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1

Russell, Lauren N., and Kyle J. Lampe. "Engineering Biomaterials to Influence Oligodendroglial Growth, Maturation, and Myelin Production." Cells Tissues Organs 202, no. 1-2 (2016): 85–101. http://dx.doi.org/10.1159/000446645.

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Millions of people suffer from damage or disease to the nervous system that results in a loss of myelin, such as through a spinal cord injury or multiple sclerosis. Diminished myelin levels lead to further cell death in which unmyelinated neurons die. In the central nervous system, a loss of myelin is especially detrimental because of its poor ability to regenerate. Cell therapies such as stem or precursor cell injection have been investigated as stem cells are able to grow and differentiate into the damaged cells; however, stem cell injection alone has been unsuccessful in many areas of neural regeneration. Therefore, researchers have begun exploring combined therapies with biomaterials that promote cell growth and differentiation while localizing cells in the injured area. The regrowth of myelinating oligodendrocytes from neural stem cells through a biomaterials approach may prove to be a beneficial strategy following the onset of demyelination. This article reviews recent advancements in biomaterial strategies for the differentiation of neural stem cells into oligodendrocytes, and presents new data indicating appropriate properties for oligodendrocyte precursor cell growth. In some cases, an increase in oligodendrocyte differentiation alongside neurons is further highlighted for functional improvements where the biomaterial was then tested for increased myelination both in vitro and in vivo.
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Little, Lauren, Kevin E. Healy, and David Schaffer. "Engineering Biomaterials for Synthetic Neural Stem Cell Microenvironments." Chemical Reviews 108, no. 5 (May 2008): 1787–96. http://dx.doi.org/10.1021/cr078228t.

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3

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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4

Xia, Lin, Wenjuan Zhu, Yunfeng Wang, Shuangba He, and Renjie Chai. "Regulation of Neural Stem Cell Proliferation and Differentiation by Graphene-Based Biomaterials." Neural Plasticity 2019 (October 16, 2019): 1–11. http://dx.doi.org/10.1155/2019/3608386.

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The transplantation of neural stem cells (NSCs) has become an emerging treatment for neural degeneration. A key factor in such treatments is to manipulate NSC behaviors such as proliferation and differentiation, resulting in the eventual regulation of NSC fate. Novel bionanomaterials have shown usefulness in guiding the proliferation and differentiation of NSCs due to the materials’ unique morphological and topological properties. Among the nanomaterials, graphene has drawn increasing attention for neural regeneration applications based on the material’s excellent physicochemical properties, surface modifications, and biocompatibility. In this review, we summarize recent works on the use of graphene-based biomaterials for regulating NSC behaviors and the potential use of these materials in clinical treatment. We also discuss the limitations of graphene-based nanomaterials for use in clinical practice. Finally, we provide some future prospects for graphene-based biomaterial applications in neural regeneration.
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5

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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6

Assunção-Silva, Rita C., Eduardo D. Gomes, Nuno Sousa, Nuno A. Silva, and António J. Salgado. "Hydrogels and Cell Based Therapies in Spinal Cord Injury Regeneration." Stem Cells International 2015 (2015): 1–24. http://dx.doi.org/10.1155/2015/948040.

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Spinal cord injury (SCI) is a central nervous system- (CNS-) related disorder for which there is yet no successful treatment. Within the past several years, cell-based therapies have been explored for SCI repair, including the use of pluripotent human stem cells, and a number of adult-derived stem and mature cells such as mesenchymal stem cells, olfactory ensheathing cells, and Schwann cells. Although promising, cell transplantation is often overturned by the poor cell survival in the treatment of spinal cord injuries. Alternatively, the therapeutic role of different cells has been used in tissue engineering approaches by engrafting cells with biomaterials. The latter have the advantages of physically mimicking the CNS tissue, while promoting a more permissive environment for cell survival, growth, and differentiation. The roles of both cell- and biomaterial-based therapies as single therapeutic approaches for SCI repair will be discussed in this review. Moreover, as the multifactorial inhibitory environment of a SCI suggests that combinatorial approaches would be more effective, the importance of using biomaterials as cell carriers will be herein highlighted, as well as the recent advances and achievements of these promising tools for neural tissue regeneration.
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7

Kang, Phillip H., Sanjay Kumar, and David V. Schaffer. "Novel biomaterials to study neural stem cell mechanobiology and improve cell-replacement therapies." Current Opinion in Biomedical Engineering 4 (December 2017): 13–20. http://dx.doi.org/10.1016/j.cobme.2017.09.005.

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8

Dai, Xizi, and Yen-Chih Huang. "Pluripotent Stem Cell Derived Neural Lineage Cells and Biomaterials for Neuroscience and Neuroengineering." Journal of Neuroscience and Neuroengineering 2, no. 2 (April 1, 2013): 119–40. http://dx.doi.org/10.1166/jnsne.2013.1047.

