Biomedical Engineering and Bioengineering Commons^™

Engineering Hydrogels For Delivery Of Therapeutic Proteins, Francesca Briggs, Daryn Browne

Bioengineering Senior Theses

In this project, we investigate how innate hydrogel properties can be leveraged for controlled protein drug release platforms. Therapeutic proteins have many valuable applications within the medical field, however, professionals often face many obstacles with obtaining controlled drug release. This paper analyzes how the manipulation of hydrogel properties can improve protein drug release rates. We started these investigations by varying hydrogel concentrations since we saw that this affects the release of small molecules. Additionally, we wanted to see what the addition of a second hydrogel network would do to protein release rates. These experiments concluded that raising polymer concentrations and …

Nanoparticulate Carriers For Drug Delivery, Samantha Lokelani Crossen, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

Drug delivery with nanoparticulate carriers is a new and upcoming research area that is making major changes within the pharmaceutical industry. Nanoparticulate carriers are discussed, particularly, engineered nanoparticulate carriers used as drug delivery systems for targeted delivery. Nanoparticulate carriers that are used for drug delivery systems include polymers, micelles, dendrimers, liposomes, ceramics, metals, and various forms of biological materials. The properties of these nanoparticulate carriers are very advantageous for targeted drug delivery and result in efficient drug accumulation at the targeted area of interest, reduced drug toxicity, reduced systemic side effects, and more efficient use of the drug overall. Nanoparticlulate …

Novel Stimuli-Responsive Pectin-Pvp-Functionalized Clay Based Smart Hydrogels For Drug Delivery And Controlled Release Application, Shabnam Rehmat, Nayab Batool Rizvi, Saba Urooge Khan, Abdul Ghaffar, Atif Islam, Rafi Ullah Khan, Azra Mehmood, Hira Butt, Muhammad Rizwan

Michigan Tech Publications, Part 1

Stimuli-responsive drug delivery systems are urgently required for injectable site-specific delivery and release of drugs in a controlled manner. For this purpose, we developed novel pH-sensitive, biodegradable, and antimicrobial hydrogels from bio-macromolecule pectin, polyvinylpyrrolidone (PVP), 3-aminopropyl (diethoxy)methyl silane (3-APDEMS), and sepiolite clay via blending and solution casting technique. The purified sepiolite (40 um) was functionalized with 3-APDEMS crosslinker (ex-situ modification) followed by hydrogels fabrication. FTIR and SEM confirmed crosslinked structural integrity and rod-like morphology of hydrogels respectively. The swelling properties of hydrogels could be controlled by varying the concentration of modified clay in pectin/PVP blends. Moreover, the decrease in pH …

Transdermal Drug Delivery Systems: Analysis Of Adhesion Failure, Zachary Brooks, Tushar Goswami, Amy Neidhard-Doll, Tarun Goswami

Biomedical, Industrial & Human Factors Engineering Faculty Publications

The most critical component of the TDDS is the adhesive, which is responsible for the safety, efficacy and quality of the patch. For drug delivery to successfully occur, the patch must adhere to the surface of the contact area. If a patch has inadequate adhesion, it is likely to fall off before the entire delivery period has been satisfied, leading to risks for the patient and others who may encounter the patch. Despite the critical concerns associated with the adhesive properties of the patches, the adhesion quality and failure mechanisms have not been fully studied. If certain molecules encounter the …

Immunomodulatory Biomaterials For Cancer Immunotherapy, Larry Donnell Stokes Jr

Honors Theses

Cancer immunotherapy has become an effective treatment in the toolbox of oncologists. Immunotherapy offers a less toxic alternative to standard cancer treatments such as chemotherapy and can have prolonged curative effects to decrease cancer recurrence. Today, many drugs and biological agents have been developed that target the immune system and elicit an antitumor/cancer response. These agents are known collectively as cancer immunotherapies. While immunotherapies have radically improved treatment outcomes for many cancer patients, there are drawbacks to using these treatments. Immunotherapy treatments have poor clinical responses in patients with tumors that lack immunogenicity. Some of the treatments also pose a …

