Self-assembling peptide hydrogels for the stabilization and sustained release of active Chondroitinase ABC in vitro and in spinal cord injuries

2020 ◽  
Author(s):  
Andrea Raspa ◽  
Luisa Carminati ◽  
Raffaele Pugliese ◽  
Federico Fontana ◽  
Fabrizio Gelain
Keyword(s):  
Spinal Cord ◽  
Sustained Release ◽  
Spinal Cord Injuries ◽  
Chondroitinase Abc ◽  
Self Assembling ◽  
Peptide Hydrogels

Evaluation of in situ gelling chitosan-PEG copolymer for use in the spinal cord

2018 ◽  
Vol 33 (3) ◽  
pp. 435-446 ◽  
Author(s):  
Ashley E Mohrman ◽  
Mahmoud Farrag ◽  
Rachel K Grimm ◽  
Nic D Leipzig
Keyword(s):  
Spinal Cord ◽  
Polyethylene Glycol ◽  
Spinal Cord Injuries ◽  
Similar Response ◽  
Cellular Delivery ◽  
Thiolated Chitosan ◽  
Cord Injury ◽  
In Situ Gelling

The goal of the present work was to characterize a hydrogel material for localized spinal cord delivery. To address spinal cord injuries, an injectable in situ gelling system was tested utilizing a simple, effective, and rapid cross-linking method via Michael addition. Thiolated chitosan material and maleimide-terminated polyethylene glycol material were mixed to form a hydrogel and evaluated in vitro and in vivo. Three distinct thiolated chitosan precursors were made by varying reaction conditions; a modification of chitosan with Traut’s reagent (2-iminothiolane) displayed the most attractive hydrogel properties once mixed with polyethylene glycol. The final hydrogel chosen for animal testing had a swelling ratio (Q) of 57.5 ± 3.4 and elastic modulus of 378 ± 72 Pa. After confirming low cellular toxicity in vitro, the hydrogel was injected into the spinal cord of rats for 1 and 2 weeks to assess host reaction. The rats displayed no overt functional deficits due to injection following initial surgical recovery and throughout the 2-week period after for both the saline-injected sham group and hydrogel-injected group. The saline and hydrogel-injected animals both showed a similar response from ED1+ microglia and GFAP overexpression. No significant differences were found between saline-injected and hydrogel-injected groups for any of the measures studied, but there was a trend toward decreased affected area size from 1 to 2 weeks in both groups. Access to the central nervous system is limited by the blood–brain barrier for noninvasive therapies; further development of the current system for localized drug or cellular delivery has the potential to shape treatments of spinal cord injury.

scholarly journals Multifunctionalized hydrogels foster hNSC maturation in 3D cultures and neural regeneration in spinal cord injuries

2019 ◽  
Vol 116 (15) ◽  
pp. 7483-7492 ◽  
Author(s):  
Amanda Marchini ◽  
Andrea Raspa ◽  
Raffaele Pugliese ◽  
Marina Abd El Malek ◽  
Valentina Pastori ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Culture Media ◽  
Three Dimensional ◽  
Cholinergic Neurons ◽  
Good Manufacturing Practice ◽  
Neural Regeneration ◽  
Neuronal Markers

Three-dimensional cell cultures are leading the way to the fabrication of tissue-like constructs useful to developmental biology and pharmaceutical screenings. However, their reproducibility and translational potential have been limited by biomaterial and culture media compositions, as well as cellular sources. We developed a construct comprising synthetic multifunctionalized hydrogels, serum-free media, and densely seeded good manufacturing practice protocol-grade human neural stem cells (hNSC). We tracked hNSC proliferation, differentiation, and maturation into GABAergic, glutamatergic, and cholinergic neurons, showing entangled electrically active neural networks. The neuroregenerative potential of the “engineered tissue” was assessed in spinal cord injuries, where hNSC-derived progenitors and predifferentiated hNSC progeny, embedded in multifunctionalized hydrogels, were implanted. All implants decreased astrogliosis and lowered the immune response, but scaffolds with predifferentiated hNSCs showed higher percentages of neuronal markers, better hNSC engraftment, and improved behavioral recovery. Our hNSC-construct enables the formation of 3D functional neuronal networks in vitro, allowing novel strategies for hNSC therapies in vivo.

