Ryan Gilbert

Ryan Gilbert
Rensselaer Polytechnic Institute | RPI · Department of Biomedical Engineering

PhD

About

97
Publications
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2,791
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Publications

Publications (97)
Article
Nerve guidance scaffolds containing anisotropic architectures provide topographical cues to direct regenerating axons through an injury site to reconnect the proximal and distal end of an injured nerve or spinal cord. Previous in vitro cultures of individual neurons revealed that fiber characteristics such as fiber diameter and inter-fiber spacing...
Article
Electrospun fibers are versatile biomaterial platforms with great potential to support regeneration. Electrospun fiber characteristics such as fiber diameter, degree of alignment, rate of degradation, and surface chemistry enable the creation of unique, tunable scaffolds for various drug or gene delivery applications. The delivery of genetic materi...
Article
Neurological and functional recovery is limited following central nervous system injury and severe injury to the peripheral nervous system. Extracellular matrix (ECM)-mimetic hydrogels are of particular interest as regenerative scaffolds for the injured nervous system as they provide 3D bioactive interfaces that modulate cellular response to the in...
Article
Magnetic fiber composites combining superparamagnetic iron oxide nanoparticles (SPIONs) and electrospun fibers have shown promise in tissue engineering fields. Controlled grafting of SPIONs to the fibers post-electrospinning generates biocompatible magnetic composites without altering desired fiber morphology. Here, for the first time, we assess th...
Article
17β-Estradiol (E2) confers neuroprotection in preclinical models of spinal cord injury when administered systemically. The goal of this study was to apply E2 locally to the injured spinal cord for a sustained duration using poly(pro-E2) film biomaterials. Following contusive spinal cord injury in adult male mice, poly(pro-E2) films were implanted s...
Article
Full-text available
Electrospinning is a fabrication technique used to produce nano- or micro- diameter fibers to generate biocompatible, biodegradable scaffolds for tissue engineering applications. Electrospun fiber scaffolds are advantageous for neural regeneration because they mimic the structure of the nervous system extracellular matrix and provide contact guidan...
Article
Full-text available
Astrocytes are responsible for a wide variety of essential functions throughout the central nervous system. The protein markers glial fibrillary acidic protein (GFAP), glutamate aspartate transporter (GLAST), glutamate transporter‐1 (GLT‐1), glutamine synthetase (GS), 10‐formyltetrahydrofolate dehydrogenase (ALDH1L1), and the transcription factor S...
Article
Following spinal cord injury, astrocytes at the site of injury become reactive and exhibit a neurotoxic (A1) phenotype, which leads to neuronal death. In addition, the glial scar, which is composed of reactive astrocytes, acts as a chemical and physical barrier to subsequent axonal regeneration. Biomaterials, specifically electrospun fibers, induce...
Article
Full-text available
Researchers are investigating the use of biomaterials with aligned guidance cues, like those provided by aligned electrospun fibers, to facilitate axonal growth across critical-length peripheral nerve defects. To enhance the regenerative outcomes further, these aligned fibers can be designed to provide local, sustained release of therapeutics. The...
Article
Astrocytes are dynamic cells residing in the central nervous system exhibiting many diverse functions. Astrocytes quickly change and present unique phenotypes in response to injury or disease. Here, we briefly summarize recent information regarding astrocyte morphology and function and provide brief insight into their phenotypic changes following i...
Article
Electrospun poly-L-lactic acid (PLLA) fibers are commonly used for tissue engineering applications due to their uniform morphology, and their efficacy can be further enhanced via surface modification. In this study, we aimed to increase neurite outgrowth along electrospun fibers by coating with silk fibroin (SF), a bio-inert protein derived from Bo...
Article
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Macrophages are a heterogeneous and plastic population of cells whose phenotype changes in response to their environment. Macrophage biologists utilize peritoneal (pMAC) and bone marrow-derived macrophages (BMDM) for in vitro studies. Given that pMACs mature in vivo while BMDM are ex vivo differentiated from stem cells, it is likely that their resp...
Article
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Central nervous system (CNS) injuries persist for years, and currently there are no therapeutics that can address the complex injury cascade that develops over this time-scale. 17β-estradiol (E2) has broad tropism within the CNS, targeting and inducing beneficial phenotypic changes in myriad cells following injury. To address the unmet need for vas...
Article
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Nervous system damage caused by physical trauma or degenerative diseases can result in loss of sensory and motor function for patients. Biomaterial interventions have shown promise in animal studies, providing contact guidance for extending neurites or sustained release of various drugs and growth factors; however, these approaches often target onl...