Evaluating The Structural And Functional Consequences Of Traumatic Joint Injury And Their Relation To Nf-Κb In A Non-Invasive Model Of Post-Traumatic Osteoarthritis, Ian Matthew Berke

McKelvey School of Engineering Graduate Student Theses & Dissertations

Post-traumatic osteoarthritis (PTOA) is a painful and debilitating disease of the synovial joint, characterized by degenerative changes to various joint tissues following traumatic joint injury. While several risk factors have been identified in the symptomatic progression of PTOA following injury, inflammation and NF-κB mediated changes are believed to significantly contribute to symptomatic joint dysfunction and pain. However, the temporal presentation of these pro-inflammatory signals following clinically relevant injury and their relationship to the development of symptomatic disease have not been thoroughly investigated. Therefore, there exists a critical need to better understand how these early inflammatory events following injury may contribute …

Recent Advances In The Redox-Responsive Drug Delivery Nanoplatforms: A Chemical Structure And Physical Property Perspective, Shirin Mollazadeh, Marcin Mackiewicz, Mostafa Yazdimamaghani

Chemical and Biochemical Engineering Faculty Research & Creative Works

Poor water solubility, off-target toxicity, and small therapeutic window are among major obstacles for the development of drug products. Redox-responsive drug delivery nanoplatforms not only overcome the delivery and pharmacokinetic pitfalls observed in conventional drug delivery but also leverage the site-specific delivery properties. Cleavable diselenide and disulfide bonds in the presence of elevated reactive oxygen species (ROS) and glutathione concentration are among widely used stimuli-responsive bonds to design nanocarriers. This review covers a wide range of redox-responsive chemical structures and their properties for designing nanoparticles aiming controlled loading, delivery, and release of hydrophobic anticancer drugs at tumor site.

The Use Of Nanoparticles And Electrospun Fibers For Intravaginal Delivery To Treat Viral And Bacterial Infections And Electrophysiological Measurements Of Synthetic Chloride Channels., Farnaz Minooei

Electronic Theses and Dissertations

Female reproductive viral and bacterial infections affect millions of women worldwide. Given the diversity and magnitude of these unmet reproductive health challenges, topical administration of antiretrovirals (ARVs) and antibiotics have emerged as promising approaches to maintain and restore reproductive health. However, currently available intravaginal dosage forms often suffer from low user adherence and the need for frequent, daily administration to achieve therapeutic effect. To address these challenges, the broad goal of this research was to focus on the development of new localized nanoparticle (NP) and electrospun fiber dosage forms to prolong the delivery and enhance the efficacy of active agents …

Aligned Fingolimod-Releasing Electrospun Fibers Increase Dorsal Root Ganglia Neurite Extension And Decrease Schwann Cell Expression Of Promyelinating Factors, Devan L. Puhl, Jessica L. Funnell, Anthony R. D'Amato, Jonathan Bao, Dmitri V. Zagorevski, Yelena Pressman, Daniel Morone, Agnes E. Haggerty, Martin Oudega, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

Researchers are investigating the use of biomaterials with aligned guidance cues, like those provided by aligned electro spun 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 drug fingolimod improved peripheral nerve regeneration in preclinical rodent models by stimulating a pro-regenerative Schwann cell phenotype and axonal growth. However, the systemic delivery of fingolimod for nerve repair can lead to adverse effects, so it is necessary to develop a means of providing sustained delivery of fingolimod local to the injury. …

Polymeric Nanoparticles As An Antioxidant Delivery System For Age-Related Eye Disease, Sean M. Swetledge

LSU Doctoral Dissertations

Advantages of polymeric nanoparticles as ocular drug delivery systems include controlled release, enhanced drug stability and bioavailability, and specific tissue targeting. Nanoparticle properties such as hydrophobicity, size, and charge, mucoadhesion, as well as administration route and suspension media affect their ability to overcome ocular barriers and distribute in the eye, and must be carefully designed for specific target tissues and ocular diseases. A review was conducted to serve as a guide to optimizing polymeric nanoparticle delivery systems for ocular drug delivery by discussing the effects of nanoparticle composition and administration method on their ocular penetration, distribution, elimination, toxicity, and efficacy, …