scholarly journals Self-Assembling Peptide Hydrogels Modulate In Vitro Chondrogenesis of Bovine Bone Marrow Stromal Cells

2010 ◽  
Vol 16 (2) ◽  
pp. 465-477 ◽  
Author(s):  
Paul W. Kopesky ◽  
Eric J. Vanderploeg ◽  
John S. Sandy ◽  
Bodo Kurz ◽  
Alan J. Grodzinsky
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Bovine Bone ◽  
Self Assembling ◽  
Peptide Hydrogels

scholarly journals CCP1, a tubulin deglutamylase, increases survival of rodent spinal cord neurons following glutamate-induced excitotoxicity

2020 ◽  
Author(s):  
Yasmin H. Ramadan ◽  
Amanda Gu ◽  
Nicole Ross ◽  
Sara A. McEwan ◽  
Maureen M. Barr ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Intracellular Transport ◽  
Spinal Cord Injuries ◽  
Neuronal Injury ◽  
Post Translational Modification ◽  
Spinal Cord Neurons ◽  
C Elegans ◽  
Structural Support ◽  
Cytoskeletal Elements

AbstractMicrotubules (MTs) are cytoskeletal elements that provide structural support, establish morphology, and act as roadways for intracellular transport in cells. Neurons extend and must maintain long axons and dendrites to transmit information through the nervous system. Therefore, in neurons, the ability to independently regulate cytoskeletal stability and MT-based transport in different cellular compartments is essential. Post-translational modification of MTs is one mechanism by which neurons can regulate the cytoskeleton.The carboxypeptidase CCP1 negatively regulates post-translational glutamylation of MTs. We previously demonstrated that the CCP1 homolog in C. elegans is important for maintenance of cilia. In mammals, loss of CCP1, and the resulting hyperglutamylation of MTs, causes neurodegeneration. It has long been known that CCP1 expression is activated by neuronal injury; however, whether CCP1 plays a neuroprotective role after injury is unknown. Furthermore, it not yet clear whether CCP1 acts on ciliary MTs in spinal cord neurons.Using an in vitro model of excitotoxic neuronal injury coupled with shRNA-mediated knockdown of CCP1, we demonstrate that CCP1 protects neurons from excitotoxic death. Unexpectedly, excitotoxic injury reduced CCP1 expression in our system, and knockdown of CCP1 did not result in loss or shortening of cilia in cultured spinal cord neurons. Our results suggest that CCP1 acts on axonal and dendritic MTs to promote cytoskeletal rearrangements that support neuroregeneration and that enzymes responsible for glutamylation of MTs might be therapeutically targeted to prevent excitotoxic death after spinal cord injuries.

scholarly journals Comparing natural hydrogels to self-assembling peptides in spinal cord injury treatment: a systematic review

F1000Research ◽  
2022 ◽  
Vol 11 ◽  
pp. 16
Author(s):  
Kurosh Mojtabavi ◽  
Morteza Gholami ◽  
Zahra Ghodsi ◽  
Narges Mahmoodi ◽  
Sina Shool ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Data Extraction ◽  
Included Study ◽  
Cns Injury ◽  
Neuronal Regeneration ◽  
Self Assembling ◽  
Cord Injury ◽  
Injury Treatment

