Journal articles: 'Neural scaffold'

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Sadeghi, Ali, Fatholah Moztarzadeh, Jamshid Aghazadeh Mohandesi, Claudia Grothe, Kirsten Haastert Talini, Ali Reza Zalli, and Reza Jalili Khoshnoud. "In Vitro Assessment of Synthetic Nano Engineered Graft Designed for Further Clinical Study in Nerve Regeneration." International Clinical Neuroscience Journal 5, no. 3 (September 30, 2018): 86–91. http://dx.doi.org/10.15171/icnj.2018.17.

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Background: Electrospun nanofibrous scaffolds are considered as promising candidates in neural tissue regeneration due to their ability to support neural cell attachment, spreading and proliferation. Methods: In this paper, various type of nanofibers scaffold based on polycaprolactone) (PCL) were fabricated using electrospinning. The main drawback of PCL scaffolds is their low bioactivity of scaffold surface. To overcome this surface and composition modification was used to enhanced hydrophilicity and bioactivity of scaffold. Results: The scanning electron microscopy (SEM) results indicate that fiber diameter entirely depends on the solvent system and added component of gelatin and chitosan which by adding gelatin and chitosan fiber diameter decreased. In vitro studies using PC12 cells revealed that the plasma surface modified and blended scaffold with chitosan and gelatin nanofibrous scaffold supports cell attachment, spreading and indicate a significant increase in proliferation of PC12 in the presence of chitosan. The results demonstrated that gelatin and chitosan caused a significant enhancement in the bioactivity of the scaffold, which confirmed by MTT assay and improved the cell spreading and proliferation of neural cell on the scaffolds. Conclusion: Based on the experimental results, the PCL/chitosan/PPy conductive substrate could be used as a potential scaffold for clinical research in the field of neural regeneration and healing.

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Wang, Yuqing, Haoran Yu, Haifeng Liu, and Yubo Fan. "Double coating of graphene oxide–polypyrrole on silk fibroin scaffolds for neural tissue engineering." Journal of Bioactive and Compatible Polymers 35, no. 3 (May 2020): 216–27. http://dx.doi.org/10.1177/0883911520913905.

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The desired scaffolds for neural tissue engineering need to have electrical conductivity. In this study, we doubly coated graphene oxide and polypyrrole on silk fibroin scaffolds (SF@GO-PPY) by a facile method to improve its electrical conductivity. The graphene oxide–polypyrrole double coating was distributed homogeneously on silk fibroin scaffolds. Compared with silk fibroin scaffolds, the SF@GO-PPY scaffold showed higher electrical conductivity, electrochemical property, mechanical property, and thermal stability. The π–π stacking interaction between polypyrrole and graphene oxide might contribute to the superior conductive and electrochemical property of the SF@GO-PPY scaffold. Moreover, in vitro cell experiment carried out on SH-SY5Y cells showed no cytotoxicity of all the scaffolds. Thus, the results indicated that the SF@GO-PPY scaffold might be a suitable candidate for the application in neural regeneration field.

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Ghorbani, Sadegh, Taki Tiraihi, and Masoud Soleimani. "Differentiation of mesenchymal stem cells into neuron-like cells using composite 3D scaffold combined with valproic acid induction." Journal of Biomaterials Applications 32, no. 6 (November 23, 2017): 702–15. http://dx.doi.org/10.1177/0885328217741903.

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The nervous system has little capacity for self-repair after injury because neurons cannot proliferate owing to lack of suitable microenvironment. Therefore, neural tissue engineering that combines neural stem, scaffolds, and growth factors may improve the chance of restoration of damaged neural tissues. A favorable niche for neural regeneration would be both fibrous and electrically conductive scaffolds. Human Wharton jelly-derived mesenchymal stem cells were seeded on wet-electrospun 3D scaffolds composed of poly lactic acid coated with natural polymers including alginate and gelatin, followed by a multi-wall carbon nanotube coating. The results show that a wet-electrospun poly lactic acid scaffold at a concentration of 15% w/v had higher porosity (above 80%) than other concentrations. Moreover, the coated scaffold supported the growth of human Wharton jelly-derived mesenchymal stem cells in 3D culture, and were incubated for 21 days with 1 mM valproic acid as the inducer resulted in improvement in human Wharton jelly-derived mesenchymal stem cells differentiation into neuron-like cells immunoreactivity to nestin, Map2, and neuron specific enolase (NSE), which were also consistent with reverse transcription polymerase chain reaction (RT-PCR) and quantitive Reverse transcription polymerase chain reaction (qRT-PCR) results. The conclusion is that the 3D composite nanofiber poly lactic acid scaffold improved the transdifferentiation of human Wharton jelly-derived mesenchymal stem cells into neuron-like cells.

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Qiu, Chen, Yuan Sun, Jinying Li, Yuchen Xu, Jiayi Zhou, Cong Qiu, Shaomin Zhang, Yong He, and Luyang Yu. "Therapeutic Effect of Biomimetic Scaffold Loaded with Human Amniotic Epithelial Cell-Derived Neural-like Cells for Spinal Cord Injury." Bioengineering 9, no. 10 (October 9, 2022): 535. http://dx.doi.org/10.3390/bioengineering9100535.

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Spinal cord injury (SCI) results in devastating consequences for the motor and sensory function of patients due to neuronal loss and disrupted neural circuits, confronting poor prognosis and lack of effective therapies. A new therapeutic strategy is urgently required. Here, human amniotic epithelial cells (hAEC), featured with immunocompatibility, non-tumorgenicity and no ethical issues, were induced into neural-like cells by a compound cocktail, as evidenced with morphological change and the expression of neural cell markers. Interestingly, the hAEC-neural-like cells maintain the characteristic of low immunogenicity as hAEC. Aiming at SCI treatment in vivo, we constructed a 3D-printed GelMA hydrogel biomimetic spinal cord scaffold with micro-channels, in which hAEC-neural-like cells were well-induced and grown. In a rat full transection SCI model, hAEC-neural-like cell scaffolds that were implanted in the lesion demonstrated significant therapeutic effects; the neural circuit and hindlimb locomotion were partly recovered compared to little affection in the SCI rats receiving an empty scaffold or a sham implantation operation. Thus, the establishment of hAEC-neural-like cell biomimetic scaffolds may provide a safe and effective treatment strategy for SCI.

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Nune, Manasa, Uma Maheswari Krishnan, and Swaminathan Sethuraman. "Decoration of PLGA electrospun nanofibers with designer self-assembling peptides: a “Nano-on-Nano” concept." RSC Advances 5, no. 108 (2015): 88748–57. http://dx.doi.org/10.1039/c5ra13576a.

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A composite neural scaffold which combines the topographical features of electrospun nanofibrous scaffolds and bioactive as well as nanostructured features of designer self-assembling peptides (“Nano on Nano” approach).

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Zhou, Ling, Jiangyi Tu, Guangbi Fang, Li Deng, Xiaoqing Gao, Kan Guo, Jiming Kong, Jing Lv, Weikang Guan, and Chaoxian Yang. "Combining PLGA Scaffold and MSCs for Brain Tissue Engineering: A Potential Tool for Treatment of Brain Injury." Stem Cells International 2018 (August 5, 2018): 1–8. http://dx.doi.org/10.1155/2018/5024175.

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Nerve tissue engineering is an important strategy for the treatment of brain injuries. Mesenchymal stem cell (MSC) transplantation has been proven to be able to promote repair and functional recovery of brain damage, and poly (lactic-co-glycolic acid) (PLGA) has also been found to have the capability of bearing cells. In the present study, to observe the ability of PLGA scaffold in supporting the adherent growth of MSCs and neurons in vivo and vitro and to assess the effects of PLGA scaffold on proliferation and neural differentiation of MSCs, this study undertakes the following steps. First, MSCs and neurons were cultured and labeled with green fluorescent protein (GFP) or otherwise identified and the PLGA scaffold was synthesized. Next, MSCs and neurons were inoculated on PLGA scaffolds and their adhesion rates were investigated and the proliferation of MSCs was evaluated by using MTT assay. After MSCs were induced by a neural induction medium, the morphological change and neural differentiation of MSCs were detected using scanning electron microscopy (SEM) and immunocytochemistry, respectively. Finally, cell migration and adhesion in the PLGA scaffold in vivo were examined by immunohistochemistry, nuclear staining, and SEM. The experimental results demonstrated that PLGA did not interfere with the proliferation and neural differentiation of MSCs and that MSCs and neuron could grow and migrate in PLGA scaffold. These data suggest that the MSC-PLGA complex may be used as tissue engineering material for brain injuries.