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9

Soria, Jose Miguel, María Sancho-Tello, M. Angeles Garcia Esparza, Vicente Mirabet, Jose Vicente Bagan, Manuel Monleón, and Carmen Carda. "Biomaterials coated by dental pulp cells as substrate for neural stem cell differentiation." Journal of Biomedical Materials Research Part A 97A, no. 1 (February 11, 2011): 85–92. http://dx.doi.org/10.1002/jbm.a.33032.

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10

Maclean, Francesca L., Alexandra L. Rodriguez, Clare L. Parish, Richard J. Williams, and David R. Nisbet. "Integrating Biomaterials and Stem Cells for Neural Regeneration." Stem Cells and Development 25, no. 3 (February 2016): 214–26. http://dx.doi.org/10.1089/scd.2015.0314.

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11

Yang, Letao, Brian M. Conley, Jinho Yoon, Christopher Rathnam, Thanapat Pongkulapa, Brandon Conklin, Yannan Hou, and Ki-Bum Lee. "High-Content Screening and Analysis of Stem Cell-Derived Neural Interfaces Using a Combinatorial Nanotechnology and Machine Learning Approach." Research 2022 (September 15, 2022): 1–15. http://dx.doi.org/10.34133/2022/9784273.

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A systematic investigation of stem cell-derived neural interfaces can facilitate the discovery of the molecular mechanisms behind cell behavior in neurological disorders and accelerate the development of stem cell-based therapies. Nevertheless, high-throughput investigation of the cell-type-specific biophysical cues associated with stem cell-derived neural interfaces continues to be a significant obstacle to overcome. To this end, we developed a combinatorial nanoarray-based method for high-throughput investigation of neural interface micro-/nanostructures (physical cues comprising geometrical, topographical, and mechanical aspects) and the effects of these complex physical cues on stem cell fate decisions. Furthermore, by applying a machine learning (ML)-based analytical approach to a large number of stem cell-derived neural interfaces, we comprehensively mapped stem cell adhesion, differentiation, and proliferation, which allowed for the cell-type-specific design of biomaterials for neural interfacing, including both adult and human-induced pluripotent stem cells (hiPSCs) with varying genetic backgrounds. In short, we successfully demonstrated how an innovative combinatorial nanoarray and ML-based platform technology can aid with the rational design of stem cell-derived neural interfaces, potentially facilitating precision, and personalized tissue engineering applications.
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12

Zhong, Yinghui, and Ravi V. Bellamkonda. "Biomaterials for the central nervous system." Journal of The Royal Society Interface 5, no. 26 (May 13, 2008): 957–75. http://dx.doi.org/10.1098/rsif.2008.0071.

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Biomaterials are widely used to help treat neurological disorders and/or improve functional recovery in the central nervous system (CNS). This article reviews the application of biomaterials in (i) shunting systems for hydrocephalus, (ii) cortical neural prosthetics, (iii) drug delivery in the CNS, (iv) hydrogel scaffolds for CNS repair, and (v) neural stem cell encapsulation for neurotrauma. The biological and material requirements for the biomaterials in these applications are discussed. The difficulties that the biomaterials might face in each application and the possible solutions are also reviewed in this article.
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13

Barros, Daniela, Isabel F. Amaral, and Ana P. Pêgo. "Laminin-Inspired Cell-Instructive Microenvironments for Neural Stem Cells." Biomacromolecules 21, no. 2 (December 2, 2019): 276–93. http://dx.doi.org/10.1021/acs.biomac.9b01319.

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14

Bruggeman, K. F., N. Moriarty, E. Dowd, D. R. Nisbet, and C. L. Parish. "Harnessing stem cells and biomaterials to promote neural repair." British Journal of Pharmacology 176, no. 3 (December 21, 2018): 355–68. http://dx.doi.org/10.1111/bph.14545.

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15

Kurakula, Mallesh, Shashank Gorityala, Devang B. Patel, Pratap Basim, Bhaumik Patel, and Saurabh Kumar Jha. "Trends of Chitosan Based Delivery Systems in Neuroregeneration and Functional Recovery in Spinal Cord Injuries." Polysaccharides 2, no. 2 (June 15, 2021): 519–37. http://dx.doi.org/10.3390/polysaccharides2020031.

