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Biomaterials for the Treatment and Diagnosis of Neurodegenerative Diseases

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

Deadline for manuscript submissions: closed (15 April 2020) | Viewed by 36918

Special Issue Editors

Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Avda. Joan XXIII, 27-31, 08028 Barcelona, Spain
Interests: colloids; micelles; layer-by-layer; liposomes; magnetic particles; drug delivery; magnetic hyperthermia; magnetic photothermia
Special Issues, Collections and Topics in MDPI journals
Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Avda. Joan XXIII, 27-31, 08028 Barcelona, Spain

Special Issue Information

Dear Colleagues,

This Special Issue “Biomaterials for the treatment and diagnosis of neurodegenerative diseases” will cover a selection of recent research topics on the applications of biomaterials in neurodegenerative diseases. In this way, this issue is dedicated to showing the interdisciplinary research encompassing elements of medicine, biology, chemistry, tissue engineering, and materials science. Among a large number of diseases, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative diseases. For instance, at present, more than 47 million people worldwide suffer from AD, and the number is predicted to exceed 130 million by 2050. Despite this importance, both diseases lack definite diagnostic approaches and an effective cure. As a consequence of the increasing prevalence of AD and PD and the low efficacy of current therapies, the development of treatment and diagnosis strategies have increased in the last years. The emerging field of biomaterials—and their relation with the nanotechnology—has promised new techniques to solve some of the AD/PD challenges. Nanotechnology uses engineered biomaterials or devices that can interact with biological systems at molecular levels with a high degree of specificity. Biomaterials are widely used in the fields of drug delivery, early diagnosis, and functional tissue engineering. One of the major problems with respect to the treatment and diagnosis of neurodegenerative diseases is to overcome the blood-brain barrier (BBB). Some biomaterials are able to cross the BBB, and this fact makes possible the increase of the drug availability in the central nervous systems, as well as the detection of biomarkers of neurodegenerative diseases in biological fluids.

We invite researchers to contribute original and review articles regarding the impact of Biomaterials in the treatment and diagnosis of neurodegenerative diseases. Potential topics include, but are not limited to, the following:

  • nanoparticles
  • liposomes
  • microparticles
  • scaffolds
  • nanodevices
  • nanosized chips
  • quantum dots

Prof. Dr. Joan Estelrich
Dr. Raimon Sabaté
Guest Editors

Manuscript Submission Information

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Published Papers (7 papers)