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Rahimi-Sherbaf, Fatemeh, Samad Nadri, Ali Rahmani, and Atousa Dabiri Oskoei. "Placenta mesenchymal stem cells differentiation toward neuronal-like cells on nanofibrous scaffold." BioImpacts 10, no. 2 (March 26, 2020): 117–22. http://dx.doi.org/10.34172/bi.2020.14.

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Introduction: Transplantation of stem cells with a nanofibrous scaffold is a promising approach for spinal cord injury therapy. The aim of this work was to differentiate neural-like cells from placenta-derived mesenchymal stem cells (PDMSCs) using suitable induction reagents in three (3D) and two dimensional (2D) culture systems. Methods: After isolation and characterization of PDMSCs, the cells were cultivated on poly-L-lactide acid (PLLA)/poly caprolactone (PCL) nanofibrous scaffold and treated with a neuronal medium for 7 days. Electron microscopy, qPCR, and immunostaining were used to examine the differentiation of PDMSCs (on scaffold and tissue culture polystyrene [TCPS]) and the expression rate of neuronal markers (beta-tubulin, nestin, GFAP, and MAP-2). Results: qPCR analysis showed that beta-tubulin (1.672 fold; P ≤ 0.0001), nestin (11.145 fold; P ≤ 0.0001), and GFAP (80.171; P ≤ 0.0001) gene expressions were higher on scaffolds compared with TCPS. Immunofluorescence analysis showed that nestin and beta-tubulin proteins were recognized in the PDMSCs differentiated on TCPS and scaffold after 7 days in the neuroinductive differentiation medium. Conclusion: Taken together, these results delegated that PDMSCs differentiated on PLLA/PCL scaffolds are more likely to differentiate towards diversity lineages of neural cells. It proposed that PDMSCs have cell subpopulations that have the capability to be differentiated into neurogenic cells.

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Gelain, Fabrizio, Andrea Lomander, Angelo L. Vescovi, and Shuguang Zhang. "Systematic Studies of a Self-Assembling Peptide Nanofiber Scaffold with Other Scaffolds." Journal of Nanoscience and Nanotechnology 7, no. 2 (February 1, 2007): 424–34. http://dx.doi.org/10.1166/jnn.2007.154.

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A designer self-assembling peptide nanofiber scaffold has been systematically studied with 10 commonly used scaffolds in a several week study using neural stem cells (NSC), a potential therapeutic source for cellular transplantations in nervous system injuries. These cells not only provide a good in vitro model for the development and regeneration of the nervous system, but may also be helpful in testing for cytotoxicity, cellular adhesion, and differentiation properties of biological and synthetic scaffolds used in medical practices. We tested the self-assembling peptide nanofiber scaffold with the most commonly used scaffolds for tissue engineering and regenerative medicine including PLLA, PLGA, PCLA, collagen I, collagen IV, and Matrigel. Additionally, each scaffold was coated with laminin in order to evaluate the utility of this surface treatment. Each scaffold was evaluated by measuring cell viability, differentiation and maturation of the differentiated stem cell progeny (i.e. progenitor cells, astrocytes, oligodendrocytes, and neurons) over 4 weeks. The optimal scaffold should show high numbers of living and differentiated cells. In addition, it was demonstrated that the laminin surface treatment is capable of improving the overall scaffold performance. The designer self-assembling peptide RADA16 nanofiber scaffold represents a new class of biologically inspired material. The well-defined molecular structure with considerable potential for further functionalization and slow drug delivery makes the designer peptide scaffolds a very attractive class of biological material for a number of applications. The peptide nanofiber scaffold is comparable with the clinically approved synthetic scaffolds. The peptide scaffolds are not only pure, but also have the potential to be further designed at the molecular level, thus they promise to be useful for cell adhesion and differentiation studies as well as for future biomedical and clinical studies.

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Liu, Yuan Yuan, Zhen Zhong Han, Shu Hui Fang, Da Li Liu, Ying Liu, and Qing Xi Hu. "Bone Scaffold Forming Filament Width Prediction of LDM Based on the Improved BP Neural Network." Key Engineering Materials 568 (July 2013): 187–92. http://dx.doi.org/10.4028/www.scientific.net/kem.568.187.

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LDM process is used for preparing three-dimensional scaffolds for tissue engineering rapid prototyping technologies. Because of its forming process is complex, which influenced by a variety of factors, so the processing environment is not stable, the forming of scaffold pore size can not be guaranteed, therefore the forming precision is poor. However, the scaffold pore size accuracy is mainly decided by the wire filament width. Neural network theory and development provides a powerful tool for the study of nonlinear systems. This article analyzed the influence factors for forming bone scaffold filament width of LDM process, based on improved BP neural network, using MATLAB software programming, then predicted the filament width. The results show that model prediction error was less than 8%, it has high forecasting precision, and it can be used to guide the LDM process parameter selection and forming precision of prediction.

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Wei, Chih-Chiang. "COLLAPSE WARNING SYSTEM USING LSTM NEURAL NETWORKS FOR CONSTRUCTION DISASTER PREVENTION IN EXTREME WIND WEATHER." JOURNAL OF CIVIL ENGINEERING AND MANAGEMENT 27, no. 4 (April 20, 2021): 230–45. http://dx.doi.org/10.3846/jcem.2021.14649.

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Strong wind during extreme weather conditions (e.g., strong winds during typhoons) is one of the natural factors that cause the collapse of frame-type scaffolds used in façade work. This study developed an alert system for use in determining whether the scaffold structure could withstand the stress of the wind force. Conceptually, the scaffolds collapsed by the warning system developed in the study contains three modules. The first module involves the establishment of wind velocity prediction models. This study employed various deep learning and machine learning techniques, namely deep neural networks, long short-term memory neural networks, support vector regressions, random forest, and k-nearest neighbors. Then, the second module contains the analysis of wind force on the scaffolds. The third module involves the development of the scaffold collapse evaluation approach. The study area was Taichung City, Taiwan. This study collected meteorological data from the ground stations from 2012 to 2019. Results revealed that the system successfully predicted the possible collapse time for scaffolds within 1 to 6 h, and effectively issued a warning time. Overall, the warning system can provide practical warning information related to the destruction of scaffolds to construction teams in need of the information to reduce the damage risk.

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Soleimani, Maryam, Shohreh Mashayekhan, Hossein Baniasadi, Ahmad Ramazani, and Mohamadhasan Ansarizadeh. "Design and fabrication of conductive nanofibrous scaffolds for neural tissue engineering: Process modeling via response surface methodology." Journal of Biomaterials Applications 33, no. 5 (November 2018): 619–29. http://dx.doi.org/10.1177/0885328218808917.

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Peripheral nervous system in contrary to central one has the potential for regeneration, but its regrowth requires proper environmental conditions and supporting growth factors. The aim of this study is to design and fabricate a conductive polyaniline/graphene nanoparticles incorporated gelatin nanofibrous scaffolds suitable for peripheral nervous system regeneration. The scaffolds were fabricated with electrospinning and the fabrication process was designed with Design-Expert software via response surface methodology. The effect of process parameters including applied voltage (kV), syringe pump ﬂow rate (cm3/h), and PAG concentration (wt%), on the scaffold conductivity, nanofibers diameter, and cell viability were investigated. The obtained results showed that the scaffold conductivity and cell viability are affected by polyaniline/graphene concentration while nanofiber diameter is more affected by the applied voltage and syringe pump ﬂow rate. Optimum scaffold with maximum conductivity (0.031 ± 0.0013 S/cm) and cell compatibility and suitable diameter were electrospun according to the software introduced values for the process parameters (voltage of 13 kV, flow rate of 0.1 cm3/h, and PAG wt.% of 1.3) and its morphology, cell compatibility, and biodegradability were further investigated, which showed its potential for applying in peripheral nervous system injury regeneration.

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Antonova, Olga Y., Olga Y. Kochetkova, and Yuri M. Shlyapnikov. "ECM-Mimetic Nylon Nanofiber Scaffolds for Neurite Growth Guidance." Nanomaterials 11, no. 2 (February 18, 2021): 516. http://dx.doi.org/10.3390/nano11020516.