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Spinal cord injury (SCI) is one of the most complicated nervous system injuries with challenging treatment and recovery. Regenerative biomaterials such as chitosan are being reported for their wide use in filling the cavities, deliver curative drugs, and also provide adsorption sites for transplanted stem cells. Biomaterial scaffolds utilizing chitosan have shown certain therapeutic effects on spinal cord injury repair with some limitations. Chitosan-based delivery in stem cell transplantation is another strategy that has shown decent success. Stem cells can be directed to differentiate into neurons or glia in vitro. Stem cell-based therapy, biopolymer chitosan delivery strategies, and scaffold-based therapeutic strategies have been advancing as a combinatorial approach for spinal cord injury repair. In this review, we summarize the recent progress in the treatment strategies of SCI due to the use of bioactivity of chitosan-based drug delivery systems. An emphasis on the role of chitosan in neural regeneration has also been highlighted.
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16

Cui, Fu-Zhai, Hua Deng, Ci-Feng Fang, Yue-Teng Wei, and Xing-Can Shen. "A Mini Review on Interactions Between Neural Stem Cells and Biomaterials." Recent Patents on Regenerative Medicine 1, no. 1 (March 21, 2011): 19–29. http://dx.doi.org/10.2174/2210297311101010019.

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17

Li, Yi-Chen, Li-Kai Tsai, Jyh-Horng Wang, and Tai-Horng Young. "A neural stem/precursor cell monolayer for neural tissue engineering." Biomaterials 35, no. 4 (January 2014): 1192–204. http://dx.doi.org/10.1016/j.biomaterials.2013.10.066.

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18

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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19

Han, Hao-Wei, Ling-Ning Ko, Chii-Shen Yang, and Shan-hui Hsu. "Potential of Engineered Bacteriorhodopsins as Photoactivated Biomaterials in Modulating Neural Stem Cell Behavior." ACS Biomaterials Science & Engineering 5, no. 6 (May 22, 2019): 3068–78. http://dx.doi.org/10.1021/acsbiomaterials.9b00367.

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20

Little, Lauren E., Karen Y. Dane, Patrick S. Daugherty, Kevin E. Healy, and David V. Schaffer. "Exploiting bacterial peptide display technology to engineer biomaterials for neural stem cell culture." Biomaterials 32, no. 6 (February 2011): 1484–94. http://dx.doi.org/10.1016/j.biomaterials.2010.10.032.

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21

Xue, Weiwei, Caixia Fan, Bing Chen, Yannan Zhao, Zhifeng Xiao, and Jianwu Dai. "Direct Neuronal Differentiation of Neural Stem Cells for Spinal Cord Injury Repair." Stem Cells 39, no. 8 (March 5, 2021): 1025–32. http://dx.doi.org/10.1002/stem.3366.

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Abstract Spinal cord injury (SCI) typically results in long-lasting functional deficits, largely due to primary and secondary wh ite matter damage at the site of injury. The transplantation of neural stem cells (NSCs) has shown promise for re-establishing communications between separated regions of the spinal cord through the insertion of new neurons between the injured axons and target neurons. However, the inhibitory microenvironment that develops after SCI often causes endogenous and transplanted NSCs to differentiate into glial cells rather than neurons. Functional biomaterials have been shown to mitigate the effects of the adverse SCI microenvironment and promote the neuronal differentiation of NSCs. A clear understanding of the mechanisms of neuronal differentiation within the injury-induced microenvironment would likely allow for the development of treatment strategies designed to promote the innate ability of NSCs to differentiate into neurons. The increased differentiation of neurons may contribute to relay formation, facilitating functional recovery after SCI. In this review, we summarize current strategies used to enhance the neuronal differentiation of NSCs through the reconstruction of the SCI microenvironment and to improve the intrinsic neuronal differentiation abilities of NSCs, which is significant for SCI repair.
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22

Wang, Ying, Hua Deng, Zhao-Hui Zu, Xing-Can Shen, Hong Liang, Fu-Zhai Cui, Qun-Yuan Xu, and In-Seop Lee. "Interactions between neural stem cells and biomaterials combined with biomolecules." Frontiers of Materials Science in China 4, no. 4 (November 12, 2010): 325–31. http://dx.doi.org/10.1007/s11706-010-0113-1.

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23

Zimmermann, Joshua A., and David V. Schaffer. "Engineering biomaterials to control the neural differentiation of stem cells." Brain Research Bulletin 150 (August 2019): 50–60. http://dx.doi.org/10.1016/j.brainresbull.2019.05.007.

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24

Li, Mo, Ying Wang, Jidi Zhang, Zheng Cao, Shuo Wang, Wei Zheng, Qian Li, et al. "Culture of pyramidal neural precursors, neural stem cells, and fibroblasts on various biomaterials." Journal of Biomaterials Science, Polymer Edition 29, no. 17 (November 22, 2018): 2168–86. http://dx.doi.org/10.1080/09205063.2018.1528520.

