinal cord, and peripheral nervous system by transmitting nerve impulses and processing information. By leveraging 3D bioprinting and bioinks, researchers can create intricate neural scaffolds that facilitate the proliferation and differentiation of nerve cells, thereby promoting the repair and regeneration of damaged neural tissues. This technology allows for the precise spatial arrangement of various cell types and scaffold materials, enabling the construction of complex neural tissue models that closely mimic the natural architecture of the brain. Human-induced pluripotent stem cells (hiPSCs) have emerged as a groundbreaking tool in neuroscience research and the potential treatment of neurological diseases. These cells can differentiate into diverse cell types within the nervous system, including neurons, astrocytes, microglia, oligodendrocytes, and Schwann cells, providing a versatile platform for studying neural networks, neurodevelopment, and neurodegenerative disorders. The use of hiPSCs also opens new avenues for personalized medicine, allowing researchers to model diseases and develop targeted therapies based on individual patient profiles. Despite the promise of direct hiPSC injections for therapeutic purposes, challenges such as poor localization and limited integration have led to the exploration of biomaterial scaffolds as supportive platforms for cell delivery and tissue regeneration. This paper reviews the integration of 3D bioprinting technologies and bioink materials in neuroscience applications, offering a unique platform to create complex brain and tissue architectures that mimic the mechanical, architectural, and biochemical properties of native tissues. These advancements provide robust tools for modelling, repair, and drug screening applications. The review highlights current research, identifies research gaps, and offers recommendations for future studies on 3D bioprinting in neuroscience. The investigation demonstrates the significant potential of 3D bioprinting to fabricate brain-like tissue constructs, which holds great promise for regenerative medicine and drug testing models. This approach offers new avenues for studying brain diseases and potential treatments.

Incorporation of montmorillonite into microfluidics-generated chitosan microfibers enhances neuron-like PC12 cells for application in neural tissue engineering.

The complexity in structure and function of the nervous system, as well as its slow rate of regeneration, makes it more difficult to treat it compared to other tissues. Neural tissue engineering aims to create an appropriate environment for nerve cell proliferation and differentiation. Fibrous scaffolds with suitable morphology and topography and better mimicry of the extracellular matrix have been promising for the alignment and migration of neural cells. On this premise, to improve the properties of the scaffold, we combined montmorillonite (MMT) with chitosan (CS) polymer and created microfibers with variable diameters and varied concentrations of MMT using microfluidic technology and tested its suitability for the rat pheochromocytoma cell line (PC12). According to the findings, CS/MMT 0.1 % compared to CS/MMT 0 % microfibers showed a 201 MPa increase in Young's modulus, a 68 mS/m increase in conductivity, and a 1.4-fold increase in output voltage. Analysis of cell mitochondrial activity verified the non-toxicity, resulting in good cell morphology with orientation along the microfiber. Overall, the results of this project showed that with a low concentration of MMT, the properties of microfibers can be significantly improved and a suitable scaffold can be designed for neural tissue engineering.

Recent Advances in the Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) is a complex, multifaceted, progressive, and yet incurable complication that can cause irreversible damage to the individual, family, and society. In recent years strategies for the management and rehabilitation of SCI besides axonal regeneration, remyelination, and neuronal plasticity of the injured spinal cord have significantly improved. Although most of the current research and therapeutic advances have been made in animal models, so far, no specific and complete treatment has been reported for SCI in humans. The failure to treat this complication has been due to the inherent neurological complexity and the structural, cellular, molecular, and biochemical characteristics of spinal cord injury. In this review, in addition to elucidating the causes of spinal cord injury from a molecular and pathophysiological perspective, the complexity and drawbacks of neural regeneration that lead to the failure in SCI treatment are described. Also, recent advances and cutting-edge strategies in most areas of SCI treatment are presented.

Comparison of Printable Biomaterials for Use in Neural Tissue Engineering: An In Vitro Characterization and In Vivo Biocompatibility Assessment.

Nervous system traumatic injuries are prevalent in our society, with a significant socioeconomic impact. Due to the highly complex structure of the neural tissue, the treatment of these injuries is still a challenge. Recently, 3D printing has emerged as a promising alternative for producing biomimetic scaffolds, which can lead to the restoration of neural tissue function. The objective of this work was to compare different biomaterials for generating 3D-printed scaffolds for use in neural tissue engineering. For this purpose, four thermoplastic biomaterials, ((polylactic acid) (PLA), polycaprolactone (PCL), Filaflex (FF) (assessed here for the first time for biomedical purposes), and Flexdym (FD)) and gelatin methacrylate (GelMA) hydrogel were subjected to printability and mechanical tests, in vitro cell-biomaterial interaction analyses, and in vivo biocompatibility assessment. The thermoplastics showed superior printing results in terms of resolution and shape fidelity, whereas FD and GelMA revealed great viscoelastic properties. GelMA demonstrated a greater cell viability index after 7 days of in vitro cell culture. Moreover, all groups displayed connective tissue encapsulation, with some inflammatory cells around the scaffolds after 10 days of in vivo implantation. Future studies will determine the usefulness and in vivo therapeutic efficacy of novel neural substitutes based on the use of these 3D-printed scaffolds.

