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Biomaterials, Neuroimmunology and Stem Cells for Repair Strategies in the Central Nervous System

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 16735

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Special Issue Editors

Prof. Dr. Zin Z. Khaing

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Guest Editor

Department of Neurological Surgery, University of Washington, Brotman Baty Institute for Precision Medicine, Institute for Stem Cell & Regenerative Medicine, Washington, USA
Interests: neurodegenerative diseases; neuroinflammation; stem cells; spinal cord injury; engineered biomaterials

Prof. Dr. Stephanie Seidlits

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Guest Editor

Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, USA

Special Issue Information

Dear Colleagues,

Advances in stem cell biology and the development of novel biomaterials have changed the landscape of repair strategies for the central nervous system. Biomaterials made from synthetic as well as natural based materials applied to the central nervous system with engineering design components with specialized topography, pore size and bioactive molecules have been explored. Stem cells, either alone or in combination with biomaterials, have also been applied to promote the regeneration of brain and spinal cord tissues. It is becoming clear is that the neuroimmune system will likely play a critical role in the successful integration of exogenous biomaterials and stem cells, either alone or in combination, as part of a repair strategy.

In this Special Issue, focusing on the neuroimmune reaction to biomaterials and stem cells for CNS repair, we invite authors to contribute their original research articles, reviews and opinion letters.

Prof. Dr. Zin Z. Khaing
Prof. Dr. Stephanie Seidlits
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

central nervous system
biomaterials
stem cells
neuroimmunology

Published Papers (5 papers)

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Research

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23 pages, 8417 KiB

Open AccessArticle

Post-Stroke Timing of ECM Hydrogel Implantation Affects Biodegradation and Tissue Restoration

by Corina Damian, Harmanvir Ghuman, Carrinton Mauney, Reem Azar, Janina Reinartz, Stephen F. Badylak and Michel Modo

Int. J. Mol. Sci. 2021, 22(21), 11372; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111372 - 21 Oct 2021

Cited by 11 | Viewed by 3021

Abstract

Extracellular matrix (ECM) hydrogel promotes tissue regeneration in lesion cavities after stroke. However, a bioscaffold’s regenerative potential needs to be considered in the context of the evolving pathological environment caused by a stroke. To evaluate this key issue in rats, ECM hydrogel was delivered to the lesion core/cavity at 7-, 14-, 28-, and 90-days post-stroke. Due to a lack of tissue cavitation 7-days post-stroke, implantation of ECM hydrogel did not achieve a sufficient volume and distribution to warrant comparison with the other time points. Biodegradation of ECM hydrogel implanted 14- and 28-days post-stroke were efficiently (80%) degraded by 14-days post-bioscaffold implantation, whereas implantation 90-days post-stroke revealed only a 60% decrease. Macrophage invasion was robust at 14- and 28-days post-stroke but reduced in the 90-days post-stroke condition. The pro-inflammation (M1) and pro-repair (M2) phenotype ratios were equivalent at all time points, suggesting that the pathological environment determines macrophage invasion, whereas ECM hydrogel defines their polarization. Neural cells (neural progenitors, neurons, astrocytes, oligodendrocytes) were found at all time points, but a 90-days post-stroke implantation resulted in reduced densities of mature phenotypes. Brain tissue restoration is therefore dependent on an efficient delivery of a bioscaffold to a tissue cavity, with 28-days post-stroke producing the most efficient biodegradation and tissue regeneration, whereas by 90-days post-stroke, these effects are significantly reduced. Improving our understanding of how the pathological environment influences biodegradation and the tissue restoration process is hence essential to devise engineering strategies that could extend the therapeutic window for bioscaffolds to repair the damaged brain. Full article

(This article belongs to the Special Issue Biomaterials, Neuroimmunology and Stem Cells for Repair Strategies in the Central Nervous System)

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Review

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24 pages, 1137 KiB

Open AccessReview

Neurotrophic Factors as Regenerative Therapy for Neurodegenerative Diseases: Current Status, Challenges and Future Perspectives

by Yousra El Ouaamari, Jasper Van den Bos, Barbara Willekens, Nathalie Cools and Inez Wens

Int. J. Mol. Sci. 2023, 24(4), 3866; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24043866 - 15 Feb 2023

Cited by 12 | Viewed by 3117

Abstract

Neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), multiple sclerosis (MS), spinal cord injury (SCI), and amyotrophic lateral sclerosis (ALS), are characterized by acute or chronic progressive loss of one or several neuronal subtypes. However, despite their increasing prevalence, little progress has been made in successfully treating these diseases. Research has recently focused on neurotrophic factors (NTFs) as potential regenerative therapy for neurodegenerative diseases. Here, we discuss the current state of knowledge, challenges, and future perspectives of NTFs with a direct regenerative effect in chronic inflammatory and degenerative disorders. Various systems for delivery of NTFs, such as stem and immune cells, viral vectors, and biomaterials, have been applied to deliver exogenous NTFs to the central nervous system, with promising results. The challenges that currently need to be overcome include the amount of NTFs delivered, the invasiveness of the delivery route, the blood–brain barrier permeability, and the occurrence of side effects. Nevertheless, it is important to continue research and develop standards for clinical applications. In addition to the use of single NTFs, the complexity of chronic inflammatory and degenerative diseases may require combination therapies targeting multiple pathways or other possibilities using smaller molecules, such as NTF mimetics, for effective treatment. Full article