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25

Nakajima, Masafumi, Toshinari Ishimuro, Koichi Kato, In-Kap Ko, Isao Hirata, Yusuke Arima, and Hiroo Iwata. "Combinatorial protein display for the cell-based screening of biomaterials that direct neural stem cell differentiation." Biomaterials 28, no. 6 (February 2007): 1048–60. http://dx.doi.org/10.1016/j.biomaterials.2006.10.004.

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26

Solanki, Aniruddh, Shreyas Shah, Kevin A. Memoli, Sung Young Park, Seunghun Hong, and Ki-Bum Lee. "Stem cell differentiation: Controlling Differentiation of Neural Stem Cells Using Extracellular Matrix Protein Patterns (Small 22/2010)." Small 6, no. 22 (November 22, 2010): 2508. http://dx.doi.org/10.1002/smll.201090079.

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27

Di Tinco, Rosanna, Ugo Consolo, Alessandra Pisciotta, Giulia Orlandi, Giulia Bertani, Milena Nasi, Jessika Bertacchini, and Gianluca Carnevale. "Characterization of Dental Pulp Stem Cells Response to Bone Substitutes Biomaterials in Dentistry." Polymers 14, no. 11 (May 30, 2022): 2223. http://dx.doi.org/10.3390/polym14112223.

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Bone substitute biomaterials (BSBs) represent a promising alternative to bone autografts, due to their biocompatibility, osteoconduction, slow resorption rates, and the ability to define and maintain volume for bone gain in dentistry. Many biomaterials are tailored to provide structural and biological support for bone regeneration, and allow the migration of bone-forming cells into the bone defect. Neural crest-derived stem cells isolated from human dental pulp (hDPSCs) represent a suitable stem cell source to study the biological effects of BSBs on osteoprogenitor cells involved in the physiological bone regenerative processes. This study aimed to evaluate how three different BSBs affect the stem cell properties, osteogenic differentiation, and inflammatory properties of hDPSCs. Our data highlight that BSBs do not alter cell proliferation and stemness markers expression, nor induce any inflammatory responses. Bone metabolism data show that hDPSCs exposed to the three BSBs distinctively secrete the factors supporting osteoblast activity and osteoclast activity. Our data indicate that (i) hDPSCs are a suitable stem cell source to study the effects of BSBs, and that (ii) the formulation of BSBs may condition the biological properties of stem cells, suggesting their versatile suitability to different dentistry applications.
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28

Scanga, Vanessa I., Alex Goraltchouk, Nasser Nussaiba, Molly S. Shoichet, and Cindi M. Morshead. "Biomaterials for neural-tissue engineering — Chitosan supports the survival, migration, and differentiation of adult-derived neural stem and progenitor cells." Canadian Journal of Chemistry 88, no. 3 (March 2010): 277–87. http://dx.doi.org/10.1139/v09-171.

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Neural precursor cells (NPCs or stem and progenitor cells) are promising in transplantation strategies to treat an injury to the central nervous system, such as a spinal cord injury (SCI), because of their ability to differentiate into neurons and glia. Transplantation studies to date have met with limited success for a number of reasons, including poor cell survival. One way to encourage cell survival in injured tissue is to provide the cells with a scaffold to enhance their survival, their integration, and potentially their differentiation into appropriate cell types. Towards this end, four amine-functionalized hydrogels were screened in vitro for adult murine NPC viability, migration, and differentiation: chitosan, poly(oligoethylene oxide dimethacrylate-co-2-amino ethyl methacrylate), blends of poly(oligoethylene oxide dimethacrylate-co-2-amino ethyl methacrylate), and poly(vinyl alcohol), and poly(glycerol dimethacrylate-co-2-amino ethyl methacrylate). The greatest cell viability was found on chitosan at all times examined, Chitosan had the greatest surface amine content and the lowest equilibrium water content, which likely contributed to the greater NPC viability observed over three weeks in culture. Only chitosan supported survival of multipotent stem cells and the differentiation of the progenitors into neurons, astrocytes, and oligodendrocytes. Plating intact NPC colonies revealed greater cell migration on chitosan relative to the other hydrogels. Importantly, long term cultures on chitosan showed no significant difference in total cell counts over time, suggesting no net cell growth. Together, these findings reveal chitosan as a promising material for the delivery of adult NPC cell-based therapies.
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29

Petersen, Latrisha K., Jisun Oh, Donald S. Sakaguchi, Surya K. Mallapragada, and Balaji Narasimhan. "Amphiphilic Polyanhydride Films Promote Neural Stem Cell Adhesion and Differentiation." Tissue Engineering Part A 17, no. 19-20 (October 2011): 2533–41. http://dx.doi.org/10.1089/ten.tea.2011.0095.