Peripheral nerve injury repair by electrical stimulation combined with graphene-based scaffolds.

Peripheral nerve injury (PNI) is a common clinical problem, which due to poor recovery often leads to limb dysfunction and sensory abnormalities in patients. Tissue-engineered nerve guidance conduits (NGCs) that are designed and fabricated from different materials are the potential alternative to nerve autografts. However, translation of these NGCs from lab to commercial scale has not been well achieved. Complete functional recovery with the aid of NGCs in PNI becomes a topic of general interest in tissue engineering and regeneration medicine. Electrical stimulation (ES) has been widely used for many years as an effective physical method to promote nerve repair in both pre-clinical and clinical settings. Similarly, ES of conductive and electroactive materials with a broad range of electrical properties has been shown to facilitate the guidance of axons and enhance the regeneration. Graphene and its derivatives possess unique physicochemical and biological properties, which make them a promising outlook for the development of synthetic scaffolds or NGCs for PNI repair, especially in combination with ES. Considering the discussion regarding ES for the treatment of PNI must continue into further detail, herein, we focus on the role of ES in PNI repair and the molecular mechanism behind the ES therapy for PNI, providing a summary of recent advances in context of graphene-based scaffolds (GBSs) in combination with ES. Future perspectives and some challenges faced in developing GBSs are also highlighted with the aim of promoting their clinical applications.

Recent progresses in neural tissue engineering using topographic scaffolds.

Neural tissue engineering as alternatives to recover damaged tissues and organs is getting more and more attention due to the lack of regeneration ability of natural tissue nervous system after injury. Particularly, topographic scaffolds are one of the critical elements to guide nerve orientation and reconnection with characteristics of mimic the natural extracellular matrix. This review focuses on scaffolds preparation technologies, topographical features, scaffolds-based encapsulations delivery strategies for neural tissue regeneration, biological functions on nerve cell guidance and regeneration, and applications of topographic scaffolds in vivo and in vitro. Here, the recent developments in topographic scaffolds for neural tissue engineering by simulating neural cell topographic orientation and differentiation are presented. We also explore the challenges and future perspectives of topographical scaffolds in clinical trials and practical applications.

Human induced pluripotent stem cell-derived planar neural organoids assembled on synthetic hydrogels.

The tailorable properties of synthetic polyethylene glycol (PEG) hydrogels make them an attractive substrate for human organoid assembly. Here, we formed human neural organoids from iPSC-derived progenitor cells in two distinct formats: (i) cells seeded on a Matrigel surface; and (ii) cells seeded on a synthetic PEG hydrogel surface. Tissue assembly on synthetic PEG hydrogels resulted in three dimensional (3D) planar neural organoids with greater neuronal diversity, greater expression of neurovascular and neuroinflammatory genes, and reduced variability when compared with tissues assembled upon Matrigel. Further, our 3D human tissue assembly approach occurred in an open cell culture format and created a tissue that was sufficiently translucent to allow for continuous imaging. Planar neural organoids formed on PEG hydrogels also showed higher expression of neural, vascular, and neuroinflammatory genes when compared to traditional brain organoids grown in Matrigel suspensions. Further, planar neural organoids contained functional microglia that responded to pro-inflammatory stimuli, and were responsive to anti-inflammatory drugs. These results demonstrate that the PEG hydrogel neural organoids can be used as a physiologically relevant in vitro model of neuro-inflammation.

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.

Hydrodynamic Assembly of Astrocyte Cells in Conductive Hollow Microfibers.

