Matching Items (22)
Filtering by
- All Subjects: Drug Delivery
- All Subjects: Biomaterials
- Creators: Harrington Bioengineering Program
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
- Member of: Theses and Dissertations
- Status: Published
Description
Traumatic brain injury (TBI) may result in numerous pathologies that cannot currently be mitigated by clinical interventions. Stem cell therapies are widely researched to address TBI-related pathologies with limited success in pre-clinical models due to limitations in transplant survival rates. To address this issue, the use of tissue engineered scaffolds as a delivery mechanism has been explored to improve survival and engraftment rates. Previous work with hyaluronic acid \u2014 laminin (HA-Lm) gels found high viability and engraftment rates of mouse fetal derived neural progenitor/stem cells (NPSCs) cultured on the gel. Furthermore, NPSCs exposed to the HA-Lm gels exhibit increased expression of CXCR4, a critical surface receptor that promotes cell migration. We hypothesized that culturing hNPCs on the HA-Lm gel would increase CXCR4 expression, and thus enhance their ability to migrate into sites of tissue damage. In order to test this hypothesis, we designed gel scaffolds with mechanical properties that were optimized to match that of the natural extracellular matrix. A live/dead assay showed that hNPCs preferred the gel with this optimized formulation, compared to a stiffer gel that was used in the CXCR4 expression experiment. We found that there may be increased CXCR4 expression of hNPCs plated on the HA-Lm gel after 24 hours, indicating that HA-Lm gels may provide a valuable scaffold to support viability and migration of hNPCs to the injury site. Future studies aimed at verifying increased CXCR4 expression of hNPCs cultured on HA-Lm gels are necessary to determine if HA-Lm gels can provide a beneficial scaffold for stem cell engraftment therapy for treating TBI.
ContributorsHemphill, Kathryn Elizabeth (Author) / Stabenfeldt, Sarah (Thesis director) / Brafman, David (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Cardiac tissue engineering is an emerging field that has the potential to regenerate and repair damaged cardiac tissues after myocardial infarction. Numerous studies have introduced hydrogel-based cardiac tissue constructs featuring suitable microenvironments for cell growth along with precise surface topographies for directed cell organization. Despite significant progress, previously developed cardiac tissue constructs have suffered from electrically insulated matrices and low cell retention. To address these drawbacks, we fabricated micropatterned hybrid hydrogel constructs (uniaxial microgrooves with 50 µm with) using a photocrosslinkable gelatin methacrylate (GelMA) hydrogel incorporated with gold nanorods (GNRs). The electrical impedance results revealed a lower impedance in the GelMA-GNR constructs versus the pure GelMA constructs. Superior electrical conductivity of GelMA-GNR hydrogels (due to incorporation of GNRs) enabled the hybrid tissue constructs to be externally stimulated using a pulse generator. Furthermore, GelMA-GNR tissue hydrogels were tested to investigate the biological characteristics of cultured cardiomyocytes. The F-actin fiber analysis results (area coverage and alignment indices) revealed higher directed (uniaxial) cytoskeleton organization of cardiac cells cultured on the GelMA-GNR hydrogel constructs in comparison to pure GelMA. Considerable increase in the coverage area of cardiac-specific markers (sarcomeric α-actinin and connexin 43) were observed on the GelMA-GNR hybrid constructs compared to pure GelMA hydrogels. Despite substantial dissimilarities in cell organization, both pure GelMA and hybrid GelMA-GNR hydrogel constructs provided a suitable microenvironment for synchronous beating of cardiomyocytes.
ContributorsMoore, Nathan Allen (Author) / Nikkhah, Mehdi (Thesis director) / Smith, Barbara (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and adapt to a plethora of biochemical and biophysical signals from stromal cells and extracellular matrix (ECM) proteins. Due to these complexities, there is a critical need to understand molecular mechanisms underlying cancer metastasis to facilitate the discovery of more effective therapies. In the past few years, the integration of advanced biomaterials and microengineering approaches has initiated the development of innovative platform technologies for cancer research. These technologies enable the creation of biomimetic in vitro models with physiologically relevant (i.e. in vivo-like) characteristics to conduct studies ranging from fundamental cancer biology to high-throughput drug screening. In this review article, we discuss the biological significance of each step of the metastatic cascade and provide a broad overview on recent progress to recapitulate these stages using advanced biomaterials and microengineered technologies. In each section, we will highlight the advantages and shortcomings of each approach and provide our perspectives on future directions.