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Cui, Fu-Zhai, Hua Deng, Ci-Feng Fang, Yue-Teng Wei, and Xing-Can Shen. "A Mini Review on Interactions Between Neural Stem Cells and Biomaterials." Recent Patents on Regenerative Medicinee 1, no. 1 (January 1, 2011): 19–29. http://dx.doi.org/10.2174/2210296511101010019.

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Li, Cui, Mitchell Kuss, Yunfan Kong, Fujiao Nie, Xiaoyan Liu, Bo Liu, Anna Dunaevsky, Pierre Fayad, Bin Duan, and Xiaowei Li. "3D Printed Hydrogels with Aligned Microchannels to Guide Neural Stem Cell Migration." ACS Biomaterials Science & Engineering 7, no. 2 (January 28, 2021): 690–700. http://dx.doi.org/10.1021/acsbiomaterials.0c01619.

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32

Khaing, Zin Z., and Stephanie K. Seidlits. "Hyaluronic acid and neural stem cells: implications for biomaterial design." J. Mater. Chem. B 3, no. 40 (2015): 7850–66. http://dx.doi.org/10.1039/c5tb00974j.

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While in the past hyaluronic acid (HA) was considered a passive structural component, research over the past few decades has revealed its diverse and complex biological functions resulting in a major ideological shift. This review describes recent advances in biological interactions of HA with neural stem cells, with a focus on leveraging these interactions to develop advanced biomaterials that aid regeneration of the central nervous system.
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Zhai, Yuanxin, Quanwei Wang, Zhanchi Zhu, Wenlong Zheng, Sancheng Ma, Ying Hao, Lingyan Yang, and Guosheng Cheng. "Cell-derived extracellular matrix enhanced by collagen-binding domain-decorated exosomes to promote neural stem cells neurogenesis." Biomedical Materials 17, no. 1 (December 20, 2021): 014104. http://dx.doi.org/10.1088/1748-605x/ac4089.

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Abstract Enhancing neurogenesis of neural stem cells (NSCs) is crucial in stem cell therapy for neurodegenerative diseases. Within the extracellular microenvironment, extracellular matrix (ECM) plays a pivotal role in modulating cell behaviors. However, a single ECM biomaterial is not sufficient to establish an ideal microenvironment. As multifunctional nanocarriers, exosomes display tremendous advantages for the treatments of various diseases. Herein, collagen binding domain peptide-modified exosomes (CBD-Exo) were obtained from the SH-SY5Y cell line infected with lentivirus particles encoding CBD-lysosome associated membrane glycoprotein 2b (CBD-Lamp2b) to improve the binding efficiency of exosomes and ECM. An exosomes-functionalized ECM (CBD-Exo/ECM) was then constructed via the interaction between CBD and collagen in ECM. Then, CBD-Exo/ECM was employed as a carrier for NSCs culture. The results showed that CBD-Exo/ECM can support the neurogenesis of NSCs with the percentage of proliferation marker EdU-positive (35.8% ± 0.47% vs 21.9% ± 2.32%) and neuron maker Tuj-1-positive (55.8% ± 0.47% vs 30.6% ± 2.62%) were both significantly increased in the exosomes-functionalized ECM system. This exosomes-functionalized ECM was capable to promote the cell proliferation and accelerate neuronal differentiation of NSCs, providing a potential biomedical material for stem cell application in tissue engineering and regenerative medicine.
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Pandanaboina, Sahitya Chetan, Ambar B. RanguMagar, Krishna D. Sharma, Bijay P. Chhetri, Charlette M. Parnell, Jennifer Yanhua Xie, Malathi Srivatsan, and Anindya Ghosh. "Functionalized Nanocellulose Drives Neural Stem Cells toward Neuronal Differentiation." Journal of Functional Biomaterials 12, no. 4 (November 22, 2021): 64. http://dx.doi.org/10.3390/jfb12040064.

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Transplantation of differentiated and fully functional neurons may be a better therapeutic option for the cure of neurodegenerative disorders and brain injuries than direct grafting of neural stem cells (NSCs) that are potentially tumorigenic. However, the differentiation of NSCs into a large population of neurons has been a challenge. Nanomaterials have been widely used as substrates to manipulate cell behavior due to their nano-size, excellent physicochemical properties, ease of synthesis, and versatility in surface functionalization. Nanomaterial-based scaffolds and synthetic polymers have been fabricated with topology resembling the micro-environment of the extracellular matrix. Nanocellulose materials are gaining attention because of their availability, biocompatibility, biodegradability and bioactivity, and affordable cost. We evaluated the role of nanocellulose with different linkage and surface features in promoting neuronal differentiation. Nanocellulose coupled with lysine molecules (CNC–Lys) provided positive charges that helped the cells to attach. Embryonic rat NSCs were differentiated on the CNC–Lys surface for up to three weeks. By the end of the three weeks of in vitro culture, 87% of the cells had attached to the CNC–Lys surface and more than half of the NSCs had differentiated into functional neurons, expressing endogenous glutamate, generating electrical activity and action potentials recorded by the multi-electrode array.
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35

Qu, Jing, and Huanxiang Zhang. "Roles of Mesenchymal Stem Cells in Spinal Cord Injury." Stem Cells International 2017 (2017): 1–12. http://dx.doi.org/10.1155/2017/5251313.

