scholarly journals The Use of Hydrogel-Delivered Extracellular Vesicles in Recovery of Motor Function in Stroke: A Testable Experimental Hypothesis for Clinical Translation including Behavioral and Neuroimaging Assessment Approaches

2020 ◽  
Author(s):  
Magdalini Tsintou ◽  
Kyriakos Dalamagkas ◽  
Tara L Moore ◽  
Yogesh Rathi ◽  
Marek Kubicki ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Extracellular Vesicles ◽  
Neural Tissue ◽  
Clinical Translation ◽  
Neural Repair ◽  
Cns Repair ◽  
Structural Support ◽  
Working Together ◽  
The Brain

Neural tissue engineering, nanotechnology and neuroregeneration are diverse biomedical disciplines that have been working together in recent decades to solve the complex problems linked to central nervous system (CNS) repair. It is known that the CNS demonstrates a very limited regenerative capacity because of a microenvironment that impedes effective regenerative processes, making development of CNS therapeutics challenging. Given the high prevalence of CNS conditions such as stroke that damage the brain and place a severe burden on afflicted individuals and on society, it is of utmost significance to explore the optimum methodologies for finding treatments that could be applied to humans for restoration of function to pre-injury levels. Extracellular vesicles (EVs), also known as exosomes, when derived from mesenchymal stem cells, are one of the most promising approaches that have been attempted thus far, as EVs deliver factors that stimulate recovery by acting at the nanoscale level on intercellular communication while avoiding the risks linked to stem cell transplantation. At the same time, advances in tissue engineering and regenerative medicine have offered the potential of using hydrogels as bio-scaffolds in order to provide the stroma required for neural repair to occur, as well as the release of biomolecules facilitating or inducing the reparative processes. This review introduces a novel experimental hypothesis regarding the benefits that could be offered if EVs were to be combined with biocompatible injectable hydrogels. The rationale behind this hypothesis is presented, analyzing how a hydrogel might prolong the retention of EVs and maximize the localized benefit to the brain. This sustained delivery of EVs would be coupled with essential guidance cues and structural support from the hydrogel until neural tissue remodeling and regeneration occur. Finally, the importance of including non-human primate (NHP) models in the clinical translation pipeline, as well as the added benefit of multi-modal neuroimage analysis to establish non-invasive, in vivo, quantifiable imaging-based biomarkers for CNS repair are discussed, aiming for more effective and safe clinical translation of such regenerative therapies to humans.

Optimization of Oxygen Delivery within Hydrogels

2021 ◽  
Author(s):  
Sophia M Mavris ◽  
Laura M Hansen
Keyword(s):  
Tissue Engineering ◽  
Oxygen Transport ◽  
Current Medical ◽  
The Body ◽  
Clinical Translation ◽  
Technological Innovations ◽  
Technological Advances ◽  
Cell Sources

Abstract The field of tissue engineering has been continuously evolving since its inception over three decades ago with numerous new advancements in biomaterials and cell sources and widening applications to most tissues in the body. Despite the substantial promise and great opportunities for the advancement of current medical therapies and procedures, the field has yet to capture wide clinical translation due to some remaining challenges, including oxygen availability within constructs, both in vitro and in vivo. While this insufficiency of nutrients, specifically oxygen, is a limitation within the current frameworks of this field, the literature shows promise in new technological advances to efficiently provide adequate delivery of nutrients to cells. This review attempts to capture the most recent advances in the field of oxygen transport in hydrogel-based tissue engineering, including a comparison of current research as it pertains to the modeling, sensing, and optimization of oxygen within hydrogel constructs as well as new technological innovations to overcome traditional diffusion-based limitations. The application of these findings can further the advancement and development of better hydrogel-based tissue engineered constructs for future clinical translation and adoption.

scholarly journals Repositioning N-Acetylcysteine (NAC): NAC-Loaded Electrospun Drug Delivery Scaffolding for Potential Neural Tissue Engineering Application

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 934
Author(s):  
Gillian D. Mahumane ◽  
Pradeep Kumar ◽  
Viness Pillay ◽  
Yahya E. Choonara
Keyword(s):  
Cell Viability ◽  
Engineering Application ◽  
Neural Tissue ◽  
Modern Medicine ◽  
Burst Release ◽  
Tissue Engineering Application ◽  
Glioblastoma Multiform ◽  
Pheochromocytoma Pc12 ◽  
The Brain

