Fischell Department of Bioengineering Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/6628
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Item ENHANCING BIOPRINTING STRATEGIES TOWARDS THE DEVELOPMENT OF BIOMIMETIC OSTEOCHONDRAL TISSUE ENGINEERING SCAFFOLDS(2023) Choe, Robert; Fisher, John P; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Osteoarthritis is a highly prevalent rheumatic musculoskeletal disorder that affects approximately 900,000 Americans annually and is characterized by the progressive breakdown of the articular cartilage and remodeling of the subchondral bone in the synovial joint. During early-stage osteoarthritis, the articular cartilage begins to degrade, the synovial joint space narrows, and the subchondral bone undergoes rapid bone turnover, leading to insufficient bone mineralization and compromised matrix integrity. While decades of research have revealed that an intricate balance between the bone and cartilage layers influences biochemical and biomechanical changes experienced within the osteochondral unit, most osteochondral tissue engineering scaffolds have not achieved clinical viability. Tissue engineering (TE) strategies, such as 3D bioprinting (3DP), offer a new avenue to help develop novel osteochondral tissue engineering scaffolds to regenerate healthy and diseased osteochondral joints. In this project, our immediate goal is to expand the repertoire of osteochondral bioprinting strategies toward developing a biomimetic, 3D-printed osteochondral scaffold that can be implanted into acute focal cartilage defects during early-stage OA. We will explore the designs and fabrication strategies of various 3D-printed biomimetic osteochondral interface scaffolds with enhanced mechanics guided by computational simulations. Additionally, we will examine the potential of utilizing osteoblast- and osteoclast-lineage cell co-cultures to improve regenerative outcomes at the bone scaffold layer of osteochondral tissue engineering scaffolds. The long-term goal of this work is to aid in developing a biomimetic 3D printed osteochondral scaffold that has enhanced load-bearing properties and elevated regeneration potential to recreate the unique osteochondral architecture at each distinct tissue layer.Item INSTRUMENTATION AND AUTOMATION FOR STIMULATED BRILLOUIN SPECTROSCOPY(2023) Frank, Eric; Scarcelli, Giuliano; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The use of Brillouin spectroscopy for noninvasive probing of the mechanical properties of biologically relevant materials shows great promise. Stimulated Brillouin scattering (SBS) spectroscopy has the potential to significantly improve measurement speed and resolution by amplifying the scattered signal resonantly. However, current SBS spectrometers have been limited by fundamental and practical constraints in detection parameters. Here, we develop and demonstrate a novel LabVIEW-automated SBS instrumentation scheme in which a number of instruments that otherwise operate independently are automatized and synchronized from a singular LabVIEW program with emphasis on the user interface. Additionally, localization theory, originating from fluorescence-based super resolution microscopy techniques, is applied to the acquisition of SBS spectra, and experimentally demonstrated using this instrumentation scheme, resulting in spectra being acquired an order of magnitude faster while maintaining performances in terms of signal to noise ratio (SNR) and measurement precision.Item Quantitative Motion Analysis of the Upper Limb: Establishment of Normative Kinematic Datasets and Systematic Comparison of Motion Analysis Systems(2022) Wang, Sophie Linyi; Kontson, Kimberly L; White, Ian; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Upper limb prosthetic devices with advanced capabilities are currently in development. With these advancements brings to light the importance of objectively and quantitatively measuring effectiveness and benefit of these devices. Recently, the application of motion capture (i.e., digital tracking of upper body movements in space) to performance-based outcome measures has gained traction as a possible tool for human movement assessment that could facilitate optimal device selection, track rehabilitative progress, and inform device regulation and review. While motion capture shows promise, the clinical, regulatory, and industry communities would benefit from access to large clinical and normative datasets from different motion capture systems and a better understanding of advantages and limitations of different motion capture approaches. The first objective of this dissertation is to establish kinematic datasets of normative and upper-limb prosthesis user motion. The normative kinematic distributions of many performance-based outcome measures are not established, and it is difficult to determine departures from normative patterns without relevant clinical expertise. In Specific Aim 1, normative and clinically relevant datasets were created using a gold standard motion capture system to record participants performing standardized tasks from outcome measures. Without kinematic data, it is also difficult to identify informative kinematic features and tasks that exhibit characteristic differences from normative motion. The second objective is to identify salient kinematic characteristics associated with departures from normative motion. In Specific Aim 2, an unsupervised K-means machine learning algorithm was applied to the previously collected data to determine motions and tasks that distinguish between normative and prosthesis user movement. The third objective is to compare three commonly used motion capture systems that vary in motion tracking mechanisms. The most informative tasks and kinematic characteristics previously identified will be used to evaluate the detection of these differences for several motion capture systems with varying tracking