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Numerous nanostructured synthetic scaffolds mimicking the architecture of the natural extracellular matrix (ECM) have been described, but the polymeric nanofibers comprising the scaffold were substantially thicker than the natural collagen nanofibers of neural ECM. Here, we report neuron growth on electrospun scaffolds of nylon-4,6 fibers with an average diameter of 60 nm, which closely matches the diameter of collagen nanofibers of neural ECM, and compare their properties with the scaffolds of thicker 300 nm nanofibers. Previously unmodified nylon was not regarded as an independent nanostructured matrix for guided growth of neural cells; however, it is particularly useful for ultrathin nanofiber production. We demonstrate that, while both types of fibers stimulate directed growth of neuronal processes, ultrathin fibers are more efficient in promoting and accelerating neurite elongation. Both types of scaffolds also improved synaptogenesis and the formation of connections between hippocampal neurons; however, the mechanisms of interaction of neurites with the scaffolds were substantially different. While ultrathin fibers formed numerous weak immature β1-integrin-positive focal contacts localized over the entire cell surface, scaffolds of submicron fibers formed β1-integrin focal adhesions only on the cell soma. This indicates that the scaffold nanotopology can influence focal adhesion assembly involving various integrin subunits. The fabricated nanostructured scaffolds demonstrated high stability and resistance to biodegradation, as well as absence of toxic compound release after 1 month of incubation with live cells in vitro. Our results demonstrate the high potential of this novel type of nanofibers for clinical application as substrates facilitating regeneration of nervous tissue.

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Mammadov, Busra, Melike Sever, Mustafa O. Guler, and Ayse B. Tekinay. "Neural differentiation on synthetic scaffold materials." Biomaterials Science 1, no. 11 (2013): 1119. http://dx.doi.org/10.1039/c3bm60150a.

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Gao, Mingyong, Haiyin Tao, Tao Wang, Ailin Wei, and Bin He. "Functionalized self-assembly polypeptide hydrogel scaffold applied in modulation of neural progenitor cell behavior." Journal of Bioactive and Compatible Polymers 32, no. 1 (September 21, 2016): 45–60. http://dx.doi.org/10.1177/0883911516653146.

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Three-dimensional cell culturing provides an appealing biomimetic platform to probe the biological effects of a designed extracellular matrix on the behavior of seeded neural stem or neural progenitor cells. This culturing model serves as an important tool to investigate functional regulators involved in proliferation and differentiation of neural progenitor cells. This study aims to reconstruct a polypeptide hydrogel matrix functionally integrated with cyclo-RGD motif [c(RGDfK)] for initial exploration of neural progenitor cell behavior in three-dimensional culture. Three types of hydrogel scaffolds including Type I collagen, RADA16 self-assembly peptide, and RADA16-c(RGDfK) self-assembly peptide hydrogel were employed to serve as the culturing extracellular matrix of neonatal rat spinal neural progenitor cells. The neural adhesion of functionalized self-assembly peptide hydrogel was acquired prior to its RADA16 counterpart with neural progenitor cell seeding tests. The biophysiological properties of self-assembly peptide hydrogel scaffolds were then detected by scanning electron microscopy and rheology measurements. The biological behavior of embedded neural progenitor cells including cell proliferation and differentiation in three-dimensional niche were analyzed by MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)] tests and immunocytochemistry fluorescence staining. The 1% (w/v) RADA16-c(RGDfK) hydrogel scaffold [R16-c(RGDfK)HS] demonstrated an elastic modulus(312 ± 5.7 Pa) compatible with central neural cells, which significantly facilitated the proliferation of embedded neural progenitor cells. Compared to collagen hydrogel, both RADA16 and RADA16-c(RGDfK) hydrogel scaffold improved the cellular proliferation and neuronal differentiation of neural progenitor cells in a three-dimensional culture model. In order to model neuronal regeneration, introduction of neurotrophin-3 in the differentiation environment significantly increased the neuronal differentiation in which the ratio of Tuj-1-positive cell number increased to 72.5% ± 4.7% in the c(RGDfK)-functionalized three-dimensional matrix environment at 7 days in culture. Collectively, the present R16-c(RGDfK)HS displays excellent central neural biocompatibility and emerges as a promising bioengineered extracellular matrix niche of neural stem or progenitor cells, building a solid foundation for the subsequent in vitro and in vivo studies including neural repair, regeneration, and development.

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Zhao, Xinhao, Huiru Wang, Yunlong Zou, Weiwei Xue, Yang Zhuang, Rui Gu, He Shen, and Jianwu Dai. "Optimized, visible light-induced crosslinkable hybrid gelatin/hyaluronic acid scaffold promotes complete spinal cord injury repair." Biomedical Materials 17, no. 2 (January 25, 2022): 024104. http://dx.doi.org/10.1088/1748-605x/ac45ec.

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Abstract Severe microenvironmental changes after spinal cord injury (SCI) present serious challenges in neural regeneration and tissue repair. Gelatin (GL)- and hyaluronic acid (HA)-based hydrogels are attractive scaffolds because they are major components of the extracellular matrix and can provide a favorable adjustable microenvironment for neurogenesis and motor function recovery. In this study, three-dimensional hybrid GL/HA hydrogel scaffolds were prepared and optimized. The hybrid hydrogels could undergo in situ gelation and fit the defects perfectly via visible light-induced crosslinking in the complete SCI rats. We found that the transplantation of the hybrid hydrogel scaffold significantly reduced the inflammatory responses and suppressed glial scar formation in an HA concentration-dependent manner. Moreover, the hybrid hydrogel with GL/HA ratios less than 8/2 effectively promoted endogenous neural stem cell migration and neurogenesis, as well as improved neuron maturation and axonal regeneration. The results showed locomotor function improved 60 days after transplantation, thus suggesting that GL/HA hydrogels can be considered as a promising scaffold for complete SCI repair.

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Kondiah, Pariksha Jolene, Pierre P. D. Kondiah, Yahya E. Choonara, Thashree Marimuthu, and Viness Pillay. "A 3D Bioprinted Pseudo-Bone Drug Delivery Scaffold for Bone Tissue Engineering." Pharmaceutics 12, no. 2 (February 17, 2020): 166. http://dx.doi.org/10.3390/pharmaceutics12020166.

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A 3D bioprinted pseudo-bone drug delivery scaffold was fabricated to display matrix strength, matrix resilience, as well as porous morphology of healthy human bone. Computer-aided design (CAD) software was employed for developing the 3D bioprinted scaffold. Further optimization of the scaffold was undertaken using MATLAB® software and artificial neural networks (ANN). Polymers employed for formulating the 3D scaffold comprised of polypropylene fumarate (PPF), free radical polymerized polyethylene glycol- polycaprolactone (PEG-PCL-PEG), and pluronic (PF127). Simvastatin was incorporated into the 3D bioprinted scaffolds to further promote bone healing and repair properties. The 3D bioprinted scaffold was characterized for its chemical, morphological, mechanical, and in vitro release kinetics for evaluation of its behavior for application as an implantable scaffold at the site of bone fracture. The ANN-optimized 3D bioprinted scaffold displayed significant properties as a controlled release platform, demonstrating drug release over 20 days. The 3D bioprinted scaffold further displayed formation as a pseudo-bone matrix, using a human clavicle bone model, induced with a butterfly fracture. The strength of the pseudo-bone matrix, evaluated for its matrix hardness (MH) and matrix resilience (MR), was evaluated to be as strong as original bone, having a 99% MH and 98% MR property, to healthy human clavicle bones.

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Zaszczynska, Angelika, Paweł Sajkiewicz, and Arkadiusz Gradys. "Piezoelectric Scaffolds as Smart Materials for Neural Tissue Engineering." Polymers 12, no. 1 (January 8, 2020): 161. http://dx.doi.org/10.3390/polym12010161.

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Injury to the central or peripheral nervous systems leads to the loss of cognitive and/or sensorimotor capabilities, which still lacks an effective treatment. Tissue engineering in the post-injury brain represents a promising option for cellular replacement and rescue, providing a cell scaffold for either transplanted or resident cells. Tissue engineering relies on scaffolds for supporting cell differentiation and growth with recent emphasis on stimuli responsive scaffolds, sometimes called smart scaffolds. One of the representatives of this material group is piezoelectric scaffolds, being able to generate electrical charges under mechanical stimulation, which creates a real prospect for using such scaffolds in non-invasive therapy of neural tissue. This paper summarizes the recent knowledge on piezoelectric materials used for tissue engineering, especially neural tissue engineering. The most used materials for tissue engineering strategies are reported together with the main achievements, challenges, and future needs for research and actual therapies. This review provides thus a compilation of the most relevant results and strategies and serves as a starting point for novel research pathways in the most relevant and challenging open questions.

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Sirkkunan, Devindraan, Belinda Pingguan-Murphy, and Farina Muhamad. "Directing Axonal Growth: A Review on the Fabrication of Fibrous Scaffolds That Promotes the Orientation of Axons." Gels 8, no. 1 (December 28, 2021): 25. http://dx.doi.org/10.3390/gels8010025.