ContributorsPeela, Nitish (Author) / Nikkhah, Mehdi (Thesis director) / LaBaer, Joshua (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
The primary objective of this research project is to develop dual layered polymeric microparticles with a tunable delayed release profile. Poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) phase separate in a double emulsion process due to differences in hydrophobicity, which allows for the synthesis of double-walled microparticles with a PLA shell surrounding the PLGA core. The microparticles were loaded with bovine serum albumin (BSA) and different volumes of ethanol were added to the PLA shell phase to alter the porosity and release characteristics of the BSA. Different amounts of ethanol varied the total loading percentage of the BSA, the release profile, surface morphology, size distribution, and the localization of the protein within the particles. Scanning electron microscopy images detailed the surface morphology of the different particles. Loading the particles with fluorescently tagged insulin and imaging the particles through confocal microscopy supported the localization of the protein inside the particle. The study suggest that ethanol alters the release characteristics of the loaded BSA encapsulated in the microparticles supporting the use of a polar, protic solvent as a tool for tuning the delayed release profile of biological proteins.
ContributorsFauer, Chase Alexander (Author) / Stabenfeldt, Sarah (Thesis director) / Ankeny, Casey (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
One of the most prominent biological challenges for the field of drug delivery is the blood-brain barrier. This physiological system blocks the entry of or actively removes almost all small molecules into the central nervous system (CNS), including many drugs that could be used to treat diseases in the CNS. Previous studies have shown that activation of the adenosine receptor signaling pathway through the use of agonists has been demonstrated to increase BBB permeability. For example, regadenoson is an adenosine A2A receptor agonist that has been shown to disrupt the BBB and allow for increased drug uptake in the CNS. The goal of this study was to verify this property of regadenoson. We hypothesized that co-administration of regadenoson with a non-brain penetrant macromolecule would facilitate its entry into the central nervous system. To test this hypothesis, healthy mice were administered regadenoson or saline concomitantly with a fluorescent dextran solution. The brain tissue was either homogenized to measure quantity of fluorescent molecule, or cryosectioned for imaging with confocal fluorescence microscopy. These experiments did not identify any significant difference in the amount of fluorescence detected in the brain after regadenoson treatment. These results contradict those of previous studies and highlight potential differences in injection methodology, time windows, and properties of brain impermeant molecules.
ContributorsWohlleb, Gregory Michael (Author) / Sirianni, Rachael (Thesis director) / Stabenfeldt, Sarah (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
With microspheres growing in popularity as viable systems for targeted drug therapeutics, there exist a host of diseases and pathology induced side effects which could be treated with poly(lactic-co-glycolic acid) [PLGA] microparticle systems [6,10,12]. While PLGA systems are already applied in a wide variety the clinical setting [11], microparticles still have some way to go before they are viable systems for drug delivery. One of the main reasons for this is a lack of fabrication processes and systems which produce monodisperse particles while also being feasible for industrialization [10]. This honors thesis investigates various microparticle fabrication techniques \u2014 two using mechanical agitation and one using fluid dynamics \u2014 with the long term goal of incorporating norepinephrine and adenosine into the particles for metabolic stimulatory purposes. It was found that mechanical agitation processes lead to large values for dispersity and the polydispersity index while fluid dynamics methods have the potential to create more uniform and predictable outcomes. The research concludes by needing further investigation into methods and prototype systems involving fluid dynamics methods; however, these systems yield promising results for fabricating monodisperse particles which have the potential to encapsulate a wide variety of therapeutic drugs.
ContributorsRiley, Levi Louis (Author) / Vernon, Brent (Thesis director) / VanAuker, Michael (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
With an increased demand for more enzyme-sensitive, bioresorbable and more biodegradable polymers, various studies of copolymers have been developed. Polymers are widely used in various applications of biomedical engineering such as in tissue engineering, drug delivery and wound healing. Depending on the conditions in which polymers are used, they are modified to accommodate a specific need. For instance, polymers used in drug delivery are more efficient if they are biodegradable. This ensures that the delivery system does not remain in the body after releasing the drug. It is therefore crucial that the polymer used in the drug system possess biodegradable properties. Such modification can be done in different ways including the use of peptides to make copolymers that will degrade in the presence of enzymes. In this work, we studied the effect of a polypeptide GAPGLL on the polymer NIPAAm and compare with the previously studied Poly(NIPAAm-co-GAPGLF). Both copolymers Poly(NIPAAm-co-GAPGLL) were first synthesized from Poly(NIPAAm-co-NASI) through nucleophilic substitution by the two peptides. The synthesis of these copolymers was confirmed by 1H NMR spectra and through cloud point measurement, the corresponding LCST was determined. Both copolymers were degraded by collagenase enzyme at 25 ° C and their 1H NMR spectra confirmed this process. Both copolymers were cleaved by collagenase, leading to an increase in solubility which yielded a higher LCST compared to before enzyme degradation. Future studies will focus on evaluating other peptides and also using other techniques such as Differential Scanning Microcalorimetry (DSC) to better observe the LCST behavior. Moreover, enzyme kinetics studies is also crucial to evaluate how fast the enzyme degrades each of the copolymers.