(This article belongs to the Special Issue Biomaterials, Neuroimmunology and Stem Cells for Repair Strategies in the Central Nervous System)

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45 pages, 2026 KiB

Open AccessReview

Clinical Trials Targeting Secondary Damage after Traumatic Spinal Cord Injury

by Zin Z. Khaing, Jessica Y. Chen, Gevick Safarians, Sohib Ezubeik, Nicolas Pedroncelli, Rebecca D. Duquette, Tobias Prasse and Stephanie K. Seidlits

Int. J. Mol. Sci. 2023, 24(4), 3824; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24043824 - 14 Feb 2023

Cited by 11 | Viewed by 2680

Abstract

Spinal cord injury (SCI) often causes loss of sensory and motor function resulting in a significant reduction in quality of life for patients. Currently, no therapies are available that can repair spinal cord tissue. After the primary SCI, an acute inflammatory response induces further tissue damage in a process known as secondary injury. Targeting secondary injury to prevent additional tissue damage during the acute and subacute phases of SCI represents a promising strategy to improve patient outcomes. Here, we review clinical trials of neuroprotective therapeutics expected to mitigate secondary injury, focusing primarily on those in the last decade. The strategies discussed are broadly categorized as acute-phase procedural/surgical interventions, systemically delivered pharmacological agents, and cell-based therapies. In addition, we summarize the potential for combinatorial therapies and considerations. Full article

(This article belongs to the Special Issue Biomaterials, Neuroimmunology and Stem Cells for Repair Strategies in the Central Nervous System)

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25 pages, 1422 KiB

Open AccessReview

Clickable Biomaterials for Modulating Neuroinflammation

by Chase Cornelison and Sherly Fadel

Int. J. Mol. Sci. 2022, 23(15), 8496; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158496 - 31 Jul 2022

Viewed by 3510

Abstract

Crosstalk between the nervous and immune systems in the context of trauma or disease can lead to a state of neuroinflammation or excessive recruitment and activation of peripheral and central immune cells. Neuroinflammation is an underlying and contributing factor to myriad neuropathologies including neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease; autoimmune diseases like multiple sclerosis; peripheral and central nervous system infections; and ischemic and traumatic neural injuries. Therapeutic modulation of immune cell function is an emerging strategy to quell neuroinflammation and promote tissue homeostasis and/or repair. One such branch of ‘immunomodulation’ leverages the versatility of biomaterials to regulate immune cell phenotypes through direct cell-material interactions or targeted release of therapeutic payloads. In this regard, a growing trend in biomaterial science is the functionalization of materials using chemistries that do not interfere with biological processes, so-called ‘click’ or bioorthogonal reactions. Bioorthogonal chemistries such as Michael-type additions, thiol-ene reactions, and Diels-Alder reactions are highly specific and can be used in the presence of live cells for material crosslinking, decoration, protein or cell targeting, and spatiotemporal modification. Hence, click-based biomaterials can be highly bioactive and instruct a variety of cellular functions, even within the context of neuroinflammation. This manuscript will review recent advances in the application of click-based biomaterials for treating neuroinflammation and promoting neural tissue repair. Full article

(This article belongs to the Special Issue Biomaterials, Neuroimmunology and Stem Cells for Repair Strategies in the Central Nervous System)

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22 pages, 3379 KiB

Open AccessReview

Novel Strategies for Spinal Cord Regeneration

by Bogdan Costăchescu, Adelina-Gabriela Niculescu, Marius Gabriel Dabija, Raluca Ioana Teleanu, Alexandru Mihai Grumezescu and Lucian Eva

Int. J. Mol. Sci. 2022, 23(9), 4552; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23094552 - 20 Apr 2022

Cited by 13 | Viewed by 3617

Abstract

A spinal cord injury (SCI) is one of the most devastating lesions, as it can damage the continuity and conductivity of the central nervous system, resulting in complex pathophysiology. Encouraged by the advances in nanotechnology, stem cell biology, and materials science, researchers have proposed various interdisciplinary approaches for spinal cord regeneration. In this respect, the present review aims to explore the most recent developments in SCI treatment and spinal cord repair. Specifically, it briefly describes the characteristics of SCIs, followed by an extensive discussion on newly developed nanocarriers (e.g., metal-based, polymer-based, liposomes) for spinal cord delivery, relevant biomolecules (e.g., growth factors, exosomes) for SCI treatment, innovative cell therapies, and novel natural and synthetic biomaterial scaffolds for spinal cord regeneration. Full article

(This article belongs to the Special Issue Biomaterials, Neuroimmunology and Stem Cells for Repair Strategies in the Central Nervous System)

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