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Research

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19 pages, 5872 KiB  
Article
A Novel Zinc Chelator, 1H10, Ameliorates Experimental Autoimmune Encephalomyelitis by Modulating Zinc Toxicity and AMPK Activation
by Bo Young Choi, Jeong Hyun Jeong, Jae-Won Eom, Jae-Young Koh, Yang-Hee Kim and Sang Won Suh
Int. J. Mol. Sci. 2020, 21(9), 3375; https://doi.org/10.3390/ijms21093375 - 10 May 2020
Cited by 6 | Viewed by 3502
Abstract
Previous studies in our lab revealed that chemical zinc chelation or zinc transporter 3 (ZnT3) gene deletion suppresses the clinical features and neuropathological changes associated with experimental autoimmune encephalomyelitis (EAE). In addition, although protective functions are well documented for AMP-activated protein [...] Read more.
Previous studies in our lab revealed that chemical zinc chelation or zinc transporter 3 (ZnT3) gene deletion suppresses the clinical features and neuropathological changes associated with experimental autoimmune encephalomyelitis (EAE). In addition, although protective functions are well documented for AMP-activated protein kinase (AMPK), paradoxically, disease-promoting effects have also been demonstrated for this enzyme. Recent studies have demonstrated that AMPK contributes to zinc-induced neurotoxicity and that 1H10, an inhibitor of AMPK, reduces zinc-induced neuronal death and protects against oxidative stress, excitotoxicity, and apoptosis. Here, we sought to evaluate the therapeutic efficacy of 1H10 against myelin oligodendrocyte glycoprotein 35-55-induced EAE. 1H10 (5 μg/kg) was intraperitoneally injected once per day for the entire experimental course. Histological evaluation was performed three weeks after the initial immunization. We found that 1H10 profoundly reduced the severity of the induced EAE and that there was a remarkable suppression of demyelination, microglial activation, and immune cell infiltration. 1H10 also remarkably inhibited EAE-associated blood-brain barrier (BBB) disruption, MMP-9 activation, and aberrant synaptic zinc patch formation. Furthermore, the present study showed that long-term treatment with 1H10 also reduced the clinical course of EAE. Therefore, the present study suggests that zinc chelation and AMPK inhibition with 1H10 may have great therapeutic potential for the treatment of multiple sclerosis. Full article
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20 pages, 4097 KiB  
Article
Effects of the Pentapeptide P33 on Memory and Synaptic Plasticity in APP/PS1 Transgenic Mice: A Novel Mechanism Presenting the Protein Fe65 as a Target
by Titanilla Szögi, Ildikó Schuster, Emőke Borbély, Andrea Gyebrovszki, Zsolt Bozsó, János Gera, Róbert Rajkó, Miklós Sántha, Botond Penke and Lívia Fülöp
Int. J. Mol. Sci. 2019, 20(12), 3050; https://doi.org/10.3390/ijms20123050 - 22 Jun 2019
Cited by 10 | Viewed by 2975
Abstract
Regulated intramembrane proteolysis (RIP) of the amyloid precursor protein (APP) leads to the formation of fragments, among which the intracellular domain of APP (AICD) was also identified to be a causative of early pathological events. AICD-counteracting proteins, such as Fe65, may serve as [...] Read more.
Regulated intramembrane proteolysis (RIP) of the amyloid precursor protein (APP) leads to the formation of fragments, among which the intracellular domain of APP (AICD) was also identified to be a causative of early pathological events. AICD-counteracting proteins, such as Fe65, may serve as alternative therapeutic targets of Alzheimer’s disease (AD). The detection of elevated levels of Fe65 in the brains of both human patients and APP transgenic mice may further strengthen the hypothesis that influencing the interaction between Fe65 and APP may have a beneficial effect on the course of AD. Based on a PXP motif, proven to bind to the WW domain of Fe65, a new pentapeptide was designed and tested. The impedimental effect of P33 on the production of beta amyloid (Aβ) (soluble fraction and aggregated plaques) and on the typical features of the AD pathology (decreased dendritic spine density, synaptic markers, elevated inflammatory reactions) was also demonstrated. Significant enhancements of both learning ability and memory function were observed in a Morris water maze paradigm. The results led us to formulate the theory that P33 acts by altering the conformation of Fe65 via binding to its WW domain, consequently hindering any interactions between Fe65 and key members involved in APP processing. Full article
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15 pages, 2102 KiB  
Article
P3HT:Bebq2-Based Photovoltaic Device Enhances Differentiation of hiPSC-Derived Retinal Ganglion Cells
by Chih-Chen Hsu, Yi-Ying Lin, Tien-Chun Yang, Aliaksandr A. Yarmishyn, Tzu-Wei Lin, Yuh-Lih Chang, De-Kuang Hwang, Chien-Ying Wang, Yung-Yang Liu, Wen-Liang Lo, Chi-Hsien Peng, Shih-Jen Chen and Yi-Ping Yang
Int. J. Mol. Sci. 2019, 20(11), 2661; https://doi.org/10.3390/ijms20112661 - 30 May 2019
Cited by 6 | Viewed by 3081
Abstract
Electric field stimulation is known to affect various cellular processes, including cell fate specification and differentiation, particularly towards neuronal lineages. This makes it a promising therapeutic strategy to stimulate regeneration of neuronal tissues. Retinal ganglion cells (RGCs) is a type of neural cells [...] Read more.
Electric field stimulation is known to affect various cellular processes, including cell fate specification and differentiation, particularly towards neuronal lineages. This makes it a promising therapeutic strategy to stimulate regeneration of neuronal tissues. Retinal ganglion cells (RGCs) is a type of neural cells of the retina responsible for transduction of visual signals from the retina to the brain cortex, and is often degenerated in various blindness-causing retinal diseases. The organic photovoltaic materials such as poly-3-hexylthiophene (P3HT) can generate electric current upon illumination with light of the visible spectrum, and possesses several advantageous properties, including light weight, flexibility and high biocompatibility, which makes them a highly promising tool for electric stimulation of cells in vitro and in vivo. In this study, we tested the ability to generate photocurrent by several formulations of blend (bulk heterojunction) of P3HT (which is electron donor material) with several electron acceptor materials, including Alq3 and bis(10-hydroxybenzo[h]quinolinato)beryllium (Bebq2). We found that the photovoltaic device based on bulk heterojunction of P3HT with Bebq2 could generate photocurrent when illuminated by both green laser and visible spectrum light. We tested the growth and differentiation capacity of human induced pluripotent stem cells (hiPSC)-derived RGCs when grown in interface with such photostimulated device, and found that they were significantly increased. The application of P3HT:Bebq2-formulation of photovoltaic device has a great potential for developments in retinal transplantation, nerve repair and tissue engineering approaches of treatment of retinal degeneration. Full article
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Review

