The purpose of this study is to collect baseline internal and external pressure data for the three most commonly used pelvic circumferential compression devices (PCCD). Unstable pelvic fractures as a result of automobile accidents, falls, and other traumatic injuries mortality rate [3]. Early use of pelvic circumferential compression devices can mitigate fatal outcomes [4]-[5]. Prolonged eternal pressure above 9.3kPa can result in long-term soft tissue damage and pressure ulcers [7]. This study hypothesizes that the application of the three most commonly used PCCDs would result in the same mean maximum point pressure exertion. To study this, internal and external, both analog and digital, pressure apparati were used to collect data. The results of this data collection demonstrate a discrepancy in the pressure distribution between right and left greater trochanters within each PCCD. Additionally, the results suggest there is an effect of internal packing on the pressure exertion externally at the two greater trochanters within each PCCD. Lastly, the differences in pressure exertion between each PCCD, internally and externally, were inconclusive as some compared metrics resulted in statistically significant results while others did not. The methodologies employed in this study can be improved through fixation of pressure collection instruments, utilization of digital pressure mats, and removal of confounding factors. The results of this study indicate that digitized, discrete data over a fixed time interval may be clinically useful, suggesting that a digital data collection would yield more reliable data. Additionally, internally mounted pressure sensor data will provide more precise results than the analog method employed herein, as well as provide insight towards bone reduction and displacement following the application of PCCDs. Finally, the information gathered from this study can be utilized to improve upon existing technologies to create a more innovative solution.

Protein crystallization is a technique for the formation of three-dimensional protein crystals, which is widely utilized by scientists, engineers, and researchers. Protein crystallography allows for protein structures and functions to be studied. As proteins play a central role in biological systems and life itself, a deeper understanding of their structure-function properties is crucial to elucidating fundamental behaviors, such as protein folding in addition to the role that they play in emerging fields, such as, tissue engineering with application to the emerging field of regenerative medicine. However, a significant limitation toward achieving further advancements in this field is that in order to determine detailed structure of proteins from protein crystals, high-quality and larger size protein crystals are needed. Because it is difficult to produce adequate size, high-quality crystals, it remains difficult to determine the structure of many proteins. However, a new method using a microgravity environment to crystallize proteins has proven effective through various studies conducted on the International Space Station (ISS). In the presence of microgravity, free convection is essentially absent in the bulk solution where crystallization occurs, thus allowing for purely random Brownian motion to exist which favors the nucleation and growth of high-quality protein crystals. Many studies from the ISS to date have demonstrated that growing protein crystals in a microgravity environment produces larger and higher-quality crystals. This method provides new opportunities for better structure identification and analysis of proteins. Although there remains many more limitations and challenges in the field, microgravity protein crystallization holds many opportunities for the future of biotechnology and scientific development. The objective of this thesis was to study the crystallization of hen egg white lysozyme (HEWL) and determine the effects of both unit and microgravity on growth/size and quality of HEWL. Through preliminary trials using a universal ground-based reduced-gravity system, the crystallization of HEWL in a simulated microgravity environment was successfully conducted and the results reported are promising. The utility of continuous, scalable ground-based, microgravity platforms for studies on a wide range of material systems and behavior, such as, protein crystallization, has significant implications regarding its impact on many industries, including drug development as well as regenerative medicine.

Homeopathy is a brand of alternative medicine that has enjoyed a unique form of regulation for many years. This work aims to understand the regulation of homeopathic drugs in the United States by performing a literature review focused on three fronts: (i) homeopathy (theory, history in the United States and criticisms), (ii) U.S Food and Drug Administration (history and relationship to homeopathy), and (iii) interpretation of the law through reading guidance documents and the Code of Federal Regulations.
In 2015, the FDA began a process to reevaluate and update the regulations surrounding homeopathic products to better fit their present risk-based model. Past regulations were set in 1938; and as the world evolved, these have been found to set inadequate standards. By reviewing the agency’s guidance drafts and core regulatory documents, we come to understand that these changes are motivated by a desire for homeopathic remedies to follow high standards that apply to other products for the benefit of the U.S. consumers. FDA has made significant advances by proposing new Guidances on homeopathic products, listening to homeopathic community and consumers, and withdrawing the Compliance Policy Guide 400.400 issued in 1988.
We recommend for homeopathic manufacturers and practitioners to see the FDA as an ally and cooperate fully with the proposed changes for the regulation the agency gives out. Doing so will give the homeopathic community the best chance at continuing to sell their products and reach their consumers in the United States. In the same token, the FDA should do their best to involve homeopathic professionals in some way in this regulatory process, to encourage participation and compliance by the broader homeopathic community. Doing so ensures a climate of teamwork among different facets of the medical community in the United States.