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Tissues are commonly defined as groups of cells that have similar structure and uniformly perform a specialized function. A lesser-known fact is that the placement of these cells within these tissues plays an important role in executing its functions, especially for neuronal cells. Hence, the design of a functional neural scaffold has to mirror these cell organizations, which are brought about by the configuration of natural extracellular matrix (ECM) structural proteins. In this review, we will briefly discuss the various characteristics considered when making neural scaffolds. We will then focus on the cellular orientation and axonal alignment of neural cells within their ECM and elaborate on the mechanisms involved in this process. A better understanding of these mechanisms could shed more light onto the rationale of fabricating the scaffolds for this specific functionality. Finally, we will discuss the scaffolds used in neural tissue engineering (NTE) and the methods used to fabricate these well-defined constructs.

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Osorio-Londoño, Diana María, José Rafael Godínez-Fernández, Ma Cristina Acosta-García, Juan Morales-Corona, Roberto Olayo-González, and Axayácatl Morales-Guadarrama. "Pyrrole Plasma Polymer-Coated Electrospun Scaffolds for Neural Tissue Engineering." Polymers 13, no. 22 (November 10, 2021): 3876. http://dx.doi.org/10.3390/polym13223876.

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Promising strategies for neural tissue engineering are based on the use of three-dimensional substrates for cell anchorage and tissue development. In this work, fibrillar scaffolds composed of electrospun randomly- and aligned-oriented fibers coated with plasma synthesized pyrrole polymer, doped and undoped with iodine, were fabricated and characterized. Infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction analysis revealed the functional groups and molecular integration of each scaffold, as well as the effect of plasma polymer synthesis on crystallinity. Scanning microscopy imaging demonstrated the porous fibrillar micrometric structure of the scaffolds, which afforded adhesion, infiltration, and survival for the neural cells. Orientation analysis of electron microscope images confirmed the elongation of neurite-like cell structures elicited by undoped plasma pyrrole polymer-coated aligned scaffolds, without any biochemical stimuli. The MTT colorimetric assay validated the biocompatibility of the fabricated composite materials, and further evidenced plasma pyrrole polymer-coated aligned scaffolds as permissive substrates for the support of neural cells. These results suggest plasma synthesized pyrrole polymer-coated aligned scaffolds are promising materials for tissue engineering applications.

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Zoughaib, Mohamed, Kenana Dayob, Svetlana Avdokushina, Marat I. Kamalov, Diana V. Salakhieva, Irina N. Savina, Igor A. Lavrov, and Timur I. Abdullin. "Oligo (Poly(Ethylene Glycol)Fumarate)-Based Multicomponent Cryogels for Neural Tissue Replacement." Gels 9, no. 2 (January 25, 2023): 105. http://dx.doi.org/10.3390/gels9020105.

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Synthetic hydrogels provide a promising platform to produce neural tissue analogs with improved control over structural, physical, and chemical properties. In this study, oligo(poly(ethylene glycol) fumarate) (OPF)-based macroporous cryogels were developed as a potential next-generation alternative to a non-porous OPF hydrogel previously proposed as an advanced biodegradable scaffold for spinal cord repair. A series of OPF cryogel conduits in combination with PEG diacrylate and 2-(methacryloyloxy) ethyl-trimethylammonium chloride (MAETAC) cationic monomers were synthesized and characterized. The contribution of each component to viscoelastic and hydration behaviors and porous structure was identified, and concentration relationships for these properties were revealed. The rheological properties of the materials corresponded to those of neural tissues and scaffolds, according to the reviewed data. A comparative assessment of adhesion, migration, and proliferation of neuronal cells in multicomponent cryogels was carried out to optimize cell-supporting characteristics. The results show that OPF-based cryogels can be used as a tunable synthetic scaffold for neural tissue repair with advantages over their hydrogel counterparts.

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Agbay, Andrew, John M. Edgar, Meghan Robinson, Tara Styan, Krista Wilson, Julian Schroll, Junghyuk Ko, Nima Khadem Mohtaram, Martin Byung-Guk Jun, and Stephanie M. Willerth. "Biomaterial Strategies for Delivering Stem Cells as a Treatment for Spinal Cord Injury." Cells Tissues Organs 202, no. 1-2 (2016): 42–51. http://dx.doi.org/10.1159/000446474.

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Ongoing clinical trials are evaluating the use of stem cells as a way to treat traumatic spinal cord injury (SCI). However, the inhibitory environment present in the injured spinal cord makes it challenging to achieve the survival of these cells along with desired differentiation into the appropriate phenotypes necessary to regain function. Transplanting stem cells along with an instructive biomaterial scaffold can increase cell survival and improve differentiation efficiency. This study reviews the literature discussing different types of instructive biomaterial scaffolds developed for transplanting stem cells into the injured spinal cord. We have chosen to focus specifically on biomaterial scaffolds that direct the differentiation of neural stem cells and pluripotent stem cells since they offer the most promise for producing the cell phenotypes that could restore function after SCI. In terms of biomaterial scaffolds, this article reviews the literature associated with using hydrogels made from natural biomaterials and electrospun scaffolds for differentiating stem cells into neural phenotypes. It then presents new data showing how these different types of scaffolds can be combined for neural tissue engineering applications and provides directions for future studies.

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Mahmood, Asim, Hongtao Wu, Changsheng Qu, Selina Mahmood, Ye Xiong, David L. Kaplan, and Michael Chopp. "Suppression of neurocan and enhancement of axonal density in rats after treatment of traumatic brain injury with scaffolds impregnated with bone marrow stromal cells." Journal of Neurosurgery 120, no. 5 (May 2014): 1147–55. http://dx.doi.org/10.3171/2013.12.jns131362.

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Object Neurocan is a major form of growth-inhibitory molecule (growth-IM) that suppresses axonal regeneration after neural injury. Bone marrow stromal cells (MSCs) have been shown to inhibit neurocan expression in vitro and in animal models of cerebral ischemia. Therefore, the present study was designed to investigate the effects of treatment of MSCs impregnated with collagen scaffolds on neurocan expression after traumatic brain injury (TBI). Methods Adult male Wistar rats were injured with controlled cortical impact and treated with saline, human MSCs (hMSCs) (3 × 106) alone, or hMSCs (3 × 106) impregnated into collagen scaffolds (scaffold + hMSCs) transplanted into the lesion cavity 7 days after TBI (20 rats per group). Rats were sacrificed 14 days after TBI, and brain tissues were harvested for immunohistochemical studies, Western blot analyses, laser capture microdissections, and quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) to evaluate neurocan protein and gene expressions after various treatments. Results Animals treated with scaffold + hMSCs after TBI showed increased axonal and synaptic densities compared with the other groups. Scaffold + hMSC treatment was associated with reduced TBI-induced neurocan protein expression and upregulated growth-associated protein 43 (GAP-43) and synaptophysin expression in the lesion boundary zone. In addition, animals in the scaffold + hMSC group had decreased neurocan transcription in reactive astrocytes after TBI. Reduction of neurocan expression was significantly greater in the scaffold + hMSC group than in the group treated with hMSCs alone. Conclusions The results of this study show that transplanting hMSCs with scaffolds enhances the effect of hMSCs on axonal plasticity in TBI rats. This enhanced axonal plasticity may partially be attributed to the downregulation of neurocan expression by hMSC treatment after injury.

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Altun, Esra, Mehmet O. Aydogdu, Sine O. Togay, Ahmet Z. Sengil, Nazmi Ekren, Merve E. Haskoylu, Ebru T. Oner, et al. "Bioinspired scaffold induced regeneration of neural tissue." European Polymer Journal 114 (May 2019): 98–108. http://dx.doi.org/10.1016/j.eurpolymj.2019.02.008.

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Ceyssens, Frederik, Kris van Kuyck, Greetje Vande Velde, Marleen Welkenhuysen, Linda Stappers, Bart Nuttin, and Robert Puers. "Resorbable scaffold based chronic neural electrode arrays." Biomedical Microdevices 15, no. 3 (February 16, 2013): 481–93. http://dx.doi.org/10.1007/s10544-013-9748-x.

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Wong, Darice Y., Paul H. Krebsbach, and Scott J. Hollister. "Brain cortex regeneration affected by scaffold architectures." Journal of Neurosurgery 109, no. 4 (October 2008): 715–22. http://dx.doi.org/10.3171/jns/2008/109/10/0715.