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Spinal cord injury (SCI) represents one of the most complicated and heterogeneous pathological processes of central nervous system (CNS) impairments, which is still beyond functional regeneration. Transplantation of mesenchymal stem cells (MSCs) has been shown to promote the repair of the injured spinal cord tissues in animal models, and therefore, there is much interest in the clinical use of these cells. However, many questions which are essential to improve the therapy effects remain unanswered. For instance, the functional roles and related molecular regulatory mechanisms of MSCs in vivo are not yet completely determined. It is important for transplanted cells to migrate into the injured tissue, to survive and undergo neural differentiation, or to play neural protection roles by various mechanisms after SCI. In this review, we will focus on some of the recent knowledge about the biological behavior and function of MSCs in SCI. Meanwhile, we highlight the function of biomaterials to direct the behavior of MSCs based on our series of work on silk fibroin biomaterials and attempt to emphasize combinational strategies such as tissue engineering for functional improvement of SCI.
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Muhammad Usman Khalid and Taleaa Masroor. "The promise of stem cells in amyotrophic lateral sclerosis: a review of clinical trials." Journal of the Pakistan Medical Association 73, no. 2 (January 25, 2023): S138—S142. http://dx.doi.org/10.47391/jpma.akus-22.

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Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative condition with high cost of care, poor treatment outcomes, and a significant decrease in quality of life, eventually culminating in high mortality rates. Stem cells present an attractive alternative to conventional therapies as they can regenerate tissue and introduce growth factors to slow down the progression of disease. We conducted a comprehensive review of literature available in the MEDLINE (PUBMED), Scopus, and Cochrane Library databases, of current usage of stem cells and stem cell-based biomaterials for ALS treatment. Clinical trials, less than 10 years old, on human subjects were included in the study. Overall, stem cells, whether mesenchymal, non-lineage, or neural stem cells all seem safe for use in therapy for ALS. However, due to the chronic nature of the disease the efficacy of the treatment is not proven and warrants further investigation. Keywords: Amyotrophic Lateral Sclerosis. Biocompatible Materials, Neural, Stem Cells
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Yin, Zhaoyang, Jian Yin, Yongfeng Huo, Guangxue Gu, Jian Yu, Aimin Li, and Jinhai Tang. "KCC2 overexpressed exosomes meditated spinal cord injury recovery in mice." Biomedical Materials 17, no. 6 (October 20, 2022): 064104. http://dx.doi.org/10.1088/1748-605x/ac956b.

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Abstract Exosomes show great potential in treating diseases of the central nervous system including spinal cord injury (SCI), still better engineered exosomes have more advantages. In this study, we purified exosomes from K+–Cl− co-transporter (KCC2) overexpressed bone marrow mesenchymal stem cells (ExoKCC2), to investigate the effect of ExoKCC2 on neural differentiation in vitro and the repairing function of ExoKCC2 in SCI mice in vivo. Compared to bone marrow mesenchymal stem cells (BMSC)-derived exosomes (Exo), ExoKCC2 could better promote neural stem cell differentiated into neurons, ameliorate the function recovery of SCI mice, and accelerate the neural regeneration at the lesion site. Altogether, engineered ExoKCC2 may prove to be an advantageous strategy for SCI treatment.
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Thonhoff, Jason R., Dianne I. Lou, Paivi M. Jordan, Xu Zhao, and Ping Wu. "Compatibility of human fetal neural stem cells with hydrogel biomaterials in vitro." Brain Research 1187 (January 2008): 42–51. http://dx.doi.org/10.1016/j.brainres.2007.10.046.

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Fantini, Valentina, Matteo Bordoni, Franca Scocozza, Michele Conti, Eveljn Scarian, Stephana Carelli, Anna Maria Di Giulio, et al. "Bioink Composition and Printing Parameters for 3D Modeling Neural Tissue." Cells 8, no. 8 (August 5, 2019): 830. http://dx.doi.org/10.3390/cells8080830.