methods in Specific Aim 3.Item Brillouin confocal microscopy in off-axis configuration(2021) Fiore, Antonio; Scarcelli, Giuliano; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Three-dimensional Brillouin confocal microscopy is an imaging modality that correlates with mechanical properties in biological media from subcellular to tissue level. Over the years we developed new approaches to this technique that improve the spectral performance and can measure directly the local refractive index as well as the complex modulus of the sample; to achieve this goal, we probed two co-localized Brillouin scattering geometries. The confocal microscopy setting ensures three-dimensional mapping with high resolution, while the back scattering configuration allows access to the sample from the same side. For these reasons, such an instrument constitutes a new approach in investigating biological phenomena providing both local index of refraction and mechanical information with a single measurement. This technique has been improved in speed and spatial resolution in order to be applied to some specific challenging material characterization such as liquid-liquid phase separation.Item Three-Dimensional Characterization and Modulation of Corneal Biomechanics via Brillouin Microscopy(2021) Webb, Joshua Norman; Scarcelli, Giuiano; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Corneal mechanical properties are needed for diagnosing and monitoring the progression of ocular disorders such as keratoconus, screening for refractive surgeries, and evaluating treatment procedures including corneal cross-linking. Alterations of these mechanical properties are often localized to a specific area within the cornea. However, there exists a clinical gap of measuring local mechanical properties as current methods are contact-based and provide global measurements. The goal of this dissertation is to close this gap by establishing a three-dimensional, noninvasive characterization method of corneal biomechanics. Previously, our laboratory developed Brillouin microscopy as an imaging modality which can noninvasively extract mechanical measurements of a material. Here, using Brillouin microscopy, we characterized the stiffening effects of accelerated and localized cross-linking procedures with three-dimensional resolution. However, existing procedures to extract elastic modulus information from Brillouin measurements rely on empirical calibrations because a fundamental understanding between the two had not yet been established. In practice, this limits Brillouin measurements to relative softening / stiffening information, which, while useful to compare protocol efficacies, are not optimal for modeling long-term shape behavior of the cornea in clinical settings. Here, we address this shortcoming of Brillouin microscopy. First, we identified that both Brillouin-derived mechanical modulus and traditional elastic modulus are dependent on two major biophysical factors: hydration and the mechanical properties of the solid matrix. We derived and experimentally verified a quantitative relationship to describe the distinct moduli dependencies of such factors. Based on these relationships, we derived a procedure to extract the elastic modulus of the cornea from experimental measurements of Brillouin frequency shift and hydration, two clinically available parameters. Thus, the work presented here establishes a spatially resolved, noninvasive method for measuring corneal elastic modulus.Item FAILURE MECHANISMS OF PEDIATRIC GROWING ROD CONSTRUCTS(2017) Hill, Genevieve A-L.; Fisher, John P; Dreher, Maureen L; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Early onset scoliosis (EOS) affects a vulnerable population of young children, and occurs at critical ages when the spine and thorax are developing. Children suffering with EOS have higher mortality rates due to cardiopulmonary complications; therefore, treatment for these patients can be life-saving. Pediatric growing rod constructs are an important treatment option for young patients with severe and progressive spinal deformities because they encourage growth and correction of the spinal curvature through successive lengthening procedures. However, growing rod constructs suffer from complication rates as high as 72%, which often lead to unplanned reoperations. To help prevent future failures of the same root cause, the failure mode and mechanism must be identified, which tell us how and why the devices failed respectively. This research included the first study to examine multiple, retrieved pediatric growing rod constructs from various sites to systematically investigate these significant items. The retrieval study revealed that rod fracture (failure mode) was due to bending fatigue (failure mechanism), and stress concentrations play an important role in rod fractures. The information obtained from the retrieval study enhanced the understanding of in vivo loading conditions experienced by the device and established clinically-relevant parameters for a mechanical bench model. This research also included the development and validation of a novel mechanical bench model that successfully replicated rod fracture due to bending fatigue. A mechanical bench model that is predicated on clinical outcomes can serve as a tool for engineers and researchers who are looking to improve pediatric growing rod constructs as it will enable them to make relevant predictions about the device’s resistance to failure. For example, the model was used in this research to investigate how the unique characteristics of pediatric growing rod constructs such as construct configuration and lengthening affect mechanical performance of the device. Key recommendations regarding surgical technique were identified in the retrieval study and verified through bench testing. The data obtained during this research can ultimately be used to reduce failure rates and unplanned