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Object The aim of this study was to compare designed scaffolds with a random-pored sponge scaffold to determine what role scaffold architecture plays in a cortical injury model. Methods Cylindrical scaffolds (3 × 3 mm) were made of a poly-(ε-caprolactone) polymer with 2 different molds from a 3D printer and had either: 1) unidirectional channels and microgrooves oriented longitudinally within the cylinder or 2) orthogonally intersecting channels and axial microgrooves within the cylinder. Additional randomized porosity was imparted using a salt-leaching method. A control scaffold without channels or microgrooves but containing random pores was also made. Scaffolds were implanted for 1, 4, and 8 weeks in a cylindrical defect created 3 mm posterior to the bregma in rat cortex. Control animals had tissue removed but received no implant. Brains were coronally cryosectioned and sections were stained. Antibodies for nestin, glial fibrillary acidic protein (GFAP), and TUJ1 were used to identify neural progenitors, activated astrocytes, and neuronal axons. Tissue ingrowth (H & E), astrocytic infiltration (GFAP), parenchymal inflammation (GFAP), and defect width (H & E) were quantified from images. Results Defect widths grew and parenchymal inflammation decreased over time with no statistical difference between groups. Total tissue ingrowth and astrocytic infiltration increased over time and was greatest in the orthogonal design group. Specific cell ingrowth, which was aligned with microgrooves interiorly in the orthogonal group and exteriorly in the longitudinal channel group, was qualitatively assessed from nestin and TUJ1 labeling. Conclusions Scaffold architecture can benefit brain tissue regeneration by integrating the following design principles: 1) large (100s of micrometers) pores or channels oriented toward the parenchyma for increased astrocytic infiltration; 2) microgrooves oriented in the desired direction of cellular migration and neuronal alignment; and 3) fully interconnecting channels for cellular migration and tissue integration.

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Cassimjee, Henna, Pradeep Kumar, Philemon Ubanako, and Yahya E. Choonara. "Genipin-Crosslinked, Proteosaccharide Scaffolds for Potential Neural Tissue Engineering Applications." Pharmaceutics 14, no. 2 (February 18, 2022): 441. http://dx.doi.org/10.3390/pharmaceutics14020441.

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Traumatic brain injuries (TBIs) are still a challenge for the field of modern medicine. Many treatment options such as autologous grafts and stem cells show limited promise for the treatment and the reversibility of damage caused by TBIs. Injury beyond the critical size necessitates the implementation of scaffolds that function as surrogate extracellular matrices. Two scaffolds were synthesised utilising polysaccharides, chitosan and hyaluronic acid in conjunction with gelatin. Both scaffolds were chemically crosslinked using a naturally derived crosslinker, Genipin. The polysaccharides increased the mechanical strength of each scaffold, while gelatin provided the bioactive sequence, which promoted cellular interactions. The effect of crosslinking was investigated, and the crosslinked hydrogels showed higher thermal decomposition temperatures, increased resistance to degradation, and pore sizes ranging from 72.789 ± 16.85 µm for the full interpenetrating polymer networks (IPNs) and 84.289 ± 7.658 μm for the semi-IPN. The scaffolds were loaded with Dexamethasone-21-phosphate to investigate their efficacy as a drug delivery vehicle, and the full IPN showed a 100% release in 10 days, while the semi-IPN showed a burst release in 6 h. Both scaffolds stimulated the proliferation of rat pheochromocytoma (PC12) and human glioblastoma multiforme (A172) cell cultures and also provided signals for A172 cell migration. Both scaffolds can be used as potential drug delivery vehicles and as artificial extracellular matrices for potential neural regeneration.

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Gerschenfeld, Gaspard, Rachida Aid, Teresa Simon-Yarza, Soraya Lanouar, Patrick Charnay, Didier Letourneur, and Piotr Topilko. "Tuning Physicochemical Properties of a Macroporous Polysaccharide-Based Scaffold for 3D Neuronal Culture." International Journal of Molecular Sciences 22, no. 23 (November 25, 2021): 12726. http://dx.doi.org/10.3390/ijms222312726.

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Central nervous system (CNS) lesions are a leading cause of death and disability worldwide. Three-dimensional neural cultures in biomaterials offer more physiologically relevant models for disease studies, toxicity screenings or in vivo transplantations. Herein, we describe the development and use of pullulan/dextran polysaccharide-based scaffolds for 3D neuronal culture. We first assessed scaffolding properties upon variation of the concentration (1%, 1.5%, 3% w/w) of the cross-linking agent, sodium trimetaphosphate (STMP). The lower STMP concentration (1%) allowed us to generate scaffolds with higher porosity (59.9 ± 4.6%), faster degradation rate (5.11 ± 0.14 mg/min) and lower elastic modulus (384 ± 26 Pa) compared with 3% STMP scaffolds (47 ± 2.1%, 1.39 ± 0.03 mg/min, 916 ± 44 Pa, respectively). Using primary cultures of embryonic neurons from PGKCre, Rosa26tdTomato embryos, we observed that in 3D culture, embryonic neurons remained in aggregates within the scaffolds and did not attach, spread or differentiate. To enhance neuronal adhesion and neurite outgrowth, we then functionalized the 1% STMP scaffolds with laminin. We found that treatment of the scaffold with a 100 μg/mL solution of laminin, combined with a subsequent freeze-drying step, created a laminin mesh network that significantly enhanced embryonic neuron adhesion, neurite outgrowth and survival. Such scaffold therefore constitutes a promising neuron-compatible and biodegradable biomaterial.

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Yeh, Jue-Zong, Ding-Han Wang, Juin-Hong Cherng, Yi-Wen Wang, Gang-Yi Fan, Nien-Hsien Liou, Jiang-Chuan Liu, and Chung-Hsing Chou. "A Collagen-Based Scaffold for Promoting Neural Plasticity in a Rat Model of Spinal Cord Injury." Polymers 12, no. 10 (September 29, 2020): 2245. http://dx.doi.org/10.3390/polym12102245.

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In spinal cord injury (SCI) therapy, glial scarring formed by activated astrocytes is a primary problem that needs to be solved to enhance axonal regeneration. In this study, we developed and used a collagen scaffold for glial scar replacement to create an appropriate environment in an SCI rat model and determined whether neural plasticity can be manipulated using this approach. We used four experimental groups, as follows: SCI-collagen scaffold, SCI control, normal spinal cord-collagen scaffold, and normal control. The collagen scaffold showed excellent in vitro and in vivo biocompatibility. Immunofluorescence staining revealed increased expression of neurofilament and fibronectin and reduced expression of glial fibrillary acidic protein and anti-chondroitin sulfate in the collagen scaffold-treated SCI rats at 1 and 4 weeks post-implantation compared with that in untreated SCI control. This indicates that the collagen scaffold implantation promoted neuronal survival and axonal growth within the injured site and prevented glial scar formation by controlling astrocyte production for their normal functioning. Our study highlights the feasibility of using the collagen scaffold in SCI repair. The collagen scaffold was found to exert beneficial effects on neuronal activity and may help in manipulating synaptic plasticity, implying its great potential for clinical application in SCI.

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Gu, Ben Jiahe, Dennis Jgamadze, Guoming (Tony) Man, and Han-Chiao Isaac Chen. "4418 Optimization and Validation of a Silk Scaffold-Based Neural Tissue Construct." Journal of Clinical and Translational Science 4, s1 (June 2020): 13–14. http://dx.doi.org/10.1017/cts.2020.85.

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OBJECTIVES/GOALS: Our goal is to develop a silk fibroin scaffold-based neural tissue construct and characterize it in a rat model of cortical injury. We aim to optimize the construct for transplantation, test pharmacologic interventions that may enhance its survival, and evaluate its integration with the host brain. METHODS/STUDY POPULATION: To optimize cell density and health, silk fibroin scaffolds varying in porosity and stiffness were seeded with E18 GFP+ rat cortical neurons and imaged at DIV 5. Different seeding methods and loads were similarly tested. Constructs, loaded with an inhibitor of apoptosis (ROCK inhibitor Y-27632) or necroptosis (necrostatin-1) in a fibrin hydrogel, were transplanted into aspiration lesions created in the primary motor cortex of Sprague-Dawley rats, and graft survival was compared to negative control at 2 weeks. Lastly, constructs were transplanted and evaluated via immunohistochemistry at 1, 2, and 4-month time points for survival, differentiation, inflammation, and anatomic integration. RESULTS/ANTICIPATED RESULTS: Scaffolds with smaller pore sizes retained more cells after seeding. Softer scaffolds, which enhance hemostasis at transplantation, did not compromise cell health on live/dead assay. We anticipate that seeding concentrated cell suspensions onto multiple surfaces of the construct will produce the most evenly seeded and cell-dense constructs. Based on a prior pilot study, we anticipate that necrostatin-1 will significantly improve intermediate-term construct survival. We have observed up to 15% cell survival at 1 month with retained neuronal identity and abundant axonal projections into the brain despite evidence of persistent inflammation; we anticipate similar outcomes at later time points. DISCUSSION/SIGNIFICANCE OF IMPACT: Our construct, due to its exceptional longevity in vitro, manipulability, and modularity, is an attractive platform for neural tissue engineering. In the present work, we optimize and validate this technology for transplantation with the goal of addressing the morbidity burden of cortical injury.