Thermoresponsive Nanogels Based On Different Polymeric Moieties For Biomedical Applications, Sobhan Ghaeini-Hesaroeiye, Hossein Razmi Bagtash, Soheil Boddohi, Ebrahim Vasheghani-Farahani, Esmaiel Jabbari

Faculty Publications

Nanogels, or nanostructured hydrogels, are one of the most interesting materials in biomedical engineering. Nanogels are widely used in medical applications, such as in cancer therapy, targeted delivery of proteins, genes and DNAs, and scaffolds in tissue regeneration. One salient feature of nanogels is their tunable responsiveness to external stimuli. In this review, thermosensitive nanogels are discussed, with a focus on moieties in their chemical structure which are responsible for thermosensitivity. These thermosensitive moieties can be classified into four groups, namely, polymers bearing amide groups, ether groups, vinyl ether groups and hydrophilic polymers bearing hydrophobic groups. These novel thermoresponsive nanogels …

Pilot Study Exploring The Effect Of Targeted Cox-2 Inhibition In Macrophages Responding To Neuronal Injury; Promoting Enhanced Axonal Regeneration, Alyssa Brauckmann

Electronic Theses and Dissertations

Celecoxib nanoemulsion (CXB-NE) has been developed as a macrophage targeted analgesics by Dr. Janjic and her team at Duquesne University, (Janjic et al, 2018; Liu et al, 2020; Saleem et al, 2019b; Vasudeva et al, 2014). The CXB-NE nanoemulsion carrying a Nonsteroidal Anti-inflammatory (NSAID) inhibitor of COX-2 activity result in a reduction in PGE2 expression in macrophages. Using CXB-NE in rats that have peripheral nerve injury constricting the sciatic nerve relieves hypersensitivity, a pain-like behavior. The treatment also decreases inflammation associated with this chronic constriction injury (Janjic et al, 2018; Saleem et al, 2019b; Stevens et al, 2019). In this …

Surface Modification Of Titanium For Orthopedic And Drug Delivery Applications, Prantik Roy Chowdhury

Graduate Research Theses & Dissertations

Titanium is one of the most attractive metal used in orthopedic and drug delivery applications because of its excellent mechanical properties, biocompatibility and high corrosion resistance. However, due to its bio-inertness, fibrous tissue forms between the bone and implant which causes loosening of implant. Surface modification can play an important role to enhance interaction between implant and the surrounding tissues which reduces the implant failure. The aim of this study is to a) incorporate magnesium (Mg) into modified titanium surface by different deposition methods for bone-implant interaction, b) modify the surface of titanium by alkali treatment, and c) investigate the …

Application Of Micro-Scale 3d Printing In Pharmaceutics, Andrew Kjar, Yu Huang

Biological Engineering Faculty Publications

3D printing, as one of the most rapidly-evolving fabrication technologies, has released a cascade of innovation in the last two decades. In the pharmaceutical field, the integration of 3D printing technology has offered unique advantages, especially at the micro-scale. When printed at a micro-scale, materials and devices can provide nuanced solutions to controlled release, minimally invasive delivery, high-precision targeting, biomimetic models for drug discovery and development, and future opportunities for personalized medicine. This review aims to cover the recent advances in this area. First, the 3D printing techniques are introduced with respect to the technical parameters and features that are …

Development And Evaluation Of Biocompatible Engineered Nanoparticles For Use In Ophthalmology, Bedia Begum Karakocak

McKelvey School of Engineering Graduate Student Theses & Dissertations

The synthesis and design of biocompatible nanoparticles for targeted drug delivery and bioimaging requires knowledge of both their potential toxicity and their transport. For both practical and ethical reasons, evaluating exposure via cell studies is a logical precursor to in vivo tests. As a step towards clinical trials, this work extensively investigated the toxicity of gold nanoparticles (Au NPs) and carbon dot (CD) nanoparticles as a prelude to their in vivo application, focusing specifically on ocular cells. As a further step, it also evaluated their whole-body transport in mice. The research pursued two approaches in assessing the toxicity of engineered …