Article
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The hydrophobicity of electrospun poly-L-lactic acid (PLLA) fibers hinders their integration with surrounding tissue for a variety of applications. In this study, we increased PLLA fiber hydrophilicity by incorporating the natural surfactant, lactonic sophorolipid (LSL). PLLA+LSL fibers had similar fiber morphology but significantly greater surface...
Article
Gene therapy is a promising form of treatment for those suffering from neurological disorders or central nervous system (CNS) injury, however, obstacles remain that limit its translational potential. The CNS is protected by the blood brain barrier, and this barrier blocks genes from traversing into the CNS if administered outside of the CNS. Viral a...
Article
Macrophages are immune cells involved in wound healing and tissue regeneration; however, the sustained presence of pro-inflammatory macrophages in wound sites impairs healing. In this study, we shifted peritoneal macrophage polarization away from a pro-inflammatory (M1) phenotype through exposure to stabilized interleukin-4 (IL-4) in poly(lactic-co...
Article
Composites combining superparamagnetic iron oxide nanoparticles (SPIONs) and polymers are largely present in modern (bio)materials. However, while SPIONs embedded in polymer matrices are classically reported, the mechanical and degradation properties of the polymer scaffold are impacted by the SPIONs. Therefore, the controlled anchoring of SPIONs o...
Article
Full-text available
Three aligned, electrospun fiber scaffolds with unique surface features were created from poly-L-lactic acid (PLLA). Fibers without surface nanotopography (smooth fibers), fibers with surface divots (shallow pits), and fibers with surface pits (deeper pits) were fabricated, and fiber alignment, diameter, and density were characterized using scannin...
Article
Over several decades, biomaterial scientists have developed materials to spur axonal regeneration and limit secondary injury and tested these materials within preclinical animal models. Rarely, though, are astrocytes examined comprehensively when biomaterials are placed into the injury site. Astrocytes support neuronal function in the central nervo...
Article
Magnetic electrospun fibers are of interest to biomaterial applications that strive to provide cell guidance that can be delivered using minimally invasive techniques. Magnetic electrospun fibers can be injected then magnetically positioned in situ, and the aligned fiber scaffolds provide consistent topographical guidance to cells. We developed and...
Article
The topography of electrospun fiber scaffolds modifies astrocytes toward in vivo-like morphologies and behaviors. However, little is known about how electrospun fiber diameter influences astrocyte behavior. In this work, aligned fibers with two distinct nanoscale fiber diameters (808nm and 386nm) were prepared and the astrocyte response was measure...
Article
Full-text available
Aligned, electrospun fiber scaffolds provide topographical guidance for regenerating neurons and glia after central nervous system injury. To date, no study has explored how fiber surface nanotopography affects astrocyte response to fibrous scaffolds. Astrocytes play important roles in the glial scar, the blood brain barrier, and in maintaining hom...
Article
Full-text available
Electrospinning is a robust material fabrication method allowing for fine control of mechanical, chemical, and functional properties in scaffold manufacturing. Electrospun fiber scaffolds have gained prominence for their potential in a variety of applications such as tissue engineering and textile manufacturing, yet none have assessed the impact of...
Article
Electrospun poly-L-lactic acid (PLLA) fiber scaffolds are used to direct axonal extension in neural engineering models. We aimed to improve the efficacy of these fibers in promoting neurite outgrowth by altering surface topography and reducing fiber elastic modulus through the incorporation of a compatibilized blend, poly-L-lactic acid-poly(pentade...
Chapter
Electrospun fibers are commonly used for tissue engineering purposes. The topography of nano- and microfibrous scaffolds enables cells to attach and migrate by providing a network that is similar to the extracellular matrix (ECM). The use of aligned electrospun fiber scaffolds is particularly relevant in spinal cord injury (SCI), where directed uni...
Article
Electrodes implanted in the brain or spinal cord trigger the activation of resident astrocytes. In their reactive state, astrocytes surrounding the electrode form a glial scar, compromising the ability of the electrode to interface with the surrounding neural tissue. One approach to reduce the inhibiting scar tissue is to incorporate nanoarchitectu...
Article
Full-text available
Affecting approximately 17,000 new people each year, spinal cord injury (SCI) is a devastating injury that leads to permanent paraplegia or tetraplegia. Current pharmacological approaches are limited in their ability to ameliorate this injury pathophysiology, as many are not delivered locally, for a sustained duration, or at the correct injury time...
Article
Currently, it is unknown how the mechanical properties of electrospun fibers, and the presentation of surface nanotopography influence macrophage gene expression and protein production. By further elucidating how specific fiber properties (mechanical properties or surface properties) alter macrophage behavior, it may be possible to create electrosp...
Article
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Electrospun fiber scaffolds crafted from polyesters are studied extensively for potential tissue engineering applications. For translation of electrospun fibers into the clinic, the FDA requires analysis and quantification of any organic solvent that may be retained in the fibers since many organic solvents can negatively affect cells and tissues....