Traumatic brain injury (TBI) presents a serious challenge for modern medicine due to the poor regenerative capabilities of the brain, complex pathophysiology, and lack of effective treatment for TBI to date. Tissue-engineered scaffolds have shown some experimental success in vivo; unfortunately, none have yielded consummate results of clinical efficacy. N-acetylcysteine has shown neuroprotective potential. To this end, we developed a N-acetylcysteine (NAC)-loaded poly(lactic-co-glycolic acid) (PLGA) electrospun system for potential neural tissue application for TBI. Scanning electron microscopy showed nanofiber diameters ranging 72–542 nm and 124–592 nm for NAC-free and NAC-loaded PLGA nanofibers, respectively. NAC loading was obtained at 28%, and drug entrapment efficacy was obtained at 84%. A biphasic NAC release pattern that featured an initial burst release (13.9%) stage and a later sustained release stage was noted, thus enabling the prolonged replenishing of NAC and drastically improving cell viability and proliferation. This was evidenced by a significantly higher cell viability and proliferation on NAC-loaded nanofibers for rat pheochromocytoma (PC12) and human glioblastoma multiform (A172) cell lines in comparison to PLGA-only nanofibers. The increased cell viability and cell proliferation on NAC-loaded nanofiber substantiates for the repositioning of NAC as a pharmacological agent in neural tissue regeneration applications.

scholarly journals Blowing up Neural Repair for Stroke Recovery

Stroke ◽  
2020 ◽  
Vol 51 (10) ◽  
pp. 3169-3173
Author(s):  
Nick S. Ward ◽  
S. Thomas Carmichael
Keyword(s):  
Clinical Trials ◽  
Clinical Translation ◽  
Stroke Recovery ◽  
Preclinical Studies ◽  
Neural Repair ◽  
Biological Targets ◽  
Blowing Up ◽  
Biological Target ◽  
Multicenter Clinical Trials ◽  
The Brain

The repair and recovery of the brain after stroke is a field that is emerging in its preclinical science and clinical trials. However, recent large, multicenter clinical trials have been negative, and conflicting results emerge on biological targets in preclinical studies. The coalescence of negative clinical translation and confusion in preclinical studies raises the suggestion that perhaps the field of stroke recovery faces a fate similar to stroke neuroprotection, with interesting science ultimately proving difficult to translate to the clinic. This review highlights improvements in 4 areas of the stroke neural repair field that should reorient the field toward successful clinical translation: improvements in rodent genetic models of stroke recovery, consideration of the biological target in stroke recovery, stratification in clinical trials, and the use of appropriate clinical trial end points.

scholarly journals JC Polyomavirus Uses Extracellular Vesicles To Infect Target Cells

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Jenna Morris-Love ◽  
Gretchen V. Gee ◽  
Bethany A. O’Hara ◽  
Benedetta Assetta ◽  
Abigail L. Atkinson ◽  
...  
Keyword(s):  
Progressive Multifocal Leukoencephalopathy ◽  
Extracellular Vesicles ◽  
Critical Role ◽  
Outer Side ◽  
Target Cells ◽  
Alternative Mechanism ◽  
Jc Polyomavirus ◽  
Virus Receptors ◽  
The Brain