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Neurodegenerative diseases (NDs) are a broad class of pathologies characterized by the progressive loss of neurons in the central nervous system. The main problem in the study of NDs is the lack of an adequate realistic experimental model to study the pathogenic mechanisms. Induced pluripotent stem cells (iPSCs) partially overcome the problem, with their capability to differentiate into almost every cell types; even so, these cells alone are not sufficient to unveil the mechanisms underlying NDs. 3D bioprinting allows to control the distribution of cells such as neurons, leading to the creation of a realistic in vitro model. In this work, we analyzed two biomaterials: sodium alginate and gelatin, and three different cell types: a neuroblastoma cell line (SH-SY5Y), iPSCs, and neural stem cells. All cells were encapsulated inside the bioink, printed and cultivated for at least seven days; they all presented good viability. We also evaluated the maintenance of the printed shape, opening the possibility to obtain a reliable in vitro neural tissue combining 3D bioprinting and iPSCs technology, optimizing the study of the degenerative processes that are still widely unknown.
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Saha, Krishanu, Elizabeth F. Irwin, Julia Kozhukh, David V. Schaffer, and Kevin E. Healy. "Biomimetic interfacial interpenetrating polymer networks control neural stem cell behavior." Journal of Biomedical Materials Research Part A 81A, no. 1 (April 2007): 240–49. http://dx.doi.org/10.1002/jbm.a.30986.

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41

Laundos, Tiago L., Joana Silva, Marisa Assunção, Pedro Quelhas, Cátia Monteiro, Carla Oliveira, Maria J. Oliveira, Ana P. Pêgo, and Isabel F. Amaral. "Rotary orbital suspension culture of embryonic stem cell-derived neural stem/progenitor cells: impact of hydrodynamic culture on aggregate yield, morphology and cell phenotype." Journal of Tissue Engineering and Regenerative Medicine 11, no. 8 (February 15, 2016): 2227–40. http://dx.doi.org/10.1002/term.2121.

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Wilems, Thomas, Sangamithra Vardhan, Siliang Wu, and Shelly Sakiyama-Elbert. "The influence of microenvironment and extracellular matrix molecules in driving neural stem cell fate within biomaterials." Brain Research Bulletin 148 (May 2019): 25–33. http://dx.doi.org/10.1016/j.brainresbull.2019.03.004.

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43

Wang, Ying, Zhen Xu, Lance C. Kam, and Peng Shi. "Site-Specific Differentiation of Neural Stem Cell Regulated by Micropatterned Multicomponent Interfaces." Advanced Healthcare Materials 3, no. 2 (June 25, 2013): 214–20. http://dx.doi.org/10.1002/adhm.201300082.

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44

Fuhrer, Erwin, Anne Bäcker, Stephanie Kraft, Friederike J. Gruhl, Matthias Kirsch, Neil MacKinnon, Jan G. Korvink, and Swati Sharma. "3D Carbon Scaffolds for Neural Stem Cell Culture and Magnetic Resonance Imaging." Advanced Healthcare Materials 7, no. 4 (December 21, 2017): 1700915. http://dx.doi.org/10.1002/adhm.201700915.

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45

Wei, Yali, Ping Lyu, Ruiye Bi, Xinyu Chen, Yanshen Yu, Zucen Li, and Yi Fan. "Neural Regeneration in Regenerative Endodontic Treatment: An Overview and Current Trends." International Journal of Molecular Sciences 23, no. 24 (December 7, 2022): 15492. http://dx.doi.org/10.3390/ijms232415492.

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Pulpal and periapical diseases are the most common dental diseases. The traditional treatment is root canal therapy, which achieves satisfactory therapeutic outcomes—especially for mature permanent teeth. Apexification, pulpotomy, and pulp revascularization are common techniques used for immature permanent teeth to accelerate the development of the root. However, there are obstacles to achieving functional pulp regeneration. Recently, two methods have been proposed based on tissue engineering: stem cell transplantation, and cell homing. One of the goals of functional pulp regeneration is to achieve innervation. Nerves play a vital role in dentin formation, nutrition, sensation, and defense in the pulp. Successful neural regeneration faces tough challenges in both animal studies and clinical trials. Investigation of the regeneration and repair of the nerves in the pulp has become a serious undertaking. In this review, we summarize the current understanding of the key stem cells, signaling molecules, and biomaterials that could promote neural regeneration as part of pulp regeneration. We also discuss the challenges in preclinical or clinical neural regeneration applications to guide deep research in the future.
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Li, Hang, Jukuan Zheng, Huifeng Wang, Mathew L. Becker, and Nic D. Leipzig. "Neural stem cell encapsulation and differentiation in strain promoted crosslinked polyethylene glycol-based hydrogels." Journal of Biomaterials Applications 32, no. 9 (February 2, 2018): 1222–30. http://dx.doi.org/10.1177/0885328218755711.

