Browsing by Author "Kimicata, Megan"
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Item DECELLULARIZED PERICARDIUM/POLY(PROPYLENE FUMARATE) BIOHYBRID SCAFFOLDS FOR SMALL DIAMETER VASCULAR GRAFTS(2021) Kimicata, Megan; Fisher, John P; Material Science and Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Coronary artery bypass grafting (CABG) surgeries are a routine treatment for blockages in the coronary arteries. Autologous vessels from the patient are the gold standard of care, but they risk morbidity at the donor site, are restricted by availability, and yield high failure rates. Although commercially available synthetic grafts present an alternative conduit, they are characterized by high failure rates in small diameter vascular grafts, originating from inappropriate mechanical and biological properties. Tissue engineering endeavors have explored a plethora of materials for small diameter vascular grafts (< 6 mm) and have made significant contributions to the field; yet none have been able to provide a clinically feasible approach due to the complexity of native vessels. The work presented here is aimed at the development of a biohybrid vascular graft with spatially controllable, long-term heparin delivery. In the first part of this project, we establish a protocol for the decellularization of membranous tissues. We show that the abbreviated methodology effectively removes cellular content and preserves the extracellular matrix (ECM) in bovine pericardium (BP), with similar results in porcine urinary bladder matrix (UBM), as well. Next, we utilize decellularized bovine pericardium (dECM) and poly(propylene fumarate) (PPF) to construct a biohybrid (dECM+PPF) vascular graft. We demonstrate that the addition of PPF has beneficial impacts on the degradation of dECM. Further, we show that the dECM+PPF vascular graft has similar mechanical behavior to native vessels and supports growth and remodeling in vivo. Finally, we design and implement a heparin-loaded gelatin methacrylate (gelMA) interlayer as a technique for spatial and temporal control of drug delivery. The physical properties of gelMA can be altered with shadow masks during UV crosslinking to elicit unique release profiles. The masks lead to sustained release in dECM+PPF and induce distinct endothelial cell responses. The findings described in this dissertation detail the successful development of a biohybrid vascular graft that contains a spatially and temporally controllable heparin-delivery layer. This work provides an alternative approach for small diameter vascular grafts, as well as a drug delivery method that can be used to improve clinical outcomes in vascular grafts.Item Gradation of Porcine Bladder ECM in Hydrogels for Chronic Wound Treatment(2020) Allbritton-King, Jules; Kimicata, Megan; Fisher, JohnChronic, nonhealing wounds affect about 6.5 million individuals in the U.S., and often present as comorbidities of other prevalent conditions such as obesity and diabetes. Chronic wounds are characterized by a recurring inflammatory state without progression to the proliferation and remodeling stages of wound healing. Around $25 billion is spent annually on treatment of chronic wounds; however most traditional wound care approaches do not effectively encourage the physiological healing process. One emerging treatment option is extracellular matrix (ECM)-based wound dressings, which are composed of a network of proteins and other macromolecules that support and anchor cells within tissue. These dressings are typically composed of decellularized tissue derived from animal donors and provide a protein scaffold that mimics dermal ECM by facilitating cell adhesion. Most commercially available ECM-based dressings are dry, uniform sheets of ECM that provide a structural scaffold for cellular growth, but do not provide a physiologically relevant moisture balance or encourage cellular infiltration into the dressing as the wound heals. However, fibroblasts, which play a major role in wound healing, have been shown to migrate to regions of denser ECM concentrations, where they exhibit enhanced metabolic activity and proliferation. A UBM-based hydrogel will serve as an alternative wound dressing that will mitigate the issues with current ECM-based products. A hydrogel dressing offers a more physiologically relevant moisture balance to the site of the wound, while integrated structural cues will encourage fibroblast infiltration. Ultimately, this approach will increase the rate at which ulcers heal and prevent further deterioration of the wound site, in turn lessening the physical and financial burden on patients.