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28 pages, 2409 KiB  
Review
Nanotechnology Therapy for Alzheimer′s Disease Memory Impairment Attenuation
by Samo Ribarič
Int. J. Mol. Sci. 2021, 22(3), 1102; https://doi.org/10.3390/ijms22031102 - 22 Jan 2021
Cited by 2 | Viewed by 2908
Abstract
Currently, there is no cure for Alzheimer’s disease (AD) in humans; treatment is symptomatic only. Aging of the population, together with an unhealthy diet and lifestyle, contribute to the steady, global increase of AD patients. This increase creates significant health, societal and economical [...] Read more.
Currently, there is no cure for Alzheimer’s disease (AD) in humans; treatment is symptomatic only. Aging of the population, together with an unhealthy diet and lifestyle, contribute to the steady, global increase of AD patients. This increase creates significant health, societal and economical challenges even for the most developed countries. AD progresses from an asymptomatic stage to a progressively worsening cognitive impairment. The AD cognitive impairment is underpinned by progressive memory impairment, an increasing inability to recall recent events, to execute recently planned actions, and to learn. These changes prevent the AD patient from leading an independent and fulfilling life. Nanotechnology (NT) enables a new, alternative pathway for development of AD treatment interventions. At present, the NT treatments for attenuation of AD memory impairment are at the animal model stage. Over the past four years, there has been a steady increase in publications of AD animal models with a wide variety of original NT treatment interventions, able to attenuate memory impairment. NT therapy development, in animal models of AD, is faced with the twin challenges of the nature of AD, a chronic impairment, unique to human, of the tau protein and A β peptides that regulate several key physiological brain processes, and the incomplete understanding of AD′s aetiology. This paper reviews the state-of-the-art in NT based treatments for AD memory impairment in animal models and discusses the future work for translation to the successful treatment of AD cognitive impairment in human. Full article
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21 pages, 534 KiB  
Review
Challenges in Biomaterial-Based Drug Delivery Approach for the Treatment of Neurodegenerative Diseases: Opportunities for Extracellular Vesicles
by Asit Kumar, Lina Zhou, Kaining Zhi, Babatunde Raji, Shelby Pernell, Erene Tadrous, Sunitha Kodidela, Anantha Nookala, Harry Kochat and Santosh Kumar
Int. J. Mol. Sci. 2021, 22(1), 138; https://doi.org/10.3390/ijms22010138 - 25 Dec 2020
Cited by 22 | Viewed by 5574
Abstract
Biomaterials have been the subject of numerous studies to pursue potential therapeutic interventions for a wide variety of disorders and diseases. The physical and chemical properties of various materials have been explored to develop natural, synthetic, or semi-synthetic materials with distinct advantages for [...] Read more.
Biomaterials have been the subject of numerous studies to pursue potential therapeutic interventions for a wide variety of disorders and diseases. The physical and chemical properties of various materials have been explored to develop natural, synthetic, or semi-synthetic materials with distinct advantages for use as drug delivery systems for the central nervous system (CNS) and non-CNS diseases. In this review, an overview of popular biomaterials as drug delivery systems for neurogenerative diseases is provided, balancing the potential and challenges associated with the CNS drug delivery. As an effective drug delivery system, desired properties of biomaterials are discussed, addressing the persistent challenges such as targeted drug delivery, stimuli responsiveness, and controlled drug release in vivo. Finally, we discuss the prospects and limitations of incorporating extracellular vesicles (EVs) as a drug delivery system and their use for biocompatible, stable, and targeted delivery with limited immunogenicity, as well as their ability to be delivered via a non-invasive approach for the treatment of neurodegenerative diseases. Full article