Article
Peritoneal macrophages (PMACs) and spinal cord astrocytes were exposed to varying concentrations of soluble sophorolipid butyl ester diacetate (SLBEDA) in vitro. Macrophages and astrocytes demonstrated no decrease in viability in response to SLBEDA. Studying pro- and anti-inflammatory genes, PMACs did not show a shift towards a pro-inflammatory phe...
Article
There is currently no cure for individuals with spinal cord injury (SCI). While many promising approaches are being tested in clinical trials, the complexity of SCI limits several of these approaches from aiding complete functional recovery. Several different categories of biomaterials are investigated for their ability to guide axonal regeneration...
Article
Nanoparticles are increasingly being studied within experimental models of spinal cord injury (SCI). They are used to image cells and tissue, move cells to specific regions of the spinal cord, and deliver therapeutic agents locally. The focus of this article is to provide a brief overview of the different types of nanoparticles being studied for sp...
Article
Statement of significance: Novel biomedical devices delivering electrical stimulation are being developed to mitigate symptoms of Parkinson's, treat drug-resistant depression, control movement or enhance verve regeneration. Carbon nanotubes and other novel materials are being explored for novel nano-neuro devices based on their unique properties....
Article
Benzoxaboroles are a family of organoboron molecules, which have been finding over the past few years an increasing number of biological applications, notably for the design of new drugs. Given that these molecules are still relatively new in the biomedical context, very few investigations regarding their formulation have been reported to date. Her...
Article
Benzoxaboroles are a family of organoboron molecules, which have been finding over the past few years an increasing number of biological applications, notably for the design of new drugs. Given that these molecules are still relatively new in the biomedical context, very few investigations regarding their formulation have been reported to date. Her...
Article
Full-text available
Electrospinning is the process by which a scaffold containing micrometer and nanometer diameter fibers are drawn from a polymer solution or melt using a large voltage gradient between a polymer emitting source and a grounded collector. Ramakrishna and colleagues first investigated electrospun fibers for neural applications in 2004. Following this i...
Article
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The surface of aligned, electrospun poly-L-lactic acid (PLLA) fibers was chemically modified to determine if surface chemistry and hydrophilicity could improve neurite extension from chick dorsal root ganglia. Specifically, diethylenetriamine (DTA, for amine functionalization), 2-(2-aminoethoxy)ethanol (AEO, for alcohol functionalization), or GRGDS...
Article
Full-text available
Nerve growth factor releasing composite nanoparticles (NGF-cNPs) were developed to direct the extension of neurite outgrowth from dorsal root ganglia (DRG). Iron oxide magnetic nanoparticles were incorporated into poly-L-lactic acid (PLLA) nanoparticles in order to position the NGF-cNPs in a culture dish. Neurites growing from DRG extended towards...
Article
The Astrocytes are one of the most important and abundant resident glial cells of the central nervous system (CNS). They play a critical role in the foreign body response, by participating in the formation of the glial scar sunouncling implants. As part of the effort to minimize the foreign body response, biomaterials strategies einployiug engineer...
Article
We hypothesized that fiber diameter within an electrospun fiber scaffold would affect astrocyte elongation and maturation. To examine the relationship, astrocytes were seeded on 400nm and 800nm diameter electrospun PLLA fibers. Immunohistochemistry was used to monitor cell morphology, and GLT-1 expression over the first 96 hours after seeding. The...
Article
In an attempt to increase the rate of neurite extension from E9 chick embryo dorsal root ganglion (DRG) on electrospun fiber scaffolds we experimented with two drugs that have been used previously to affect neuronal growth. Blebbistatin and paclitaxel were added to DRG cultured on electrospun fibers in an attempt to increase the rate of neurite ext...
Article
Full-text available
Integrin-mediated cell adhesion to the ECM regulates many physiological processes in part by controlling cell proliferation. It is well established that many normal cells require integrin-mediated adhesion to enter S phase of the cell cycle. Recent evidence indicates that integrins also regulate cytokinesis. Mechanical properties of the ECM can dic...
Article
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Tissue engineering scaffolds are often designed without appropriate consideration for the translational potential of the material. Solid scaffolds implanted into central nervous system (CNS) tissue to promote regeneration may require tissue resection to accommodate implantation. Or alternatively, the solid scaffold may be cut or shaped to better fi...
Article
Full-text available
Following central nervous system (CNS) injury, activated astrocytes form glial scars, which inhibit axonal regeneration, leading to long-term functional deficits. Engineered nanoscale scaffolds guide cell growth and enhance regeneration within models of spinal cord injury. However, the effects of micro-/nanosize scaffolds on astrocyte function are...