The manufacturing of 3D cell scaffoldings provides advantages for modeling diseases and injuries as it enables the creation of physiologically relevant platforms. A triple-flow microfluidic device is developed to rapidly fabricate alginate/graphene hollow microfibers based on the gelation of alginate induced with CaCl2 . This five-channel microdevice actualizes continuous mild fabrication of hollow fibers under an optimized flow rate ratio of 300:200:100 µL min-1 . The polymer solution is 2.5% alginate in 0.1% graphene and a 30% polyethylene glycol solution is used as the sheath and core solutions. The biocompatibility of these conductive microfibers by encapsulating mouse astrocyte cells (C8D1A) within the scaffolds is investigated. The cells can successfully survive both the manufacturing process and prolonged encapsulation for up to 8 days, where there is between 18-53% of live cells on both the alginate microfibers and alginate/graphene microfibers. These unique 3D hollow scaffolds can significantly enhance the available surface area for nutrient transport to the cells. In addition, these conductive hollow scaffolds illustrate unique advantages such as 0.728 cm3  gr-1 porosity and two times more electrical conductivity in comparison to alginate scaffolds. The results confirm the potential of these scaffolds as a microenvironment that supports cell growth.

Hesperidin guided injured spinal cord neural regeneration with a combination of MWCNT-collagen-hyaluronic acid composite: In-vitro analysis.

Restoring the lost bioelectrical signal transmission along with the appropriate microenvironment is one of the major clinical challenges in spinal cord regeneration. In the current research, we developed a polysaccharide-based protein composite Multiwalled Carbon Nanotubes (MWCNTs)/ Collagen (Col)/ Hyaluronic acid (HA) composite with Hesperidin (Hes) natural compound to investigate its combined therapeutic effect along with biocompatibility, antioxidant activity, and electrical conductivity. The multifunctional composites were characterized via FT-IR, XRD, SEM, HR-TEM, BET, C.V, and EIS techniques. The electrical conductivity and modulus of the MWCNT-Col-HA-Hes were 0.06 S/cm and 12.3 kPa, similar to the native spinal cord. The in-vitro Cytotoxicity, cell viability, antioxidant property, and cell migration ability of the prepared composites were investigated with a PC-12 cell line. In-vitro studies revealed that the multifunctional composites show higher cell viability, antioxidant, and cell migration properties than the control cells. Reduction of ROS level indicates that the Hes presence in the composite could reduce the cell stress by protecting it from oxidative damage and promoting cell migration towards the lesion site. The developed multifunctional composite can provide the antioxidant microenvironment with compatibility and mimic the native spinal cord by providing appropriate conductivity and mechanical strength for spinal cord tissue regeneration.

In vitro model of neurotrauma using the chick embryo to test regenerative bioimplantation.

Effective repair of spinal cord injury sites remains a major clinical challenge. One promising strategy is the implantation of multifunctional bioscaffolds to enhance nerve fibre growth, guide regenerating tissue and modulate scarring/inflammation processes. Given their multifunctional nature, such implants require testing in models which replicate the complex neuropathological responses of spinal injury sites. This is often achieved using live, adult animal models of spinal injury. However, these have substantial drawbacks for developmental testing, including the requirement for large numbers of animals, costly infrastructure, high levels of expertise and complex ethical processes. As an alternative, we show that organotypic spinal cord slices can be derived from the E14 chick embryo and cultured with high viability for at least 24 days, with major neural cell types detected. A transecting injury could be reproducibly introduced into the slices and characteristic neuropathological responses similar to those in adult spinal cord injury observed at the lesion margin. This included aligned astrocyte morphologies and upregulation of glial fibrillary acidic protein in astrocytes, microglial infiltration into the injury cavity and limited nerve fibre outgrowth. Bioimplantation of a clinical grade scaffold biomaterial was able to modulate these responses, disrupting the astrocyte barrier, enhancing nerve fibre growth and supporting immune cell invasion. Chick embryos are inexpensive and simple, requiring facile methods to generate the neurotrauma model. Our data show the chick embryo spinal cord slice system could be a replacement spinal injury model for laboratories developing new tissue engineering solutions.

Advances in Conductive Hydrogel for Spinal Cord Injury Repair and Regeneration.

Spinal cord injury (SCI) treatment represents a major challenge in clinical practice. In recent years, the rapid development of neural tissue engineering technology has provided a new therapeutic approach for spinal cord injury repair. Implanting functionalized electroconductive hydrogels (ECH) in the injury area has been shown to promote axonal regeneration and facilitate the generation of neuronal circuits by reshaping the microenvironment of SCI. ECH not only facilitate intercellular electrical signaling but, when combined with electrical stimulation, enable the transmission of electrical signals to electroactive tissue and activate bioelectric signaling pathways, thereby promoting neural tissue repair. Therefore, the implantation of ECH into damaged tissues can effectively restore physiological functions related to electrical conduction. This article focuses on the dynamic pathophysiological changes in the SCI microenvironment and discusses the mechanisms of electrical stimulation/signal in the process of SCI repair. By examining electrical activity during nerve repair, we provide insights into the mechanisms behind electrical stimulation and signaling during SCI repair. We classify conductive biomaterials, and offer an overview of the current applications and research progress of conductive hydrogels in spinal cord repair and regeneration, aiming to provide a reference for future explorations and developments in spinal cord regeneration strategies.