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47

Spagnuolo, Gianrico, Bruna Codispoti, Massimo Marrelli, Carlo Rengo, Sandro Rengo, and Marco Tatullo. "Commitment of Oral-Derived Stem Cells in Dental and Maxillofacial Applications." Dentistry Journal 6, no. 4 (December 13, 2018): 72. http://dx.doi.org/10.3390/dj6040072.

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Tissue engineering is based on the interaction between stem cells, biomaterials and factors delivered in biological niches. Oral tissues have been found to be rich in stem cells from different sources: Stem cells from oral cavity are easily harvestable and have shown a great plasticity towards the main lineages, specifically towards bone tissues. Dental pulp stem cells (DPSCs) are the most investigated mesenchymal stem cells (MSCs) from dental tissues, however, the oral cavity hosts several other stem cell lineages that have also been reported to be a good alternative in bone tissue engineering. In particular, the newly discovered population of mesenchymal stem cells derived from human periapical inflamed cysts (hPCy-MSCs) have showed very promising properties, including high plasticity toward bone, vascular and neural phenotypes. In this topical review, the authors described the main oral-derived stem cell populations, their most interesting characteristics and their ability towards osteogenic lineage. This review has also investigated the main clinical procedures, reported in the recent literature, involving oral derived-MSCs and biomaterials to get better bone regeneration in dental procedures. The numerous populations of mesenchymal stem cells isolated from oral tissues (DPSCs, SHEDs, PDLSCs, DFSCs, SCAPs, hPCy-MSCs) retain proliferation ability and multipotency; these features are exploited for clinical purposes, including regeneration of injured tissues and local immunomodulation; we reported on the last studies on the proper use of such MSCs within a biological niche and the proper way to storage them for future clinical use.
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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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Cao, Yuheng, Haobo He, Kaili Cao, Yongyang Liu, Dehua Huang, Tuanwei Li, and Guangcun Chen. "Linear-branched poly(β-amino esters)/DNA nano-polyplexes for effective gene transfection and neural stem cell differentiation." Biomedical Materials 17, no. 2 (February 7, 2022): 024105. http://dx.doi.org/10.1088/1748-605x/ac4e64.

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Abstract Controllable regulation of stem cell differentiation is a critical concern in stem cell-based regenerative medicine. In particular, there are still great challenges in controlling the directional differentiation of neural stem cells (NSCs) into neurons. Herein, we developed a novel linear-branched poly(β-amino esters) (S4-TMPTA-BDA-DT, STBD) through a two-step reaction. The synthesized linear-branched polymers possess multiple positively charged amine terminus and degradable intermolecular ester bonds, thus endowing them with excellent properties such as high gene load, efficient gene delivery, and effective gene release and transcription in cells. In the mCherry transfection test, a high transfection efficiency of approximately 70% was achieved in primary NSCs after a single transfection. Moreover, STBD also showed high biocompatibility to NSCs without disturbing their viability and neural differentiation. With the high gene delivery property, STBD is capable of delivering siRNA (shSOX9) expression plasmid into NSCs to significantly interfere with the expression of SOX9, thus enhancing the neuronal differentiation and maturation of NSCs. The STBD/DNA nano-polyplex represents a powerful non-viral approach of gene delivery for manipulating the differentiation of stem cells, showing broad application prospects in NSC-based regenerative therapy for treating neurodegenerative diseases.
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Ratajczak, Jessica, Annelies Bronckaers, Yörg Dillen, Pascal Gervois, Tim Vangansewinkel, Ronald B. Driesen, Esther Wolfs, Ivo Lambrichts, and Petra Hilkens. "The Neurovascular Properties of Dental Stem Cells and Their Importance in Dental Tissue Engineering." Stem Cells International 2016 (2016): 1–17. http://dx.doi.org/10.1155/2016/9762871.

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Within the field of tissue engineering, natural tissues are reconstructed by combining growth factors, stem cells, and different biomaterials to serve as a scaffold for novel tissue growth. As adequate vascularization and innervation are essential components for the viability of regenerated tissues, there is a high need for easily accessible stem cells that are capable of supporting these functions. Within the human tooth and its surrounding tissues, different stem cell populations can be distinguished, such as dental pulp stem cells, stem cells from human deciduous teeth, stem cells from the apical papilla, dental follicle stem cells, and periodontal ligament stem cells. Given their straightforward and relatively easy isolation from extracted third molars, dental stem cells (DSCs) have become an attractive source of mesenchymal-like stem cells. Over the past decade, there have been numerous studies supporting the angiogenic, neuroprotective, and neurotrophic effects of the DSC secretome. Together with their ability to differentiate into endothelial cells and neural cell types, this makes DSCs suitable candidates for dental tissue engineering and nerve injury repair.
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