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Liu, Xi, Shumeng Bai, and Huijing Zhao. "Silk Fibroin-Based Scaffold for Neural Tissue Engineering." Journal of Biomaterials and Tissue Engineering 4, no. 12 (December 1, 2014): 1012–18. http://dx.doi.org/10.1166/jbt.2014.1254.

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King, Jasmine L., Panita Maturavongsadit, Shawn D. Hingtgen, and S. Rahima Benhabbour. "Injectable pH Thermo-Responsive Hydrogel Scaffold for Tumoricidal Neural Stem Cell Therapy for Glioblastoma Multiforme." Pharmaceutics 14, no. 10 (October 20, 2022): 2243. http://dx.doi.org/10.3390/pharmaceutics14102243.

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Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults and despite recent advances in treatment modalities, GBM remains incurable. Injectable hydrogel scaffolds are a versatile delivery system that can improve delivery of drug and cell therapeutics for GBM. In this report, we investigated an injectable nanocellulose/chitosan-based hydrogel scaffold for neural stem cell encapsulation and delivery. Hydrogels were prepared using thermogelling beta-glycerophosphate (BGP) and hydroxyethyl cellulose (HEC), chitosan (CS), and cellulose nanocrystals (CNCs). We evaluated the impact of neural stem cells on hydrogel gelation kinetics, microstructures, and degradation. Furthermore, we investigated the biomaterial effects on cell viability and functionality. We demonstrated that the incorporation of cells at densities of 1, 5 and 10 million does not significantly impact rheological and physical properties CS scaffolds. However, addition of CNCs significantly prolonged hydrogel degradation when cells were seeded at 5 and 10 million per 1 mL hydrogel. In vitro cell studies demonstrated high cell viability, release of TRAIL at therapeutic concentrations, and effective tumor cell killing within 72 h. The ability of these hydrogel scaffolds to support stem cell encapsulation and viability and maintain stem cell functionality makes them an attractive cell delivery system for local treatment of post-surgical cancers.

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Wang, Shuping, Changkai Sun, Shui Guan, Wenfang Li, Jianqiang Xu, Dan Ge, Meiling Zhuang, Tianqing Liu, and Xuehu Ma. "Chitosan/gelatin porous scaffolds assembled with conductive poly(3,4-ethylenedioxythiophene) nanoparticles for neural tissue engineering." Journal of Materials Chemistry B 5, no. 24 (2017): 4774–88. http://dx.doi.org/10.1039/c7tb00608j.

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Chi, Jiayu, Mingyue Wang, Jialin Chen, Lizhi Hu, Zhixuan Chen, Ludvig J. Backman, and Wei Zhang. "Topographic Orientation of Scaffolds for Tissue Regeneration: Recent Advances in Biomaterial Design and Applications." Biomimetics 7, no. 3 (September 12, 2022): 131. http://dx.doi.org/10.3390/biomimetics7030131.

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Tissue engineering to develop alternatives for the maintenance, restoration, or enhancement of injured tissues and organs is gaining more and more attention. In tissue engineering, the scaffold used is one of the most critical elements. Its characteristics are expected to mimic the native extracellular matrix and its unique topographical structures. Recently, the topographies of scaffolds have received increasing attention, not least because different topographies, such as aligned and random, have different repair effects on various tissues. In this review, we have focused on various technologies (electrospinning, directional freeze-drying, magnetic freeze-casting, etching, and 3-D printing) to fabricate scaffolds with different topographic orientations, as well as discussed the physicochemical (mechanical properties, porosity, hydrophilicity, and degradation) and biological properties (morphology, distribution, adhesion, proliferation, and migration) of different topographies. Subsequently, we have compiled the effect of scaffold orientation on the regeneration of vessels, skin, neural tissue, bone, articular cartilage, ligaments, tendons, cardiac tissue, corneas, skeletal muscle, and smooth muscle. The compiled information in this review will facilitate the future development of optimal topographical scaffolds for the regeneration of certain tissues. In the majority of tissues, aligned scaffolds are more suitable than random scaffolds for tissue repair and regeneration. The underlying mechanism explaining the various effects of aligned and random orientation might be the differences in “contact guidance”, which stimulate certain biological responses in cells.

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Tonellato, Marika, Monica Piccione, Matteo Gasparotto, Pietro Bellet, Lucia Tibaudo, Nicola Vicentini, Elisabetta Bergantino, et al. "Commitment of Autologous Human Multipotent Stem Cells on Biomimetic Poly-L-Lactic Acid-Based Scaffolds Is Strongly Influenced by Structure and Concentration of Carbon Nanomaterial." Nanomaterials 10, no. 3 (February 27, 2020): 415. http://dx.doi.org/10.3390/nano10030415.

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Nanocomposite scaffolds combining carbon nanomaterials (CNMs) with a biocompatible matrix are able to favor the neuronal differentiation and growth of a number of cell types, because they mimic neural-tissue nanotopography and/or conductivity. We performed comparative analysis of biomimetic scaffolds with poly-L-lactic acid (PLLA) matrix and three different p-methoxyphenyl functionalized carbon nanofillers, namely, carbon nanotubes (CNTs), carbon nanohorns (CNHs), and reduced graphene oxide (RGO), dispersed at varying concentrations. qRT-PCR analysis of the modulation of neuronal markers in human circulating multipotent cells cultured on nanocomposite scaffolds showed high variability in their expression patterns depending on the scaffolds’ inhomogeneities. Local stimuli variation could result in a multi- to oligopotency shift and commitment towards multiple cell lineages, which was assessed by the qRT-PCR profiling of markers for neural, adipogenic, and myogenic cell lineages. Less conductive scaffolds, i.e., bare poly-L-lactic acid (PLLA)-, CNH-, and RGO-based nanocomposites, appeared to boost the expression of myogenic-lineage marker genes. Moreover, scaffolds are much more effective on early commitment than in subsequent differentiation. This work suggests that biomimetic PLLA carbon-nanomaterial (PLLA-CNM) scaffolds combined with multipotent autologous cells can represent a powerful tool in the regenerative medicine of multiple tissue types, opening the route to next analyses with specific and standardized scaffold features.

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Wang, Xiumei, Jin He, Ying Wang, and Fu-Zhai Cui. "Hyaluronic acid-based scaffold for central neural tissue engineering." Interface Focus 2, no. 3 (March 21, 2012): 278–91. http://dx.doi.org/10.1098/rsfs.2012.0016.

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Central nervous system (CNS) regeneration with central neuronal connections and restoration of synaptic connections has been a long-standing worldwide problem and, to date, no effective clinical therapies are widely accepted for CNS injuries. The limited regenerative capacity of the CNS results from the growth-inhibitory environment that impedes the regrowth of axons. Central neural tissue engineering has attracted extensive attention from multi-disciplinary scientists in recent years, and many studies have been carried out to develop cell- and regeneration-activating biomaterial scaffolds that create an artificial micro-environment suitable for axonal regeneration. Among all the biomaterials, hyaluronic acid (HA) is a promising candidate for central neural tissue engineering because of its unique physico-chemical and biological properties. This review attempts to outline current biomaterials-based strategies for CNS regeneration from a tissue engineering point of view and discusses the main progresses in research of HA-based scaffolds for central neural tissue engineering in detail.

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Finch, L., S. Harris, C. Adams, J. Sen, J. Tickle, N. Tzerakis, and DM Chari. "WP1-22 DuraGen™ as an encapsulating material for neural stem cell delivery." Journal of Neurology, Neurosurgery & Psychiatry 90, no. 3 (February 14, 2019): e7.2-e7. http://dx.doi.org/10.1136/jnnp-2019-abn.22.