Electroconductive Nanofibrous Scaffolds Enable Neuronal Differentiation in Response to Electrical Stimulation without Exogenous Inducing Factors.

Among the various biochemical and biophysical inducers for neural regeneration, electrical stimulation (ES) has recently attracted considerable attention as an efficient means to induce neuronal differentiation in tissue engineering approaches. The aim of this in vitro study was to develop a nanofibrous scaffold that enables ES-mediated neuronal differentiation in the absence of exogenous soluble inducers. A nanofibrous scaffold composed of polycaprolactone (PCL), poly-L-lactic acid (PLLA), and single-walled nanotubes (SWNTs) was fabricated via electrospinning and its physicochemical properties were investigated. The cytocompatibility of the electrospun composite with the PC12 cell line and bone marrow-derived mesenchymal stem cells (BMSCs) was investigated. The results showed that the PCL/PLLA/SWNT nanofibrous scaffold did not exhibit cytotoxicity and supported cell attachment, spreading, and proliferation. ES was applied to cells cultured on the nanofibrous scaffolds at different intensities and the expression of the three neural markers (Nestin, Microtubule-associated protein 2, and ß tubulin-3) was evaluated using RT-qPCR analysis. The results showed that the highest expression of neural markers could be achieved at an electric field intensity of 200 mV/cm, suggesting that the scaffold in combination with ES can be an efficient tool to accelerate neural differentiation in the absence of exogenous soluble inducers. This has important implications for the regeneration of nerve injuries and may provide insights for further investigations of the mechanisms underlying ES-mediated neuronal commitment.

Encapsulation of Human Spinal Cord Progenitor Cells in Hyaluronan-Gelatin Hydrogel for Spinal Cord Injury Treatment.

Transplanting human induced pluripotent stem cells (iPSCs)-derived spinal cord progenitor cells (SCPCs) is a promising approach to treat spinal cord injuries. However, stem cell therapies face challenges in cell survival, cell localization to the targeted site, and the control of cell differentiation. Here, we encapsulated SCPCs in thiol-modified hyaluronan-gelatin hydrogels and optimized scaffold mechanical properties and cell encapsulation density to promote cell viability and neuronal differentiation in vitro and in vivo. Different compositions of hyaluronan-gelatin hydrogels formulated by varying concentrations of poly(ethylene glycol) diacrylate were mechanically characterized by using atomic force microscopy. In vitro SCPC encapsulation study showed higher cell viability and proliferation with lower substrate Young's modulus (200 Pa vs 580 Pa) and cell density. Moreover, the soft hydrogels facilitated a higher degree of neuronal differentiation with extended filament structures in contrast to clumped cellular morphologies obtained in stiff hydrogels (p < 0.01). When transplanted in vivo, the optimized SCPC-encapsulated hydrogels resulted in higher cell survival and localization at the transplanted region as compared to cell delivery without hydrogel encapsulation at 2 weeks postimplantation within the rat spinal cord (p < 0.01). Notably, immunostaining demonstrated that the hydrogel-encapsulated SCPCs differentiated along the neuronal and oligodendroglial lineages in vivo. The lack of pluripotency and proliferation also supported the safety of the SCPC transplantation approach. Overall, the injectable hyaluronan-gelatin hydrogel shows promise in supporting the survival and neural differentiation of human SCPCs after transplantation into the spinal cord.

Three-dimensional nanofibrous sponges with aligned architecture and controlled hierarchy regulate neural stem cell fate for spinal cord regeneration.

Background: Spinal cord injury (SCI) induces neuronal death and disrupts the nerve fiber bundles, which leads to severe neurological dysfunction and even permanent paralysis. A strategy combining biomimetic nanomaterial scaffolds with neural stem cell (NSC) transplantation holds promise for SCI treatment. Methods: Innovative three-dimensional (3D) nanofibrous sponges (NSs) were designed and developed by a combination of directional electrospinning and subsequent gas-foaming treatment. Immunofluorescence, mRNA sequencing, magnetic resonance imaging, electrophysiological analysis, and behavioral tests were used to investigate the in vitro and in vivo regenerative effects of the 3D NSs. Results: The generated 3D NSs exhibited uniaxially aligned nano-architecture and highly controllable hierarchical structure with super-high porosity (99%), outstanding hydrophilicity, and reasonable mechanical performance. They facilitated cell infiltration, induced cell alignment, promoted neuronal differentiation of NSCs, and enhanced their maturation mediated through cellular adhesion molecule pathways. In vivo, the NSC-seeded 3D NSs efficiently promoted axon reinnervation and remyelination in a rat SCI model, with new "neural relays" developing across the lesion gap. These histological changes were associated with regain of function, including increasing the neurological motor scores of SCI rats, from approximately 2 to 16 (out of 21), and decreasing the sensing time in the tape test from 140 s to 36 s. Additionally, the scaffolds led to restoration of ascending and descending electrophysiological signalling. Conclusion: The as-fabricated 3D NSs effectively regulate NSC fates, and an advanced combination of 3D NS design and transplanted NSCs enables their use as an ideal tissue-engineered scaffold for SCI repair.

