Master of Science / Department of Clinical Sciences / Walter C. Renberg / Objective: To compare the in vitro elution characteristics of six common analgesic medications from a commercially available absorbable gelatin sponge. Study Design: Experimental study. Methods: Gelatin sponges were loaded with various analgesic medications, including two opioids, preservative-free morphine and fentanyl, two local anesthestics, bupivacaine and lidocaine, and two α2-adrenergic agonists, dexmedetomidine and xylazine. The loaded sponges were placed in dishes containing phosphate-buffered saline (PBS) and maintained at 37° C with constant agitation. Concentrations of each drug were determined at various time points up to 24 hours post-inoculation using high-pressure liquid chromatography. Two phases were conducted, utilizing undried loaded sponges (phase one) and dried loaded sponges (phase two). Results: In both phases, all analgesic medications eluted from the gelatin sponge and equilibrated rapidly with the PBS, achieving maximal concentration within 30 minutes. In phase two, the rapid nature of the release was captured by increasing sampling within the initial 30 minutes. Results were consistent for each medication with minimal variation. Steady state concentrations were significantly higher in phase two with four out of six medications. Conclusions: Analgesic medication elution from an absorbable gelatin sponge was rapid and consistent. Drying the loaded sponge prior to use will likely substantially increase the amount of medication eluted but not prolong release. Clinical Relevance: The rapid release of analgesic medications from the gelatin sponge makes a prolonged analgesic effect unlikely without further modification. Toxicity may be a concern. Further study is required to investigate efficacy in vivo, safe dosing regimens and prolongation of duration of action.

Abdominal aortic aneurysms are a leading cause of death in the U.S. where 14,000 people die from aneurysm rupture and 178,000 are diagnosed each year. A novel alternative treatment for abdominal aortic aneurysms has been proposed, where a biodegradable polymer scaffold is photopolymerized in situ around the exterior of the aneurysm. This scaffold will mechanically constrain the aneurysm from further expansion, and will deliver a drug, doxycycline, to treat the underlying biological cause of the disease. In order for device development, a suitable polymer must be designed with appropriate mechanical properties, degradation rate, polymerization, and elution rate. Poly(β-amino ester) networks have been proposed as the material of choice; however, many of their structure-property relationships have yet to be determined. Therefore, the overall goal of this work is to determine the structure-property relationships of the poly(β-amino ester) networks in order to advance the design of the treatment, and has been divided into three objectives: (1) understand the structure-property relationships of poly(β-amino ester) networks, specifically the polymerization, degradation rate, and thermo-mechanical properties, (2) determine the impact of doxycycline incorporation on degradation rate and mechanical properties, (3) evaluate the effect of simulated physiological conditions on degradation rate and mechanical properties. In the initial chapters, the fundamental structure-property relationships are established between reactant chemical structure, step-growth polymerization, photopolymerization, thermo-mechanical properties, and degradation rate using a systematic approach of two homologous series of reactants. Further tailoring of degradation rate, water content, and modulus in vitro was performed by using a copolymer network. Doxycycline inhibited photopolymerization due to overlapping absorbance spectra with the photoinitiator, but full network formation occurred by increasing the photoinitiator concentration. Networks displayed varying controlled release rates, and the underlying release mechanism was determined for each network using established methods. In order to increase mechanical properties, a co-monomer, methyl methacrylate, was added to the network to increase the glass transition temperature, toughness, and deformation capacity. These co-networks displayed temporal-control of mechanical properties in simulated physiological conditions, since degradation caused a shift in the glass transition temperature, which changed the mechanical behavior of the network. The temporal-control of mechanical properties was further investigated under degradation conditions in vitro and in vivo. Due to the mechanically active loading environment in vivo, networks displayed a decrease in toughness, yet maintained mechanical properties similar to native biological tissues. These networks establish a multifunctional biomaterials platform with materials that can be easily synthesized, photopolymerized into various geometries, and sustain mechanical properties while undergoing degradation and therapeutic agent release.