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ObjectivesAchieving neural regeneration after spinal cord injury (SCI) represents a significant challenge. Neural stem cell (NSC) therapy offers replacement of damaged cells and delivery of pro-regenerative factors, but >95% of cells die when transplanted to sites of neural injury. Biomaterial scaffolds provide cellular protective encapsulation to improve cell survival. However, current available scaffolds are overwhelmingly not approved for human use, presenting a major barrier to clinical translation. Surgical biomaterials offer the unique benefit of being FDA-approved for human implantation. Specifically, a neurosurgical grade material, DuraGen™, used predominantly for human duraplasty has many attractive features of an ideal biomaterial scaffold. Here, we have investigated the use of DuraGen™ as a 3D cell encapsulation device for potential use in combinatorial, regenerative therapies.MethodsPrimary NSCs were seeded into optimised sheets of DuraGen™. NSC growth and fate within DuraGen™ were assessed using 3D microscopic fluorescence imaging techniques.ResultsDuraGen™ supports the survival (ca 95% viability, 12 days) and 3D growth of NSCs. NSC phenotype, proliferative capacity and differentiation into astrocytes, neurons and oligodendrocytes were unaffected by DuraGen™.ConclusionsA ‘combinatorial therapy’, consisting of NSCs protected within a DuraGen™ matrix, offers a potential clinically translatable approach for neural cell therapy.

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Wang, Yifan, Sunčica Čanić, Martina Bukač, Charles Blaha, and Shuvo Roy. "Mathematical and Computational Modeling of Poroelastic Cell Scaffolds Used in the Design of an Implantable Bioartificial Pancreas." Fluids 7, no. 7 (July 1, 2022): 222. http://dx.doi.org/10.3390/fluids7070222.

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We present a multi-scale mathematical model and a novel numerical solver to study blood plasma flow and oxygen concentration in a prototype model of an implantable Bioartificial Pancreas (iBAP) that operates under arteriovenous pressure differential without the need for immunosuppressive therapy. The iBAP design consists of a poroelastic cell scaffold containing the healthy transplanted cells, encapsulated between two semi-permeable nano-pore size membranes to prevent the patient’s own immune cells from attacking the transplant. The device is connected to the patient’s vascular system via an anastomosis graft bringing oxygen and nutrients to the transplanted cells of which oxygen is the limiting factor for long-term viability. Mathematically, we propose a (nolinear) fluid–poroelastic structure interaction model to describe the flow of blood plasma through the scaffold containing the cells, and a set of (nonlinear) advection–reaction–diffusion equations defined on moving domains to study oxygen supply to the cells. These macro-scale models are solved using finite element method based solvers. One of the novelties of this work is the design of a novel second-order accurate fluid–poroelastic structure interaction solver, for which we prove that it is unconditionally stable. At the micro/nano-scale, Smoothed Particle Hydrodynamics (SPH) simulations are used to capture the micro/nano-structure (architecture) of cell scaffolds and obtain macro-scale parameters, such as hydraulic conductivity/permeability, from the micro-scale scaffold-specific architecture. To avoid expensive micro-scale simulations based on SPH simulations for every new scaffold architecture, we use Encoder–Decoder Convolution Neural Networks. Based on our numerical simulations, we propose improvements in the current prototype design. For example, we show that highly elastic scaffolds have a higher capacity for oxygen transfer, which is an important finding considering that scaffold elasticity can be controlled during their fabrication, and that elastic scaffolds improve cell viability. The mathematical and computational approaches developed in this work provide a benchmark tool for computational analysis of not only iBAP, but also, more generally, of cell encapsulation strategies used in the design of devices for cell therapy and bio-artificial organs.

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Borhani-Haghighi, Maryam, Shahnaz Razavi, and Zahra Khosravizadeh. "The Application of Alginate Scaffold in Neural Tissue Engineering." Neuroscience Journal of Shefaye Khatam 5, no. 4 (October 1, 2017): 76–86. http://dx.doi.org/10.18869/acadpub.shefa.5.4.76.

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Alhosseini, Sanaz Naghavi, Fathollah Moztarzadeh, and Akbar Karkhaneh. "Genipin-cross-linked poly(vinyl alcohol) for neural scaffold." Bioinspired, Biomimetic and Nanobiomaterials 6, no. 4 (December 2017): 191–98. http://dx.doi.org/10.1680/jbibn.16.00043.

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Wang, Yuting, Yanping Zhang, Zhongyang Zhang, Yingchun Su, Zegao Wang, Mingdong Dong, and Menglin Chen. "An injectable high-conductive bimaterial scaffold for neural stimulation." Colloids and Surfaces B: Biointerfaces 195 (November 2020): 111210. http://dx.doi.org/10.1016/j.colsurfb.2020.111210.

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Layrolle, Pierre, Pierre Payoux, and Stéphane Chavanas. "Message in a Scaffold: Natural Biomaterials for Three-Dimensional (3D) Bioprinting of Human Brain Organoids." Biomolecules 13, no. 1 (December 22, 2022): 25. http://dx.doi.org/10.3390/biom13010025.

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Brain organoids are invaluable tools for pathophysiological studies or drug screening, but there are still challenges to overcome in making them more reproducible and relevant. Recent advances in three-dimensional (3D) bioprinting of human neural organoids is an emerging approach that may overcome the limitations of self-organized organoids. It requires the development of optimal hydrogels, and a wealth of research has improved our knowledge about biomaterials both in terms of their intrinsic properties and their relevance on 3D culture of brain cells and tissue. Although biomaterials are rarely biologically neutral, few articles have reviewed their roles on neural cells. We here review the current knowledge on unmodified biomaterials amenable to support 3D bioprinting of neural organoids with a particular interest in their impact on cell homeostasis. Alginate is a particularly suitable bioink base for cell encapsulation. Gelatine is a valuable helper agent for 3D bioprinting due to its viscosity. Collagen, fibrin, hyaluronic acid and laminin provide biological support to adhesion, motility, differentiation or synaptogenesis and optimize the 3D culture of neural cells. Optimization of specialized hydrogels to direct differentiation of stem cells together with an increased resolution in phenotype analysis will further extend the spectrum of possible bioprinted brain disease models.

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Bian, Yuemin, and Xiang-Qun Xie. "Artificial Intelligent Deep Learning Molecular Generative Modeling of Scaffold-Focused and Cannabinoid CB2 Target-Specific Small-Molecule Sublibraries." Cells 11, no. 5 (March 7, 2022): 915. http://dx.doi.org/10.3390/cells11050915.

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Design and generation of high-quality target- and scaffold-specific small molecules is an important strategy for the discovery of unique and potent bioactive drug molecules. To achieve this goal, authors have developed the deep-learning molecule generation model (DeepMGM) and applied it for the de novo molecular generation of scaffold-focused small-molecule libraries. In this study, a recurrent neural network (RNN) using long short-term memory (LSTM) units was trained with drug-like molecules to result in a general model (g-DeepMGM). Sampling practices on indole and purine scaffolds illustrate the feasibility of creating scaffold-focused chemical libraries based on machine intelligence. Subsequently, a target-specific model (t-DeepMGM) for cannabinoid receptor 2 (CB2) was constructed following the transfer learning process of known CB2 ligands. Sampling outcomes can present similar properties to the reported active molecules. Finally, a discriminator was trained and attached to the DeepMGM to result in an in silico molecular design-test circle. Medicinal chemistry synthesis and biological validation was performed to further investigate the generation outcome, showing that XIE9137 was identified as a potential allosteric modulator of CB2. This study demonstrates how recent progress in deep learning intelligence can benefit drug discovery, especially in de novo molecular design and chemical library generation.

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Shendi, Dalia, Ana Dede, Yuan Yin, Chaoming Wang, Chandra Valmikinathan, and Anjana Jain. "Tunable, bioactive protein conjugated hyaluronic acid hydrogel for neural engineering applications." Journal of Materials Chemistry B 4, no. 16 (2016): 2803–18. http://dx.doi.org/10.1039/c5tb02235e.

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Naghashzargar, Elham, Dariush Semnani, and Saeed Karbasi. "Improving the Mechanical Properties of Wire-Rope Silk Scaffold by Artificial Neural Network in Tendon and Ligament Tissue Engineering." Journal of Engineered Fibers and Fabrics 10, no. 3 (September 2015): 155892501501000. http://dx.doi.org/10.1177/155892501501000303.

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Finding an appropriate model to assess and evaluate mechanical properties in tissue engineered scaffolds is a challenging issue. In this research, a structurally based model was applied to analyze the mechanics of engineered tendon and ligament. Major attempts were made to find the optimum mechanical properties of silk wire-rope scaffold by using the back propagation artificial neural network (ANN) method. Different samples of wire-rope scaffolds were fabricated according to Taguchi experimental design. The number of filaments and twist in each layer of the four layered wire-rope silk yarn were considered as the input parameters in the model. The output parameters included the mechanical properties which consisted of UTS, elongation at break, and stiffness. Finally, sensitivity analysis on input data showed that the number of filaments and the number of twists in the fourth layer are less important than other input parameters.