Potential Application of Orofacial MSCs in Tissue Engineering Nerve Guidance for Peripheral Nerve Injury Repair.

Injury to the peripheral nerve causes potential loss of sensory and motor functions, and peripheral nerve repair (PNR) remains a challenging endeavor. The current clinical methods of nerve repair, such as direct suture, autografts, and acellular nerve grafts (ANGs), exhibit their respective disadvantages like nerve tension, donor site morbidity, size mismatch, and immunogenicity. Even though commercially available nerve guidance conduits (NGCs) have demonstrated some clinical successes, the overall clinical outcome is still suboptimal, especially for nerve injuries with a large gap (≥ 3 cm) due to the lack of biologics. In the last two decades, the combination of advanced tissue engineering technologies, stem cell biology, and biomaterial science has significantly advanced the generation of a new generation of NGCs incorporated with biological factors or supportive cells, including mesenchymal stem cells (MSCs), which hold great promise to enhance peripheral nerve repair/regeneration (PNR). Orofacial MSCs are emerging as a unique source of MSCs for PNR due to their neural crest-origin and easy accessibility. In this narrative review, we have provided an update on the pathophysiology of peripheral nerve injury and the properties and biological functions of orofacial MSCs. Then we have highlighted the application of orofacial MSCs in tissue engineering nerve guidance for PNR in various preclinical models and the potential challenges and future directions in this field.

Microfluidic Systems for Neural Cell Studies.

Whereas the axons of the peripheral nervous system (PNS) spontaneously regenerate after an injury, the occurring regeneration is rarely successful because axons are usually directed by inappropriate cues. Therefore, finding successful ways to guide neurite outgrowth, in vitro, is essential for neurogenesis. Microfluidic systems reflect more appropriately the in vivo environment of cells in tissues such as the normal fluid flow within the body, consistent nutrient delivery, effective waste removal, and mechanical stimulation due to fluid shear forces. At the same time, it has been well reported that topography affects neuronal outgrowth, orientation, and differentiation. In this review, we demonstrate how topography and microfluidic flow affect neuronal behavior, either separately or in synergy, and highlight the efficacy of microfluidic systems in promoting neuronal outgrowth.

Production of Blended Poly(acrylonitrile): Poly(ethylenedioxythiophene):Poly(styrene sulfonate) Electrospun Fibers for Neural Applications.

This study describes, for the first time, the successful incorporation of poly(ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) in Poly(acrylonitrile) (PAN) fibers. While electroconductive PEDOT:PSS is extremely challenging to electrospun into fibers. Therefore, PAN, a polymer easy to electrospun, was chosen as a carrier due to its biocompatibility and tunable chemical stability when cross-linked, particularly using strong acids. PAN:PEDOT:PSS blends, prepared from PEDOT:PSS Clevios PH1000, were electrospun into fibers (PH1000) with a diameter of 515 ± 120 nm, which after being thermally annealed (PH1000 24H) and treated with heated sulfuric acid (PH1000 H2SO4), resulted in fibers with diameters of 437 ± 109 and 940 ± 210 nm, respectively. The fibers obtained over the stepwise process were characterized through infra-red/Raman spectroscopy and cyclic voltammetry. The final fiber meshes showed enhanced electroconductivity (3.2 × 10-3 S cm-1, four-points-assay). Fiber meshes biocompatibility was evaluated using fibroblasts and neural stem cells (NSCs) following, respectively, the ISO10993 guidelines and standard adhesion/proliferation assay. NSCs cultured on PH1000 H2SO4 fibers presented normal morphology and high proliferation rates (0.37 day-1 vs. 0.16 day-1 for culture plate), indicating high biocompatibility for NSCs. Still, the low initial NSC adhesion of 7% calls for improving seeding methodologies. PAN:PEDOT:PSS fibers, here successful produced for the first time, have potential applications in neural tissue engineering and soft electronics.