Background: In many cases, central nervous system (CNS) injury is unchanging due to the absence of neuronal regeneration and repair capabilities. In recent years, regenerative medicine, and especially hydrogels, has reached a significant amount of attention for their promising results for the treatment of spinal cord injury (SCI) currently considered permanent. Hydrogels are categorized based on their foundation: synthetic, natural, and combination. The objective of this study was to compare the properties and efficacy of commonly used hydrogels, like collagen, and other natural peptides with synthetic self-assembling peptide hydrogels in the treatment of SCI.  Methods: Articles were searched in PubMed, Scopus, Web of Science, and Embase. All studies from 1985 until January 2020 were included in the primary search. Eligible articles were included based on the following criteria: administering hydrogels (both natural and synthetic) for SCI treatment, solely focusing on spinal cord injury treatment, and published in a peer-reviewed journal. Data on axonal regeneration, revascularization, elasticity, drug delivery efficacy, and porosity were extracted. Results: A total of 24 articles were included for full-text review and data extraction. There was only one experimental study comparing collagen I (natural hydrogel) and polyethylene glycol (PEG) in an in vitro setting. The included study suggested the behavior of cells with PEG is more expectable in the injury site, which makes it a more reliable scaffold for neurites. Conclusions: There is limited research comparing and evaluating both types of natural and self-assembling peptides (SAPs) in the same animal or in vitro study, despite its importance. Although we assume that the remodeling of natural scaffolds may lead to a stable hydrogel, there was not a definitive conclusion that synthetic hydrogels are more beneficial than natural hydrogels in neuronal regeneration.

In Vitro Nonlinear Viscoelastic Characterization of the Porcine Spinal Cord

2013 ◽  
Author(s):  
Snehal S. Shetye ◽  
Kevin L. Troyer ◽  
Femke Streijger ◽  
Jae Lee ◽  
Brian K. Kwon ◽  
...  
Keyword(s):  
United States ◽  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Financial Burden ◽  
Mechanical Damage ◽  
The United States ◽  
Dynamic Events ◽  
Nonlinear Viscoelastic ◽  
Static Mechanical

Approximately 12,400 new cases of spinal cord injuries (SCI) are reported in the United States every year. It has been estimated that the annual financial burden of SCI in the United States is approximately $7.736 billion. The mechanisms of mechanical damage to the spinal cord can be broadly classified into distraction, dislocation or contusion. Distraction injuries are predominantly caused by rapid acceleration-deceleration of the cervical spine. Vertebral burst fractures commonly result in contusion of the spinal cord and relative dislocation of adjacent vertebrae can inter-segmentally shear the spinal cord resulting in injury. Multiple studies have examined the quasi-static mechanical properties of the spinal cord [1–3]. However, considering that most spinal cord injuries occur during dynamic events with relatively high strain rates (ex: 10/s), alarmingly few studies have investigated the time-dependent mechanical characteristics of the spinal cord.

A Compressible, Transversely Isotropic, Hyperelastic Constitutive Model of the Guinea Pig Spinal Cord White Matter

2007 ◽  
Author(s):  
Beth Galle ◽  
Hui Ouyang ◽  
Riyi Shi ◽  
Eric A. Nauman
Keyword(s):  
Spinal Cord ◽  
White Matter ◽  
Guinea Pig ◽  
Constitutive Model ◽  
Spinal Cord Injuries ◽  
Transversely Isotropic ◽  
Element Model ◽  
Plane Shear ◽  
Tissue Compression

Slow compression spinal cord injuries occur when the spinal canal narrows, the consequence of degenerative, infective, or oncologic legion growth, and exerts pressure throughout the spinal cord. Transverse tissue compression results in an amalgamation of mechanical insults at the cellular level [1]. However, the mechanism of cellular injury has yet to be elucidated. We have recently developed a hyperelastic, isotropic plane strain finite element model (FEM) of the guinea pig spinal cord white matter response to transverse compression based on force-deformation curves measured in vitro. The strongest correlation with in vitro axonal injury density was the combination of the in-plane shear stress with the in- and out-of-plane normal stresses quantified using the FEM [2]. However, we hypothesize that the guinea pig spinal cord white matter is a transversely isotropic material. Material anisotropy must be incorporated into the FEM to achieve enhanced model accuracy, specifically, the prediction of axial stresses within the spinal cord parenchyma during transverse tissue compression. Therefore, the objective of the present study was to propose a compressible, transversely isotropic, hyperelastic constitutive model of the guinea pig spinal cord white matter.

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