Date(s) - 08/31/2020
3:00 pm - 4:00 pm
Virtual via Zoom
Nora Hlavac, Ph.D.
Combinatorial therapeutic approaches for addressing hallmarks of central nervous system injury
Central nervous system (CNS) traumas are among the most debilitating and costly injuries that people face. In addition, CNS injuries are pathologically convoluted and currently have no approved therapeutics on the market. Much work has been done to create biomaterial scaffolds for CNS, and while partial recovery has been achieved using these materials, research must progress beyond traditional strategies. My postdoctoral research has an overarching goal of engineering strategies that include advanced cellular and molecular cues to augment CNS regeneration when combined with natural-based biomaterial scaffolds.
First, we have investigated the combination of natural-based biomaterials with recombinant forms of chondroitinase ABC fused with galectin-3 (developed by the Hudalla lab), to target CNS glial scarring. Galectin-3 binds to galactosides in the extracellular matrix and specifically to chondroitin sulfate proteoglycans that make up glial scar tissue. The goal for using this fusion protein is to overcome the limitations of traditional chondroitinase treatment, which has a very short half-life and is not well retained at the injury site. We have combined the fusion proteins with triple-component hydrogels that are composed of modified hyaluronic acid, laminin and collagen I with mechanically-matched properties to spinal cord tissue. Our results have demonstrated biological efficacy of the fusion enzymes through increased release time and stabilized enzymatic activity when combined with biomaterial scaffolds.
In a separate project, we are focused on addressing the limitations of traditional stem cell transplantation in which there is often poor viability and host rejection of cells. Instead of transplanting cells, we are incorporating secretome (i.e., cellular secreted products) from adipose-derived stem cells (ASCs) into a decellularized nerve scaffold to augment the pro-regenerative effects for application in CNS injury. Efforts to increase the regenerative secretome products have included the use of exogenous electrical stimulation as well as various biochemical conditions to maximize ASC production of neural growths factors such as BDNF and wound healing factors such as VEGF. I will present our findings for the most optimal ASC secretome conditions and introduce our on-going research focusing on secretome encapsulation for sustained release from decellularized nerve scaffolds for eventual application in spinal cord injury.
Dr. Nora Hlavac is currently a postdoctoral associate in the J. Crayton Pruitt Family Department of Biomedical Engineering at University of Florida. She completed a BS in Bioengineering from Clemson University in 2014 and her PhD in Biomedical Engineering from Virginia Tech in 2018. During her PhD studies, Dr. Hlavac conducted research within the Center for Injury Biomechanics at Virginia Tech and taught graduate courses on cellular engineering and cellular physiology. She participated as a mentor in programs such as Multicultural Academic Opportunities Program (MAOP) to support the retention of diverse communities within research programs at Virginia Tech and Research Experience for Teachers (RET) to equip educators with research skills to teach in the K12 classroom. As a postdoctoral researcher, Dr. Hlavac now works on combinatorial therapies involving natural-based biomaterials for central nervous system injuries with collaborations in BME, College of Medicine, and Electrical and Computer Engineering. She continues to be dedicated to student mentorship and received the Leslie Williams Mentoring Award as part of 2019 UF Multidisciplinary Research Experience for Teachers (MRET).
Jorge Santiago, Ph.D.
Strategies for the Development of Clinically Relevant In Vitro Models of Human Tissues
The traditional paradigm used to develop drugs and treatments for neurological and musculoskeletal conditions relies in the use of two-dimensional (2D) monocultures of cells and animal models for in vivo studies. Although these approaches have contributed to the understanding of disease mechanisms and advanced promising therapies for debilitating conditions such as neuropathic pain and muscle wasting, both 2D cultures and animal models are limited in their efficacy at recapitulating human physiology. This talk will briefly introduce two approaches employed to engineer three-dimensional (3D) platforms for the study of physiologically relevant models of human tissue. In one of these applications, we leverage the micro-gravity environment found in the International Space Station to investigate accelerated degeneration of skeletal muscle as it has been experienced by astronauts. Our team is developing a muscle-on-a-chip, which consists of a scaled down engineered muscle with cells derived from patients, that can be functionally tested with electrical pulses and video recorded while in space. In another effort to provide accurate biophysical stimuli for patient-derived cells to interact in a 3D environment, we focus on producing tissue-specific hydrogels by optimizing methods to decellularize tissues from donor sources. Our recent work in the characterization of these natural biomaterials along with the implementation of 3D biofabrication strategies will be discussed. Lastly, the case will be made for future work in the development of 3D in vitro models of patient-specific human tissues as compelling alternatives for the screening of novel drugs and therapies as well as for the study of disease mechanisms.
Dr. Jorge Mojica-Santiago is currently a Postdoctoral Associate in the Department of Biomedical Engineering at the University of Florida. He received his BS degree in Mechanical Engineering at the University of Puerto Rico Mayaguez and completed his MS and PhD degrees in Biomedical Engineering from Cornell University. Dr. Mojica-Santiago became a Graduate School Dean’s Scholar under the Alfred P. Sloan Foundation in 2012 and was awarded an NSF Graduate Research Fellowship in 2013. He also actively mentored graduate peers and undergraduate students from underrepresented communities in STEM through the Society for Hispanic Professional Engineers (SHPE), coordinated a Technical Paper competition in the 2012 National SHPE Conference, and was elected Regional Graduate Representative in 2014. Before beginning his postdoctoral work, Dr. Mojica-Santiago supported summer programs for rising junior and senior high school students interested in engineering as an Assistant Program Coordinator of the Office of Diversity Programs in Cornell. His research interests include the development of tools to test potential treatments for debilitating conditions as well as the clinical translation of therapeutics for neuropathic ailments and musculoskeletal tissue diseases.