Aminoglycosides contain a basic unit of an amino-modified glycoside (sugar) and have potent antibacterial properties used to treat a wide range of bacterial infections, including those that occur in the soft tissue, chest, urinary tract, and endocardial tissue.1, 2 With a broad spectrum of activity and convenient dosing schedule, Aminoglycoside helps to effectively fight off Gram-negative bacteria.1, 3 In 1944 an aminoglycoside called streptomycin entered clinical trials to test its effectiveness as an antibiotic.4 After several years other classes of aminoglycosides were discovered such as neomycin, gentamicin, kanamycin, and netilmicin.4 When introduced these antibiotics presented major clinical advancements in the treatment of Tuberculosis and other bacterial infections.3, 4 However their use in modern medicine has diminished due to their toxicity, required parenteral delivery, and the availability of alternative antibiotics.3, 5 The dose-dependent toxicity of aminoglycosides limits their use due to a narrow range of safe aminoglycoside plasma concentrations.3, 5 Exceeding this range in non-target tissues can lead to negative effects on the audio-vestibular apparatus and kidneys.3, 5, 6 In the 1980’s, clinicians began treating infections with antibiotics that were perceived as less toxic and providing broader antibacterial activity.7 This resulted in aminoglycosides being prescribed for more persistent infections that were resistant to other antibiotics.3 With the amount of antibiotic resistant bacteria increasing, many scientists have begun looking into methods for minimizing aminoglycoside toxicity and maximizing its antibacterial activity.3, 8 These methods include encapsulation and polymer conjugation.9, 10 By encapsulating aminoglycosides in liposomes or other vesicles scientists aim to increase its concentration in infected tissues while decreasing nephro- and ototoxicity.9 With conjugated polymers scientists have created polymer complexes containing aminoglycosides and other compounds such as dopamine.11 The goal of these polymers is to limit toxicity by slowing antibiotic release and increasing efficacy of the antibiotic through targeted delivery and toxicity of other compounds.9, 10, 11 Other than its use in treating infections, aminoglycosides are gaining attention as an excellent vehicle for gene delivery.12 In this application aminoglycosides are used to correct a genetic defect by introducing a normal copy of the gene into affected cells.12,13 Currently scientists are assessing aminoglycosides for gene therapy in the treatment of cancer and various other diseases.12, 14 This review will focus on the diverse customizability of aminoglycosides in treating infections and as vehicles for gene therapy.

Chronic wounds affect many people worldwide and significantly impact their quality of life. Hydrogel wound dressings are a promising option for chronic wounds due to their properties, including mild fabrication conditions, high water content, biodegradability, and bioactive molecule delivery capabilities. This thesis will explore the mechanisms that contribute to the wound healing properties of a bovine type I collagen-based hydrogel that incorporates platelet-rich plasma and describe how this hydrogel will be capable of effectively healing chronic wounds.

In 2012, a team of scientists across the US conducted an experiment to find the mechanism that allowed a group of flatworms, planarians, to regenerate any body part. The group included Danielle Wenemoser, Sylvain Lapan, Alex Wilkinson, George Bell, and Peter Reddien. They aimed to identify genes that are expressed by planarians in response to wounds that initiated a regenerative mechanism. The researchers determined several genes as important for tissue regeneration. The investigation helped scientists explain how regeneration is initiated and describe the overall regenerative mechanism of whole organisms.

The current clinical gold standards for tissue sealing include sutures, staples, and glues, however several adverse effects limit their use. Sutures and staples inherently cause additional trauma to tissue surrounding the wound, and glues can be lacking in adhesion and are potentially inflammatory. All three also introduce risk of infection. Light-activated tissue sealing, particularly the use of near-infrared light, is an attractive alternative, as it localizes heat, thereby preventing thermal damage to the surrounding healthy tissue. Previous work identified a glutaraldehyde-crosslinked chitosan film as a lead sealant for gastrointestinal incision sealing, but in vivo testing resulted in tissue degradation in and around the wound. The suggested causes for this degradation were excess acetic acid, endotoxins in the chitosan, and thermal damage. A basic buffer wash protocol was developed to remove excess acid from the films following fabrication. UV-Vis spectroscopy demonstrated that following the wash, films had the same concentration of Indocyanine green as unwashed films, allowing them to absorb light at the same wavelength, therefore showing the wash did not affect the film’s function. However subsequent washes led to degradation of film mass of nearly 20%. Standard chitosan films had significantly greater mass gain (p = 0.028) and significantly less subsequent loss (p= 0.012) than endotoxin free chitosan-films after soaking in phosphate buffered saline for varying durations , while soaking duration had no effect (p = 0.332). Leak pressure testing of films prepared with varying numbers of buffer washes, laser temperature, and lasering time revealed no significant interaction between any of the 3 variables. As such, it was confirmed that proceeding with in vivo testing with the buffer wash, various lasering temperatures, and laser times would not affect the sealing performance of the films. Future investigation will involve characterization of additional materials that may be effective for sealing of internal wounds, as well as drug loading of agents that may hasten the healing process.