Thermal Fluid Models Of A Hydrogel Delivery System For Pancreatic Cancer Treatment, Nesrine Bouhrira

Theses and Dissertations

Pancreatic cancer is one of the most devastating cancers with low survival rates. This disease is difficult to detect due to the pancreas's location deep within the body. Therefore, diagnoses are often made in the later stages, making treatment options more limited and difficult. It has been hypothesized that direct injection into the tumor would enhance drug effectivenes. Therefore, we examined the use of endoscopic ultrasound (EUS) combined with a fine needle injection to deliver a drug-eluding thermosensitive hydrogel directly into the tumor. Unfortunately normal body temperatures surrounding the EUS can warm the hydrogel drug combination beyond its phase transition …

Tuning Properties Of Poly(Ethylene Glycol)-Block-Poly(Simvastatin) Copolymers Synthesized Via Triazabicyclodecene, Theodora A. Asafo-Adjei, Thomas D. Dziubla, David A. Puleo

Biomedical Engineering Faculty Publications

Simvastatin was polymerized into copolymers to better control drug loading and release for therapeutic delivery. When using the conventional stannous octoate catalyst in ring-opening polymerization (ROP), reaction temperatures ≥ 200 °C were required, which promoted uncontrollable and undesirable side reactions. Triazabicyclodecene (TBD), a highly reactive guanidine base organocatalyst, was used as an alternative to polymerize simvastatin. Polymerization was achieved at 150 °C using 5 kDa methyl-terminated poly(ethylene glycol) (mPEG) as the initiator. ROP reactions with 2 kDa or 550 Da mPEG initiators were also successful using TBD at 150 °C instead of stannous octoate, which required a higher reaction temperature. …

Delivery Of Antioxidant And Anti-Inflammatory Agents For Tissue Engineered Vascular Grafts, Kenyatta S. Washington, Chris A. Bashur

Biomedical Engineering and Sciences Faculty Publications

The treatment of patients with severe coronary and peripheral artery disease represents a significant clinical need, especially for those patients that require a bypass graft and do not have viable veins for autologous grafting. Tissue engineering is being investigated to generate an alternative graft. While tissue engineering requires surgical intervention, the release of pharmacological agents is also an important part of many tissue engineering strategies. Delivery of these agents offers the potential to overcome the major concerns for graft patency and viability. These concerns are related to an extended inflammatory response and its impact on vascular cells such as endothelial …

Removal Of Retained Electrospinning Solvent Prolongs Drug Release From Electrospun Plla Fibers, Anthony R. D'Amato, Nicholas J. Schaub, Jesus M. Cardenas, Andrew S. Fiumara, Paul M. Troiano, Andrea Fischetti, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

A major challenge in developing drug-releasing electro spun nanofibers is obtaining long-term drug release over many weeks with no burst release of drug. Here, we present new methods capable of prolonging the diffusive release of small molecule drugs from electro spun poly-L-lactic acid (PLLA) nanofibers. The methods focus on removal of retained electrospinning solvent through fiber heating, maintaining fibers in a laboratory setting, or a combination of these methods. These post-fabrication methods altered the release characteristics of a model small molecule drug, 6-aminonicotinamide (6AN), from PLLA fibers. Specifically, untreated fibers released 6AN over 9 days, and fibers that underwent a …

Redox-Responsive Polysulfide-Based Biodegradable Organosilica Nanoparticles For Delivery Of Bioactive Agents, Seyyed Pouya Hadipour Moghaddam, Jiban Saikia, Mostafa Yazdimamaghani, Hamidreza Ghandehari