revisions in this patient population.Item Effects of Load History on Ovine Spinal Range of Motion(2016) Rotunno, Giuliana; Hsieh, Adam H; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Loading of spinal motion segment units alters biomechanical properties by modifying flexibility and range of motion. This study utilizes angular displacement due to an applied bending moment to assess biomechanical function during high-magnitude and prolonged compressive loading of ovine lumbar motion segments. High compressive loads, representative of physiological lifestyle and occupational behaviors, appear to limit fluid recovery of the intervertebral disc, thereby modifying spinal flexibility and increasing spinal instability. Intermittent extensions, or backwards bending movements, may provide a protective effect against the load-induced spinal instability. This study contributes a greater understanding of the effects of load history on the function and health of the lumbar spine. Findings may inform future efforts investigating adjustments in spinal posture to preserve or promote the recovery of lumbar spinal biomechanics.Item UTILIZATION OF PNEUMATIC ARTIFICIAL MUSCLES TO STUDY EFFECTS OF LOAD HISTORY ON THE INTERVERTEBRAL DISC(2015) Russell, Joseph; Hsieh, Adam H; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Degenerative disc disease is commonly linked with low back pain, a major musculoskeletal disorder contributing to an annual socioeconomic impact of over $100 billion. The intervertebral disc (IVD) plays a critical role in spinal load bearing and many of the mechanisms of its degeneration are still unknown. This study focused on eliciting gene expression changes of the Nucleus Pulposus (NP), the inner region of the IVD critical to load support using an in vivo rat model. First, pneumatic artificial muscles (PAMs) were calibrated and integrated into a small loading device as an actuation mechanism. Next, various load histories were then applied on IVDs and gene expression was determined by qRT-PCR. Results show that discs with increased intradiscal pressure led increased expression of genes common to the NP. This study contributes to the better understanding of how load history alters IVD health and validates a device for future long term studies.Item Effect of Load History on Ovine Intervertebral Disc Biomechanics(2014) Goodley, Addison; Hsieh, Adam H; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Loading of the intervertebral disc (IVD) alters biomechanical properties by modifying fluid distribution in the nucleus pulposus -changing hydrostatic pressure and tissue response- during force transmission along the spine. This study combines pressure, vertical displacement, and radial bulge measurements to assess biomechanical function during healthy and adverse loading of ovine lumbar motion segments. High compressive loads and simultaneous transient exertions, representative of obesity or other high-load lifestyles, are expected to limit fluid recovery and inhibit IVD biomechanical function compared to low compressive load controls with similar transient exertions. Specifically, the adverse group will (1) lose the ability to generate intradiscal pressures equivalent to control discs at equal loads and (2) exhibit a greater degree of deformation and bulge during comparable loading. This study contributes a greater understanding of the effects of load on IVD health. Findings may inform future efforts to preserve disc biomechanics and reverse IVD loss of function.Item Physical properties of lamprey spinal cord regeneration: adaptive vs. maladaptive recovery(2014) Luna Lopez, Carlos; Aranda-Espinoza, Helim J.; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Spinal cord injury (SCI) is a physical trauma that can result in paralysis and even death; to date no treatment exists that can successfully promote functional or adaptive recovery. Although humans are unable to regenerate after complete SCI, there are animal models that have been studied for their ability to regrow and reconnect their nerve fibers. From the group of animals that are capable of spinal cord regeneration, in the best studied is the lamprey (Petromyzon Marinus) it has been noted that recovery can be maladaptive. When left to recover at warm temperature (23 ⁰C) most lampreys had adaptive behavior, but at cold temperature (10 ⁰C) most lampreys showed maladaptive behavior. In this thesis we studied the physical factors that influence adaptive and maladaptive recovery in lampreys. In the first part, we analyzed axonal regeneration and blood clot formation at early time points after injury (1-2 weeks). We found that lampreys in cold temperature have a blood clot that could be blocking spinal cord regeneration. In the second part of this work, we analyzed the biomechanical and structural differences between lampreys in warm and cold temperature. We used in vivo X-ray imaging and tensile loading testing of the spinal cord and notochord structures, before and after injury. We found that lampreys at warm temperature are more favorable to create a permissive mechanical and structural environment for regeneration. Lastly, we used those lessons learned previously to enhance regeneration of maladaptive animals. We removed the blood clot at the injury site and created a time frequency analysis to measure the recovery of coordination. We found that lampreys in cold temperature with clot removal had a more adaptive recovery after injury than those without removal. In summary, by using the lamprey we were able to compare the differences between regeneration in warm and cold temperature and found the physical factors that influence maladaptive recovery. Removing one of these factors, in this case the blood clot, successfully enhanced the recovery of coordination. These results have the potential to be translated to higher animals and aid in the creation of successful treatments for SCI.