ABSTRACTThe endemic human JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy in immune-suppressed patients. The mechanisms of virus infectionin vivoare not understood because the major target cells for virus in the brain do not express virus receptors and do not bind virus. We found that JCPyV associates with extracellular vesicles (EVs) and can infect target cells independently of virus receptors. Virus particles were found packaged inside extracellular vesicles and attached to the outer side of vesicles. Anti-JCPyV antisera reduced infection by purified virus but had no effect on infection by EV-associated virus. Treatment of cells with the receptor-destroying enzyme neuraminidase inhibited infection with purified virus but did not inhibit infection by EV-associated virus. Mutant pseudoviruses defective in sialic acid receptor binding could not transduce cells as purified pseudovirions but could do so when associated with EVs. This alternative mechanism of infection likely plays a critical role in the dissemination and spread of JCPyV both to and within the central nervous system.IMPORTANCEJC polyomavirus (JCPyV) is a ubiquitous human pathogen that causes progressive multifocal leukoencephalopathy (PML), a severe and often fatal neurodegenerative disease in immunocompromised or immunomodulated patients. The mechanisms responsible for initiating infection in susceptible cells are not completely known. The major attachment receptor for the virus, lactoseries tetrasaccharide c (LSTc), is paradoxically not expressed on oligodendrocytes or astrocytes in human brain, and virus does not bind to these cells. Because these are the major cell types targeted by the virus in the brain, we hypothesized that alternative mechanisms of infection must be responsible. Here we provide evidence that JCPyV is packaged in extracellular vesicles from infected cells. Infection of target cells by vesicle-associated virus is not dependent on LSTc and is not neutralized by antisera directed against the virus. This is the first demonstration of a polyomavirus using extracellular vesicles as a means of transmission.

In vivo neural tissue engineering using adipose-derived mesenchymal stem cells and fibrin matrix

2021 ◽  
pp. 1-15
Author(s):  
Krishnapriya Chandrababu ◽  
Harikrishnan Vijayakumar Sreelatha ◽  
Tara Sudhadevi ◽  
Arya Anil ◽  
Sabareeswaran Arumugam ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Neural Tissue ◽  
Neural Tissue Engineering ◽  
Fibrin Matrix

Recent Development in the Fabrication of Collagen Scaffolds for Tissue Engineering Applications: A Review

2019 ◽  
Vol 20 (12) ◽  
pp. 992-1003 ◽  
Author(s):  
Mohammad F. Mh Busra ◽  
Yogeswaran Lokanathan
Keyword(s):  
Tissue Engineering ◽  
Ex Vivo ◽  
Physicochemical Characteristics ◽  
Collagen Scaffolds ◽  
Engineering Applications ◽  
Hydrogel Beads ◽  
Structural Support ◽  
Main Components ◽  
Sheet Membrane

Tissue engineering focuses on developing biological substitutes to restore, maintain or improve tissue functions. The three main components of its application are scaffold, cell and growthstimulating signals. Scaffolds composed of biomaterials mainly function as the structural support for ex vivo cells to attach and proliferate. They also provide physical, mechanical and biochemical cues for the differentiation of cells before transferring to the in vivo site. Collagen has been long used in various clinical applications, including drug delivery. The wide usage of collagen in the clinical field can be attributed to its abundance in nature, biocompatibility, low antigenicity and biodegradability. In addition, the high tensile strength and fibril-forming ability of collagen enable its fabrication into various forms, such as sheet/membrane, sponge, hydrogel, beads, nanofibre and nanoparticle, and as a coating material. The wide option of fabrication technology together with the excellent biological and physicochemical characteristics of collagen has stimulated the use of collagen scaffolds in various tissue engineering applications. This review describes the fabrication methods used to produce various forms of scaffolds used in tissue engineering applications.

scholarly journals Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Potential

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ashley G. Zhao ◽  
Kiran Shah ◽  
Brett Cromer ◽  
Huseyin Sumer
Keyword(s):  
Tissue Engineering ◽  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Target Cells ◽  
Therapeutic Effects ◽  
Multipotent Cells ◽  
Membrane Bound

Extracellular vesicles (EVs) are cell-derived membrane-bound nanoparticles, which act as shuttles, delivering a range of biomolecules to diverse target cells. They play an important role in maintenance of biophysiological homeostasis and cellular, physiological, and pathological processes. EVs have significant diagnostic and therapeutic potentials and have been studied both in vitro and in vivo in many fields. Mesenchymal stem cells (MSCs) are multipotent cells with many therapeutic applications and have also gained much attention as prolific producers of EVs. MSC-derived EVs are being explored as a therapeutic alternative to MSCs since they may have similar therapeutic effects but are cell-free. They have applications in regenerative medicine and tissue engineering and, most importantly, confer several advantages over cells such as lower immunogenicity, capacity to cross biological barriers, and less safety concerns. In this review, we introduce the biogenesis of EVs, including exosomes and microvesicles. We then turn more specifically to investigations of MSC-derived EVs. We highlight the great therapeutic potential of MSC-derived EVs and applications in regenerative medicine and tissue engineering.

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