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Structure-function study of N-isopropylacrylamide copolymers with enzyme degradable GAPGLF and GAPGLL side chains

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

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.

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2018-05

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Elution Profile of Caspofungin from Anti-fungal Loaded Bone Cement

Description

Advancements in healthcare and the emergence of an aging population has led to an increase in the number of prosthetic joint procedures in the United States. According to Healthcare Cost and Utilization Project, 660,876 and 348,970 total hip and knee

Advancements in healthcare and the emergence of an aging population has led to an increase in the number of prosthetic joint procedures in the United States. According to Healthcare Cost and Utilization Project, 660,876 and 348,970 total hip and knee arthroplasties were performed in 2014[1].The percentage of total hip or knee procedures that are revised due to an infection is 1.23% and 1.21% respectively[3], [4]. Although the percent of infections may be small, an infection can have a tremendous burden on the patient and healthcare system. It is expected that prosthetic joint infections (PJIs) will cost the healthcare system an estimated $1.62 billion by 2020[5]. PJIs are often difficult to treat due to the formation of biofilm at the site of the infection. A large majority of PJIs are the result of a bacterial biofilm, but around 1% of PJIs are due to fungal infections[3]. The current method of treatment is to surgically remove all infected tissue at the site of infection through a process called debridement and then insert a medicated bone cement spacer[7], [10]–[12]. One such medication that is loaded into the bone cement is caspofungin, a member of the echinocandin class of compounds that inhibit the synthesis of 1,3-β-D-glucan which is a crucial element of the cell wall of the target fungi[13]–[15]. For the studies reported herein, the caspofungin-loaded bone cement samples were made at 5 dosage strengths according to standard operating room practices. The elution of the drug was analyzed using ultraviolet spectrophotometry. The elution profiles were analyzed for 19 days consecutively, during which the 70 mg, 1 g, and 5 g dosage groups showed a prolonged, sustained release of the caspofungin. The 70 mg and 1 g dosage cumulative mass release profiles were not statistically significant, but it is unlikely that the difference would not have a clinical significance especially in the treatment of a fungal biofilm infection. The determination of the elution profile for caspofungin from loaded-bone cement can provide clinicians with a basis for how the drug will release into the infected joint.

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2019-05

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Norepinephrine and Adenosine Infused Microparticles for Brown Adipose Tissue Stimulation

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

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.

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2018-12

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Investigating the Role Of VEGF in Preeclampsia

Description

Preeclampsia is a condition which arises during pregnancy and can lead to serious, even fatal, complications for the mother and baby. Annually, preeclampsia is responsible for about 50,000 total deaths worldwide, and countless other complications for both the mother and

Preeclampsia is a condition which arises during pregnancy and can lead to serious, even fatal, complications for the mother and baby. Annually, preeclampsia is responsible for about 50,000 total deaths worldwide, and countless other complications for both the mother and fetus. While high blood pressure and protein in the urine are key features, symptoms vary widely, and thus understanding, diagnosing, and treating the condition is of paramount importance. Due to the correlation between preeclampsia and high blood pressure, multiple groups have studied the role of angiogenic growth factors and preeclampsia. We performed an advanced PubMed search to select studies with both preeclampsia and VEGF, a key growth factor for angiogenesis, in the title. The results of examining a total of 65 articles led to the formation of this review article to articulate the studies as a whole and state of the research on VEGF and preeclampsia to date.

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2020-05

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Drug Release from in \u2014 situ gelling material

Description

The main goal of this project was to study and understand the release of gentamicin from in – situ, self – reactive drug delivery gelling matrix. The motivation behind this was to create a drug delivery mechanism for gentamicin and