Tissue engineering scaffold fabrication methods often have tradeoffs associated with them that prevent one method from fulfilling all design requirements of a desired scaffold. This undergraduate thesis seeks to combine 3D printing and electrospinning tissue engineering fabrication methods into a hybrid fabrication method that can potentially fulfill more design requirements than each method alone. The hybrid scaffolds were made by inserting electrospun scaffolds between layers of 3D printed scaffolds of increasing print temperature and effects on adhesion and mechanical properties were characterized. The fabrication method proved to be feasible and print temperature affected both adhesion and mechanical properties of the scaffolds. A positive, non-linear relationship was seen between print temperature and adhesion and resulting force. Insertion of electrospun mats led to increased damping of scaffolds. Evidence from characterization indicated factors other than print temperature were likely contributing to adhesion and mechanical properties. If studied further, this fabrication method could potentially be used to improve overall structure and regenerative potential of tissue engineering scaffolds.

The adaptive artificial-intelligence (AI) medical device industry is a novel industry in the United States offering innovations to the healthcare field. The rapid expansion of this industry in recent years has drawn attention from multiple stakeholders causing a heated debate about how to introduce these innovations into the market while maintaining patient safety and treatment efficacy. Since early 2019, the U.S. Food and Drug Administration (FDA) has been releasing statements in regards to the improvement of regulation for this new technology, but has yet to take further actions. Dilemmas including 1) a difficult regulatory process, 2) a heightening financial burden and 3) looming liability issues, are reasons adaptive AI medical devices have struggled to be advanced. By conducting a thorough analysis of these 3 issues, recognizing the intricacies of them separately and together, this study develops a better understanding of the landscape adaptive AI technology is facing and provides a clearer picture for the future of the industry.

The aim of the present study was to review the symptoms and current treatment options of the most common skin infections seen in outpatient settings and develop a preliminary alternative treatment solution. The specific skin infections evaluated were those caused by Staphylococcus and Streptococcus bacterial species, and are frequently treated with a wide variety of systemic antibiotics or topical ointments. Systemic antibiotics have shown increased occurrence of adverse side effects as well as the development of antibiotic-resistant bacteria. Additionally, these medications are usually overprescribed, which may further exacerbate negative side effects. Another issue that is addressed is the development of infections following treatment of a new laceration or other trauma to the skin. A patient may be treated for their wound with stitches or another alternative, but there is still the possibility of developing an infection later.
This study synthesizes information found from extensive research and provides a review of the most optimal techniques for developing an alternative to systemic antibiotics. The final deliverable is a report detailing the significant findings and discussing the ways that this solution may be developed further and implemented in a clinical setting. The solution is a hydrogel bandage designed to deliver antibiotics directly to the wound site, while also offering protection and enhanced wound healing. The target population is patients suffering from skin conditions in an outpatient setting. The antibiotics of interest for this solution are clindamycin, doxycycline, and trimethoprim-sulfamethoxazole (co-trimoxazole), as they offer excellent treatment against gram-positive bacteria and methicillin-resistant Staphylococcus aureus. However, other broad-spectrum antibiotics could potentially be incorporated to protect against gram-negative bacteria. The design features a polyvinyl alcohol (PVA) hydrogel that has shown many properties that are beneficial to biomedical applications, including biocompatibility, flexibility, high drug-loading capacity, high absorption of wound exudate, increased promotion of wound healing, and more. Preliminary mathematical models of the hydrogel’s drug delivery behaviors are also included. Due to the scope and timeframe of this project, the majority of findings herein are based on research of prior literature instead of development of the novel device. Future directions would include further research and development of the mechanisms behind the device, creation of a physical prototype, experimental testing, and statistical analyses to verify device specifications and capabilities.