Chemical and Biochemical Engineering Faculty Research & Creative Works

Design and development of silica nanoparticles (SiO2 NPs) with a controlled degradation profile promises effective drug delivery with a predetermined carrier elimination profile. In this research, we fabricated a series of redox-responsive polysulfide-based biodegradable SiO2 NPs with low polydispersity and with variations in size (average diameters of 58 ± 7, 108 ± 11, 110 ± 9, 124 ± 9, and 332 ± 6 nm), porosity, and composition (disulfide vs tetra sulfide bonds). The degradation kinetics of the nanoparticles was analyzed in the presence of 8 mM glutathione (GSH), mimicking the intracellular reducing condition. Results indicate that porosity and core composition …

Biomaterials For Local, Controlled Drug Delivery To The Injured Spinal Cord, Alexis M. Ziemba, Ryan J. Gilbert

Chemical and Biochemical Engineering Faculty Research & Creative Works

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 point. With this review, we aim to communicate the importance of combinatorial biomaterial and pharmacological approaches that target certain aspects of the dynamically changing pathophysiology of SCI. After reviewing the pathophysiology timeline, we present experimental biomaterial approaches to provide local sustained doses of drug. In this review, we present …

Synthesis And Characterization Of Poly(Simvastatin) - Incorporated Copolymers And Blends For Bone Regeneration, Theodora Asafo-Adjei

Theses and Dissertations--Biomedical Engineering

Common biodegradable polyesters such as poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA) and poly(ε-caprolactone) (PCL) are used as drug delivery vehicles for tissue regenerative applications. However, they are typically bioinert, with drug loading limitations. Polymerizing the active agent or precursor into its respective biodegradable polymer would control drug loading via molar ratios of drug to initiator used for synthesis. Simvastatin was chosen due to its favorable anti-inflammatory, angiogenic, and osteogenic properties. In addition, its lactone ring lends itself to ring-opening polymerization and, consequently, the synthesis of poly(simvastatin) with controlled simvastatin release.

Simvastatin was first polymerized with a 5kDa methyl-terminated poly(ethylene glycol) …

Calcium Phosphate As A Key Material For Socially Responsible Tissue Engineering, Vuk Uskoković, Victoria M. Wu

Pharmacy Faculty Articles and Research

Socially responsible technologies are designed while taking into consideration the socioeconomic, geopolitical and environmental limitations of regions in which they will be implemented. In the medical context, this involves making therapeutic platforms more accessible and affordable to patients in poor regions of the world wherein a given disease is endemic. This often necessitates going against the reigning trend of making therapeutic nanoparticles ever more structurally complex and expensive. However, studies aimed at simplifying materials and formulations while maintaining the functionality and therapeutic response of their more complex counterparts seldom provoke a significant interest in the scientific community. In this review …

Design Of A Drug Delivery System Through The Gastrointestinal Tract, Kaixin Chen, Adel Husayni, Kayvon Mobarakeh, Ankit Soni

Capstone Design Expo Posters

Alzheimer’s Disease (AD) afflicts an estimated 5.3 million individuals and is the sixth leading cause of death in America. The drug delivery method of interest is an orally administered sustained-release delivery system that addresses the needs of the associated patient population. By augmenting drug delivery with a higher effective payload per dose compared to current methods, drug efficacy and bioavailability would improve. This will result in a decrease of the overall cost for medication as a greater percentage of the administered drug will be viable.

This design addresses the release of AD drug from the drug delivery system at the …

Fe3o4 Nanoparticles For Magnetic Hyperthermia And Drug Delivery: Synthesis, Characterization And Cellular Studies, Maheshika Palihawadana Arachchige

Wayne State University Dissertations

In recent years, magnetic nanoparticles (MNPs), especially superparamagnetic Fe3O4nanoparticles, have attracted a great deal of attention because of their potential applications in biomedicine. Among the other applications, Magnetic hyperthermia (MHT), where localized heating is generated by means of relaxation processes in MNPs when subjected to a radio frequency magnetic field, has a great potential as a non-invasive cancer therapy treatment. Specific absorption rate (SAR), which measures the efficiency of heat generation, depends on magnetic properties of the particles such as saturation magnetization (Ms), magnetic anisotropy (K), particle size distribution, magnetic dipolar interactions, and the rheological properties of the target medium.We …