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21 pages, 405 KiB  
Review
Biomaterials in Neurodegenerative Disorders: A Promising Therapeutic Approach
by Matteo Bordoni, Eveljn Scarian, Federica Rey, Stella Gagliardi, Stephana Carelli, Orietta Pansarasa and Cristina Cereda
Int. J. Mol. Sci. 2020, 21(9), 3243; https://doi.org/10.3390/ijms21093243 - 04 May 2020
Cited by 47 | Viewed by 5953
Abstract
Neurodegenerative disorders (i.e., Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and spinal cord injury) represent a great problem worldwide and are becoming prevalent because of the increasing average age of the population. Despite many studies having focused on their etiopathology, the exact cause [...] Read more.
Neurodegenerative disorders (i.e., Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and spinal cord injury) represent a great problem worldwide and are becoming prevalent because of the increasing average age of the population. Despite many studies having focused on their etiopathology, the exact cause of these diseases is still unknown and until now, there are only symptomatic treatments. Biomaterials have become important not only for the study of disease pathogenesis, but also for their application in regenerative medicine. The great advantages provided by biomaterials are their ability to mimic the environment of the extracellular matrix and to allow the growth of different types of cells. Biomaterials can be used as supporting material for cell proliferation to be transplanted and as vectors to deliver many active molecules for the treatments of neurodegenerative disorders. In this review, we aim to report the potentiality of biomaterials (i.e., hydrogels, nanoparticles, self-assembling peptides, nanofibers and carbon-based nanomaterials) by analyzing their use in the regeneration of neural and glial cells their role in axon outgrowth. Although further studies are needed for their use in humans, the promising results obtained by several groups leads us to suppose that biomaterials represent a potential therapeutic approach for the treatments of neurodegenerative disorders. Full article
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26 pages, 1130 KiB  
Review
Review of Current Strategies for Delivering Alzheimer’s Disease Drugs across the Blood-Brain Barrier
by Ka Hong Wong, Muhammad Kashif Riaz, Yuning Xie, Xue Zhang, Qiang Liu, Huoji Chen, Zhaoxiang Bian, Xiaoyu Chen, Aiping Lu and Zhijun Yang
Int. J. Mol. Sci. 2019, 20(2), 381; https://doi.org/10.3390/ijms20020381 - 17 Jan 2019
Cited by 127 | Viewed by 12153
Abstract
Effective therapy for Alzheimer’s disease is a major challenge in the pharmaceutical sciences. There are six FDA approved drugs (e.g., donepezil, memantine) that show some effectiveness; however, they only relieve symptoms. Two factors hamper research. First, the cause of Alzheimer’s disease is not [...] Read more.
Effective therapy for Alzheimer’s disease is a major challenge in the pharmaceutical sciences. There are six FDA approved drugs (e.g., donepezil, memantine) that show some effectiveness; however, they only relieve symptoms. Two factors hamper research. First, the cause of Alzheimer’s disease is not fully understood. Second, the blood-brain barrier restricts drug efficacy. This review summarized current knowledge relevant to both of these factors. First, we reviewed the pathophysiology of Alzheimer’s disease. Next, we reviewed the structural and biological properties of the blood-brain barrier. We then described the most promising drug delivery systems that have been developed in recent years; these include polymeric nanoparticles, liposomes, metallic nanoparticles and cyclodextrins. Overall, we aim to provide ideas and clues to design effective drug delivery systems for penetrating the blood-brain barrier to treat Alzheimer’s disease. Full article
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