This thesis aims to incorporate exosomes into an electrospun scaffold for tissue engineering applications. The motivation for this work is to develop an implant to regenerate tissue for patients with laryngeal defects. It was determined that it is feasible to incorporate exosomes into an electrospun scaffold. This addition of exosomes does alter the scaffold properties, by decreasing the average fiber diameter by roughly a factor of three and increasing the average modulus by roughly a factor of two. Cells were cultured on a scaffold with exosomes incorporated and were found to proliferate more than on a scaffold alone. This research lays the groundwork for further developing and optimizing an electrospun scaffold with exosomes incorporated to elicit a tissue regenerative response.

A point of care glucose sensor using electrochemical impedance spectroscopy (EIS) with a glutaraldehyde-linked enzyme shows promise as an effective biosensor platform. This report details the characterization of various factors on optimal binding frequency (OBF) and sensor performance to better prepare the sensor for future experimentation. Utilizing a screen printed carbon electrode, the necessary amount of glucose oxidase was determined to be 10 mg/mL. Binding time trials ranging from 1-3 minutes demonstrated that 1.5 minutes was the optimal binding time. This timeframe produced the strongest impedance response at each glucose concentration. Using this enzyme concentration and binding time, the native OBF of the biosensor was found to be 1.18 Hz using vector analysis. Temperature testing showed little change in OBF in sensors exposed to 4 \u00B0C through 43.3 \u00B0C. Only exposure to 60 \u00B0C resulted in rapid OBF change which was likely due to glucose oxidase becoming denatured. Humidity tests showed little change in OBF and sensor performance between sensors prepared at the humidities of 7.5%, 10.625% and 16.5% humidity. Alternatively, solutions containing common interference molecules such as uric acid, acetaminophen, and ascorbic acid resulted in a highly shifted OBF and drastically reduced signal.

A much anticipated outcome of the rapidly emerging field of personalized medicine is a significant increase in the standard of care afforded to patients. However, before the full potential of personalized medicine can be realized, key enabling technologies must be further developed. The purpose of this study was to use enabling technologies such as medical imaging, image reconstruction, and rapid prototyping to create a model of an implant for use in vocal fold repair surgery. Vocal fold repair surgery is performed for patients with great difficulty in phonation, breathing, and swallowing as a result of vocal fold damage caused by age, disease, cancer, scarring, or paralysis. This damage greatly hinders patients' social, personal, and professional lives due to difficulty in efficient communication. In this project, the image reconstruction of a subject's vocal fold in 3D is demonstrated utilizing NIH-funded advanced image processing software known as ITK-SNAP, which uniquely allows both semi-automatic and manual image segmentation. The hyoid bone, thyroid cartilage, arytenoid cartilage, and empty airway of the larynx were isolated using active contouring for use as anatomical benchmarks. Then, the vocal fold mold, including the vocal fold, a superior extension along the thyroid cartilage, and an inferior extension along the airway, was modeled with manual segmentation. The configured, isolated, and edited vocal fold model was converted into an STL file. This STL file can be imported to a 3D printer to fabricate a mold for reconstruction of a patient specific vocal fold biocompatible implant. This feasibility study serves as a basis to allow ENT surgeons at the Mayo Clinic to dramatically improve reparative surgery outcomes for patients. This work embodies the strategic importance of multidisciplinary teams working at the interface of technology and medicine to optimize patient outcomes.

Chronic stress has been linked as a probable contributor to a number of health problems that plague the world today. Obesity, cardiovascular disease, depression, and osteoporosis are all common health risks believed to be exacerbated by stress. While it is nether realistic nor desirable to completely eliminate stress in an individual, proper stress management is important to a healthy lifestyle. Homeostasis is the primary mechanism by which stress, and the stress response, should be analyzed. Environmental factors known as stressors elicit responses from the body, which can be measured in terms of duration and magnitude. These two factors determine the homeostatic response from the body. This thesis proposes the study of heart rate variability (HRV) to measure the response of the autonomic nervous system through time domain analysis (the length of interbeat intervals) and frequency domain analysis (the differences between the lengths of consecutive interbeat intervals). Even with many possible problems, this data still represents valuable proof of concept that HRV analysis may be of use in identifying stress.