The main goal of this project was to study and understand the release of gentamicin from in – situ, self – reactive drug delivery gelling matrix. The motivation behind this was to create a drug delivery mechanism for gentamicin and eliminate the need for re–injecting the drug multiple times into the patient. Gentamicin is used to treat various different bacterial infections of the central nervous system, blood, kidneys, gall bladder, bile duct, heart cavity linings, and heart valves. Pentaerythritol–tetrakis
(3 – mercaptoproprionate; QT) was crosslinked with poly(ethylene glycol) diacrylate (PEGDA) having an average molecular weight of 575 with the help of Phosphate Buffer Saline (PBS), with a buffer ionic strength of 0.143M and a pH of 8.9 and 11, for the drug concentrations of 5 mg/mL and 50 mg/mL, respectively. The Michael – type reaction formed the crosslinked self – administering gelling matrix. With the gelling matrix starting to coagulate into a hydrophobic solid in about 5 minutes, the material was injected into Tygon tubing. After complete solidification, the drug – loaded gels were extracted from the tubing and divided into 1 cm cylinders. The cylinders with 5mg/mL and 50mg/mL drug concentration exhibited a sustained and controlled release curve for about 288 hours. This project as well as this drug delivery system can in the future be expanded for use in the delivery of more hydrophobic long – term drugs to the patient.

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2016-05

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The Effects of Material and Surface Properties on the Antimicrobial Susceptibility of Staphylococcal Biofilms

Description

Biofilm derived orthopedic infections are increasingly common after contamination of an open bone fracture or the surgical site pre- and post-orthopedic prosthetic insertion or removal. These infections are usually difficult to eradicate due to the resistant nature of biofilms to

Biofilm derived orthopedic infections are increasingly common after contamination of an open bone fracture or the surgical site pre- and post-orthopedic prosthetic insertion or removal. These infections are usually difficult to eradicate due to the resistant nature of biofilms to antimicrobial therapy. Difficulty of treatment of biofilm derived infections is also partly due to the presence of persister cells in the biofilm matrix. Persister cells are tolerant to antimicrobial therapy delivered via the systemic route. It is thus possible for these cells to repopulate their environment once systemic antimicrobial delivery is discontinued. The antimicrobial concentration required to eradicate bacterial biofilms, minimum biofilm eradication concentration (MBEC), can be determined in vitro by exposing biofilms to different regimens of antimicrobial solutions. Previous studies have demonstrated that values of the MBEC vary depending on the material and surface the biofilm grows on. This study investigated the relationship between antimicrobial susceptibility and antimicrobial exposure time, and the effects of surface material type on the antimicrobial susceptibility of staphylococcal biofilms. It was concluded that antimicrobial susceptibility increases with increased antimicrobial exposure time, and that the investigated surface and material properties did not have an effect on the susceptibility of staphylococcal biofilms to antimicrobial therapy. Further investigation is however necessary to confirm these results due to some inconsistent data obtained over the course of the trials.

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2016-05

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Hemodynamic Profiling of Endovascular Embolization Polymer Treatment of Cerebral Aneurysms

Description

Cerebral aneurysms, also known as intracranial aneurysms, are sac-like lesions in the arteries of the brain that can rupture to cause subarachnoid hemorrhaging, damaging and killing brain cells. Metal coil embolization has been traditionally used to occlude and treat cerebral

Cerebral aneurysms, also known as intracranial aneurysms, are sac-like lesions in the arteries of the brain that can rupture to cause subarachnoid hemorrhaging, damaging and killing brain cells. Metal coil embolization has been traditionally used to occlude and treat cerebral aneurysms to limited success, but polymer embolization has been suggested, because it can provide a greater fraction of occlusion. One such polymer with low cytotoxicity is poly(propylene glycol)diacrylate (PPODA) crosslinked via Michael-type addition with pentaerythritol tetrakis(3-mercaptopropionate) (QT). This study was performed to examine the behavior of PPODA-QT gel in vitro under pulsatile flow emulating physiological conditions. An idealized cerebral aneurysm flow model was designed based on geometries associated with an increase in rupture risk. Pressure was monitored at the apex of the aneurysm dome for varied flow rates and polymer filling fractions of 32.4, 78.2, and 100%. The results indicate that the amount of PPODA-QT deployed into the aneurysm decreases the peak-to-peak oscillation in pressure at the aneurysm wall by an inverse proportion. The 32.4 and 78.2% treatments did not significantly decrease the mean pressure applied to the aneurysm dome, but the 100% treatment greatly reduced it by diverting flow. This study indicates that the maximum filling fraction after swelling of PPODA-QT polymer should be deployed into the aneurysmal sac for treatment.