ContributorsUwiringiyimana, Mahoro Marie Chantal (Author) / Vernon, Brent (Thesis director) / Nikkhah, Mehdi (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Most daily living tasks consist of pairing a series of sequential movements, e.g., reaching to a cup, grabbing the cup, lifting and returning the cup to your mouth. The process by which we control and mediate the smooth progression of these tasks is not well understood. One method which we can use to further evaluate these motions is known as Startle Evoked Movements (SEM). SEM is an established technique to probe the motor learning and planning processes by detecting muscle activation of the sternocleidomastoid muscles of the neck prior to 120ms after a startling stimulus is presented. If activation of these muscles was detected following a stimulus in the 120ms window, the movement is classified as Startle+ whereas if no sternocleidomastoid activation is detected after a stimulus in the allotted time the movement is considered Startle-. For a movement to be considered SEM, the activation of movements for Startle+ trials must be faster than the activation of Startle- trials. The objective of this study was to evaluate the effect that expertise has on sequential movements as well as determining if startle can distinguish when the consolidation of actions, known as chunking, has occurred. We hypothesized that SEM could distinguish words that were solidified or chunked. Specifically, SEM would be present when expert typists were asked to type a common word but not during uncommon letter combinations. The results from this study indicated that the only word that was susceptible to SEM, where Startle+ trials were initiated faster than Startle-, was an uncommon task "HET" while the common words "AND" and "THE" were not. Additionally, the evaluation of the differences between each keystroke for common and uncommon words showed that Startle was unable to distinguish differences in motor chunking between Startle+ and Startle- trials. Explanations into why these results were observed could be related to hand dominance in expert typists. No proper research has been conducted to evaluate the susceptibility of the non-dominant hand's fingers to SEM, and the results of future studies into this as well as the results from this study can impact our understanding of sequential movements.
ContributorsMieth, Justin Richard (Author) / Honeycutt, Claire (Thesis director) / Santello, Marco (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Startle-evoked-movement (SEM), the involuntary release of a planned movement via a startling stimulus, has gained significant attention recently for its ability to probe motor planning as well as enhance movement of the upper extremity following stroke. We recently showed that hand movements are susceptible to SEM. Interestingly, only coordinated movements of the hand (grasp) but not individuated movements of the finger (finger abduction) were susceptible. It was suggested that this resulted from different neural mechanisms involved in each task; however it is possible this was the result of task familiarity. The objective of this study was to evaluate a more familiar individuated finger movement, typing, to determine if this task was susceptible to SEM. We hypothesized that typing movements will be susceptible to SEM in all fingers. These results indicate that individuated movements of the fingers are susceptible to SEM when the task involves a more familiar task, since the electromyogram (EMG) latency is faster in SCM+ trials compared to SCM- trials. However, the middle finger does not show a difference in terms of the keystroke voltage signal, suggesting the middle finger is less susceptible to SEM. Given that SEM is thought to be mediated by the brainstem, specifically the reticulospinal tract, this suggest that the brainstem may play a role in movements of the distal limb when those movements are very familiar, and the independence of each finger might also have a significant on the effect of SEM. Further research includes understanding SEM in fingers in the stroke population. The implications of this research can impact the way upper extremity rehabilitation is delivered.
ContributorsQuezada Valladares, Maria Jose (Author) / Honeycutt, Claire (Thesis director) / Santello, Marco (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Previous research has shown that a loud acoustic stimulus can trigger an individual's prepared movement plan. This movement response is referred to as a startle-evoked movement (SEM). SEM has been observed in the stroke survivor population where results have shown that SEM enhances single joint movements that are usually performed with difficulty. While the presence of SEM in the stroke survivor population advances scientific understanding of movement capabilities following a stroke, published studies using the SEM phenomenon only examined one joint. The ability of SEM to generate multi-jointed movements is understudied and consequently limits SEM as a potential therapy tool. In order to apply SEM as a therapy tool however, the biomechanics of the arm in multi-jointed movement planning and execution must be better understood. Thus, the objective of our study was to evaluate if SEM could elicit multi-joint reaching movements that were accurate in an unrestrained, two-dimensional workspace. Data was collected from ten subjects with no previous neck, arm, or brain injury. Each subject performed a reaching task to five Targets that were equally spaced in a semi-circle to create a two-dimensional workspace. The subject reached to each Target following a sequence of two non-startling acoustic stimuli cues: "Get Ready" and "Go". A loud acoustic stimuli was randomly substituted for the "Go" cue. We hypothesized that SEM is accessible and accurate for unrestricted multi-jointed reaching tasks in a functional workspace and is therefore independent of movement direction. Our results found that SEM is possible in all five Target directions. The probability of evoking SEM and the movement kinematics (i.e. total movement time, linear deviation, average velocity) to each Target are not statistically different. Thus, we conclude that SEM is possible in a functional workspace and is not dependent on where arm stability is maximized. Moreover, coordinated preparation and storage of a multi-jointed movement is indeed possible.
ContributorsOssanna, Meilin Ryan (Author) / Honeycutt, Claire (Thesis director) / Schaefer, Sydney (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12