Ultrasound-Guided Nanobubbles For Targeted Drug Delivery, Pei Yang, Pushpak Bhandari, Joseph Irudayaraj

The Summer Undergraduate Research Fellowship (SURF) Symposium

In a large number of biological and environmental applications, ultrasound (US)-powered micro- and nano-motors have attracted considerable attention. However, their applications in biological settings have been limited due to the incompatibility of metallic motors and the lack of precision guiding. Here, we demonstrate that cellulosic polymer nanobubbles (200-800nm) can be propelled, aligned, accelerated, and assembled in solution using Doppler ultrasound beam (DUB) and simultaneously imaged using low-frequency ultrasound. Results show that by utilizing Doppler ultrasound beam (DUB), nanobubbles accumulation at a pre-determined site can be enhanced. Moreover, bubbles’ trajectory and velocity can be also be manipulated. Related parameters associated with …

Design And Development Of Two Component Hydrogel Ejector For Three-Dimensional Cell Growth, Thomas Dunkle, Jessica Deschamps, Connie Dam

Honors Scholar Theses

Hydrogels are useful in wound healing, drug delivery, and tissue engineering applications, but the available methods of injecting them quickly and noninvasively are limited. The medical industry does not yet have access to an all-purpose device that can quickly synthesize hydrogels of different shapes and sizes. Many synthesis procedures that have been developed result in the formation of amorphous hydrogels. While generally useful, amorphous hydrogels exhibit limited capability in tissue engineering applications, especially due to their viscous properties. This endeavor aims to modulate the appropriate gelation parameters, optimize the injection process, and create a prototype that allows for the extrusion …

Biomimetic Oral Mucin From Polymer Micelle Networks, Sundar Prasanth Authimoolam

Theses and Dissertations--Chemical and Materials Engineering

Mucin networks are formed by the complexation of bottlebrush-like mucin glycoprotein with other small molecule glycoproteins. These glycoproteins create nanoscale strands that then arrange into a nanoporous mesh. These networks play an important role in ensuring surface hydration, lubricity and barrier protection. In order to understand the functional behavior in mucin networks, it is important to decouple their chemical and physical effects responsible for generating the fundamental property-function relationship. To achieve this goal, we propose to develop a synthetic biomimetic mucin using a layer-by-layer (LBL) deposition approach. In this work, a hierarchical 3-dimensional structures resembling natural mucin networks was generated …

Layered, Flexible Drug Delivery Films For The Prevention Of Fibrotic Scar Tissue Formation, Cheryl L. Rabek

Theses and Dissertations--Biomedical Engineering

Open wounds account for about 50% of military injuries and 10% of non‐fatal traffic injuries. Scar tissue formation in these wounds may be reduced or prevented if treated with a combination of molecules whose release is tuned to the healing phases. The goal of this research was to develop flexible, layered drug delivery films for sequential, localized release of anti‐inflammatory, anti‐oxidant, and anti‐fibrotic molecules to soft tissue.

Films were composed of cellulose acetate phthalate (CAP) and Pluronic F‐127 (Pluronic). To impart flexibility, plasticizers, triethyl citrate (TEC) or tributyl citrate (TBC), were added. Mechanical analysis was performed on films as prepared …

A Local, Sustained Delivery System For Zoledronic Acid And Rankl-Inhibitory Antibody As A Potential Treatment For Metastatic Bone Disease, Rohith Jayaram

Theses and Dissertations--Biomedical Engineering

Cancerous solid tumors can migrate and lead to metastatic bone disease. Drugs prescribed to reduce bone resorption from metastasis, such as zoledronic acid and the RANKL-inhibitory antibody Denosumab, cause side effects such as osteonecrosis of the jaw when delivered systemically. This project used two biocompatible materials, acrylic bone cement (PMMA) and poly(lactic-co-glycolic acid) (PLGA), to incorporate and sustain release of anti-resorptive agents. Results showed similar mechanical properties for acrylic bone cements loaded up to 6.6% drug by weight. Results showed sustained zoledronic acid release for 8 weeks from both systems, with PMMA releasing up to 22% of loaded drug and …