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Grossemy, Simon, Peggy P. Y. Chan, and Pauline M. Doran. "Electrical stimulation of cell growth and neurogenesis using conductive and nonconductive microfibrous scaffolds." Integrative Biology 11, no. 6 (June 1, 2019): 264–79. http://dx.doi.org/10.1093/intbio/zyz022.

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Abstract The effect of exogenous electrical stimulation on cell viability, attachment, growth, and neurogenesis was examined using PC12 cells in microfibrous viscose-rayon scaffolds immersed in culture medium. The scaffolds were applied either in their nonconductive state or after coating the fibres with 200 nm of gold to give a scaffold sheet resistivity of (13 ± 1.3) Ω square−1. The cells were treated for 12 days using direct current electrical stimulation of 2 h per day. No cytotoxic effects were observed when up to 500 mV (8.3 mV mm−1) was applied to the scaffolds without gold, or when up to 100 mV (1.7 mV mm−1) was applied to the scaffolds with gold. Compared with unstimulated cells, whereas electrical stimulation significantly enhanced cell growth and attachment in the nonconductive scaffolds without gold, similar effects were not found for the conductive scaffolds with gold. Neural differentiation in the presence of nerve growth factor was improved by electrical stimulation in both scaffolds; however, neurite development and the expression of key differentiation markers were greater in the nonconductive scaffolds without gold than in the scaffolds with gold. Application of the same current to scaffolds with and without gold led to much higher levels of neurogenesis in the scaffolds without gold. This work demonstrates that substantial benefits in terms of cell growth and neural differentiation can be obtained using electric fields exerted across nonconductive microfibrous scaffolds, and that this approach to electrical stimulation can be more effective than when the stimulus is applied to cells on conductive scaffolds.

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Mungenast, Lena, Fabian Züger, Jasmin Selvi, Ana Bela Faia-Torres, Jürgen Rühe, Laura Suter-Dick, and Maurizio R. Gullo. "Directional Submicrofiber Hydrogel Composite Scaffolds Supporting Neuron Differentiation and Enabling Neurite Alignment." International Journal of Molecular Sciences 23, no. 19 (September 29, 2022): 11525. http://dx.doi.org/10.3390/ijms231911525.

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Cell cultures aiming at tissue regeneration benefit from scaffolds with physiologically relevant elastic moduli to optimally trigger cell attachment, proliferation and promote differentiation, guidance and tissue maturation. Complex scaffolds designed with guiding cues can mimic the anisotropic nature of neural tissues, such as spinal cord or brain, and recall the ability of human neural progenitor cells to differentiate and align. This work introduces a cost-efficient gelatin-based submicron patterned hydrogel–fiber composite with tuned stiffness, able to support cell attachment, differentiation and alignment of neurons derived from human progenitor cells. The enzymatically crosslinked gelatin-based hydrogels were generated with stiffnesses from 8 to 80 kPa, onto which poly(ε-caprolactone) (PCL) alignment cues were electrospun such that the fibers had a preferential alignment. The fiber–hydrogel composites with a modulus of about 20 kPa showed the strongest cell attachment and highest cell proliferation, rendering them an ideal differentiation support. Differentiated neurons aligned and bundled their neurites along the aligned PCL filaments, which is unique to this cell type on a fiber–hydrogel composite. This novel scaffold relies on robust and inexpensive technology and is suitable for neural tissue engineering where directional neuron alignment is required, such as in the spinal cord.

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Kim, Dong Hwan, Bo Young Kim, Dong Hyun Kim, Jin Hur, and Chung-Hwan Baek. "Rabbit palatum-derived mesenchymal progenitor cells tri-lineage differentiation on 2D substrates and 3D printed constructs." Journal of Applied Biomaterials & Functional Materials 17, no. 3 (July 2019): 228080001983452. http://dx.doi.org/10.1177/2280800019834520.

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Hard palate, developed by embryo neural crest stem cells, is a tissue with strong regenerative abilities. It is considered an abundant source of progenitor cells, forming various mesenchymal tissues. Rabbits are more suitable models than murine animals for regenerative preclinical study of the head and neck, owing to their larger size. However, there are no reports of the existence or characteristics of neural crest stem cells in the hard palate of rabbits. In this study, we demonstrate for the first time the presence of nestin-, Sox2-, and p75-positive neural crest stem cells obtained from the hard palate of rabbits and the properties of these cells. Flow cytometry analysis revealed that CD29, CD44, and CD81 were positive; and CD11b, CD34, and CD90 were negative on the ex vivo expanded palatal progenitor cells. Finally, we differentiated them into cells of mesenchymal lineages (bone, cartilage, and fat) in vitro, and in three-dimensional fabricated polycaprolactone and polycaprolactone–tricalcium phosphate scaffolds. Taken together, our data showed the existence of rabbit palatum-derived mesenchymal progenitor cells, and successful fabrication of progenitor cell-loaded biodegradable scaffold using three-dimensional printing. This study will open avenues for new tissue engineering strategies for cell therapy using three-dimensional printing with scaffolds for reconstruction of head and neck defects.

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Kim, Gyeong-Ji, Kwon-Jai Lee, Jeong-Woo Choi, and Jeung Hee An. "Modified Industrial Three-Dimensional Polylactic Acid Scaffold Cell Chip Promotes the Proliferation and Differentiation of Human Neural Stem Cells." International Journal of Molecular Sciences 23, no. 4 (February 17, 2022): 2204. http://dx.doi.org/10.3390/ijms23042204.

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In this study, we fabricated a three-dimensional (3D) scaffold using industrial polylactic acid (PLA), which promoted the proliferation and differentiation of human neural stem cells. An industrial PLA 3D scaffold (IPTS) cell chip with a square-shaped pattern was fabricated via computer-aided design and printed using a fused deposition modeling technique. To improve cell adhesion and cell differentiation, we coated the IPTS cell chip with gold nanoparticles (Au-NPs), nerve growth factor (NGF) protein, an NGF peptide fragment, and sonic hedgehog (SHH) protein. The proliferation of F3.Olig2 neural stem cells was increased in the IPTS cell chips coated with Au-NPs and NGF peptide fragments when compared with that of the cells cultured on non-coated IPTS cell chips. Cells cultured on the IPTS-SHH cell chip also showed high expression of motor neuron cell-specific markers, such as HB9 and TUJ-1. Therefore, we suggest that the newly engineered industrial PLA scaffold is an innovative tool for cell proliferation and motor neuron differentiation.

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Chooi, Wai Hon, William Ong, Aoife Murray, Junquan Lin, Dean Nizetic, and Sing Yian Chew. "Scaffold mediated gene knockdown for neuronal differentiation of human neural progenitor cells." Biomaterials Science 6, no. 11 (2018): 3019–29. http://dx.doi.org/10.1039/c8bm01034j.

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Qin, Jingwen, Meizhi Wang, Tianyun Zhao, Xue Xiao, Xuejun Li, Jieping Yang, Lisha Yi, Andre M. Goffinet, Yibo Qu, and Libing Zhou. "Early Forebrain Neurons and Scaffold Fibers in Human Embryos." Cerebral Cortex 30, no. 3 (July 11, 2019): 913–28. http://dx.doi.org/10.1093/cercor/bhz136.

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Abstract Neural progenitor proliferation, neuronal migration, areal organization, and pioneer axon wiring are critical events during early forebrain development, yet remain incompletely understood, especially in human. Here, we studied forebrain development in human embryos aged 5 to 8 postconceptional weeks (WPC5–8), stages that correspond to the neuroepithelium/early marginal zone (WPC5), telencephalic preplate (WPC6 & 7), and incipient cortical plate (WPC8). We show that early telencephalic neurons are formed at the neuroepithelial stage; the most precocious ones originate from local telencephalic neuroepithelium and possibly from the olfactory placode. At the preplate stage, forebrain organization is quite similar in human and mouse in terms of areal organization and of differentiation of Cajal-Retzius cells, pioneer neurons, and axons. Like in mice, axons from pioneer neurons in prethalamus, ventral telencephalon, and cortical preplate cross the diencephalon–telencephalon junction and the pallial–subpallial boundary, forming scaffolds that could guide thalamic and cortical axons at later stages. In accord with this model, at the early cortical plate stage, corticofugal axons run in ventral telencephalon in close contact with scaffold neurons, which express CELSR3 and FZD3, two molecules that regulates formation of similar scaffolds in mice.

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Journal articles on the topic 'Neural scaffold'

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