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2014-05

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Formulation Development and Evaluation of In-Situ Polymeric Drug Delivery Implants Formed by Tattooing

Description

This study demonstrates that a polymer and drug conjugate can be tattooed onto tissue and deliver drug in a sustained manner. A number of polymers and drugs were investigated in this study in the aims of developing a formulation that

This study demonstrates that a polymer and drug conjugate can be tattooed onto tissue and deliver drug in a sustained manner. A number of polymers and drugs were investigated in this study in the aims of developing a formulation that could achieve sustained drug delivery for 1-2 weeks. The polymers selected for testing were PDLG 5004, PDLLA-Glycerol, and PEG-PLA, and the drugs used in conjunction with these polymers were rifampicin, moxifloxacin, and dexamethasone. Varying formulas containing these polymer and drug combinations were tattooed onto three different tissue types: bovine pericardial tissue, porcine corneal tissue, and porcine sclera tissue. The drug release rates from these tattoos were determined and characterized after studying the release for up to 20 days. The release rate of dexamethasone from both PDLG 5004 and PDLLA-Glycerol when tattooed onto bovine pericardial tissue demonstrated the best release rate of the formulations tested, with up to 14 days of sustained release. This preliminary research into tattoo-based, polymeric drug delivery is promising, and has the possibility to be developed into a beneficial form of ophthalmic drug delivery that could be expanded to other areas of treatment as well.

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2016-05

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Revision Hip Arthroplasties: The burdens created due to physical compromise and biofilm formation

Description

Revision hip procedures represent a large financial burden on hospitals and the problem will continue to worsen as the baby boomer generation ages and life expectancy goes up. The future problem is a complex issue that bridges scientific and anecdotal

Revision hip procedures represent a large financial burden on hospitals and the problem will continue to worsen as the baby boomer generation ages and life expectancy goes up. The future problem is a complex issue that bridges scientific and anecdotal evidence and must be solved. A review of the current total hip arthroplasty procedure in regards to the physical properties of the materials used for hip prostheses is given. Revision procedures can be caused by infection or basic wear and tear from the stress that that implant is subjected to daily. Infections on these implants often present themselves as medical biofilms. The mechanisms of biofilm formation include a complex system of enzymes that work to initiate a phenotypic response based on an established quorum sensing within the colony of bacteria. Surgical methods to treat infection include irrigation and debridement as well as loading drug cement spacers with antimicrobial in hopes of delivering the antibiotic locally. Research is being done to better model the transport of drug through the tissue surrounding the implant, and will hopefully one day be available for use in individual patients.

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2013-05

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The Characterization and Development of Methylcellulose in Hydrogels

Description

This report provides information concerning qualities of methylcellulose and how those properties affect further experimentation within the biomedical world. Utilizing the compound’s biocompatibility many issues, ranging from surgical to cosmetic, can be solved. As of recent, studies indicate,

This report provides information concerning qualities of methylcellulose and how those properties affect further experimentation within the biomedical world. Utilizing the compound’s biocompatibility many issues, ranging from surgical to cosmetic, can be solved. As of recent, studies indicate, methylcellulose has been used as a physically cross-linked gel, which cannot sustain a solid form within the body. Therefore, this report will ultimately explore the means of creating a non-degradable, injectable, chemically cross-linking methylcellulose- based hydrogel. Methylcellulose will be evaluated and altered in experiments conducted within this report and a chemical cross-linker, developed from Jeffamine ED 2003 (O,O′-Bis(2-aminopropyl) polypropylene glycol-block-polyethylene glycol-block-polypropylene glycol), will be created. Experimentation with these elements is outlined here, and will ultimately prompt future revisions and analysis.

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2013-05