Chapter
Full-text available
Electrospun poly-L-lactic acid (PLLA) fibers are presently explored as tissue engineering platforms for regeneration of the central nervous system. In particular, aligned, electrospun fibers are capable of directing astrocyte cellular extension and migration. The precise mechanisms by which aligned, electrospun substrates alter glial cell behavior...
Article
The stromal tissue surrounding most carcinomas is comprised of an extracellular matrix densely packed with collagen-I fibers, which are often highly aligned in metastatic disease. Here we developed an in vitro model to test the effect of an aligned fibrous environment on cancer cell morphology and behavior, independent of collagen ligand presentati...
Article
Superparamagnetic iron oxide nanoparticles (SPIONs) can generate heat when subjected to an alternating magnetic field (AMF). In the European Union, SPIONs actuated by AMF are used in hyperthermia treatment of glioblastoma multiforme, an aggressive form of brain cancer. Current data from clinical trials suggest that this therapy improves patient lif...
Article
Hydrogels are studied extensively for many tissue engineering applications, and their mechanical properties influence both cellular and tissue compatibility. However, it is difficult to compare the mechanical properties of hydrogels between studies due to a lack of continuity between rheological protocols. This study outlines a straightforward prot...
Article
Full-text available
Objective: Both electrical stimuli (endogenous and exogenous) and topographical cues are instructive to axonal extension. This report, for the first time, investigated the relative dominance of directional topographical guidance cues and directional electrical cues to enhance and/or direct primary neurite extension. We hypothesized the combination...
Article
Full-text available
Purpose: Superparamagnetic iron oxide nanoparticles are currently approved for use as an adjunctive treatment to glioblastoma multiforme radiotherapy. Radio frequency stimulation of the nanoparticles generates localised hyperthermia, which sensitises the tumour to the effects of radiotherapy. Clinical trials reported thus far are promising, with a...
Article
Immediately following spinal cord injury, further injury can occur through several secondary injury cascades. As a consequence of cell lysis, an increase in extracellular Ca(2+) results in additional neuronal loss by inducing apoptosis. Thus, hydrogels that reduce extracellular Ca(2+) concentration may reduce secondary injury severity. The goal of...
Conference Paper
Introduction: Electrospun fibers are often generated using synthetic, hydrophobic polymers dissolved in an organic solvent. It is generally assumed that the solvent is evaporated before the fibers are used in cellular studies by placing the fibers under vacuum or in a desiccator, but whether solvent has been removed has never been verified. 1 In th...
Article
In this study, we created a new method of electrospinning capable of controlling the surface structure of individual fibers (fiber nanotopography). The nanotopographical features were created by a phase separation in the fibers as they formed. To control the phase separation, a non-solvent (a chemical insoluble with the polymer) was added to an ele...
Article
Following spinal cord injury, changes in glial cell behavior and the local extracellular environment combine to produce an inhibitory environment for neuronal regeneration. Hydrogel biomaterials are ideal for treating spinal cord injury as many are injectable and conform to irregular lesion geometries. Numerous studies present novel hydrogel system...
Article
It has become increasingly clear that the cellular microenvironment, in particular the extracellular matrix, plays an important role in regulating cell function. However, the extracellular matrix is extraordinarily complex in both its makeup and its physical properties. Therefore, there is a need to develop model systems to independently evaluate t...
Article
Full-text available
Recent evidence demonstrates the ability to change cell function by altering the physical properties of electrospun scaffolds, but many studies still do not characterize electrospun fiber alignment and diameter. To aid in the reporting of these crucial properties, we demonstrate two methods of quantifying electrospun fiber alignment with one method...
Article
Full-text available
The use hydrogels for bone regeneration has been limited due to their inherent low modulus to support cell adhesion and proliferation as well as their susceptibility to bacterial infections at the wound site. To overcome these limitations, we evaluated multifunctional polysaccharide hydrogels of varying stiffness in order to obtain the optimum stif...
Chapter
Carbon nanotubes have remained at the center of nanotechnology research for the past two decades, and have been increasingly present in the areas of biology and biotechnology. While questions still remain about the toxicity of these materials, there is great interest in exploiting their unique properties to create innovative biotechnology applicati...
Article
Abstract Lymphatic dysfunction in lymphedema results in chronic accumulation of interstitial fluid and life-long tissue swelling. In the absence of restored lymphatic drainage via adequate lymphangiogenesis, the interstitial environment can remodel in ways that decrease the elevated interstitial stress. Presently, relatively little is known about t...
Conference Paper
We describe the patterning of neuronal cultures by a laser-based printing system. Embryonic chick cortical neurons were transferred into predetermined array positions with micron accuracy, enabling detailed study of neuronal migration, aggregation, and neurite outgrowth regulated by cell-cell interactions on a homogeneous surface. Images of cells w...