(2ep) Charged Polymers and Granular Biomaterials for Biomedical Applications

Charged and granular biomaterials for biomedical applications

Overview: The overall goal of my research program is to lead a diverse and collaborative team to engineer charged polymer networks with electrochemical properties, which will be leveraged to develop in-vitro models and biomaterials for the development of therapeutics for treating cardiac and musculoskeletal diseases (Fig. 1).

In recent decades there has been increased interest in understanding how biomaterial properties affect cell activity. Such information is useful in the design of better therapeutics in tissue repair. Much emphasis has been placed on biomaterial mechanics and mechanotransduction, with significant progress made in the field, such as an understanding of the impact of viscoelasticity in cell fate, spreading, and migration. However, there has been less focus on understanding the importance of biomaterial charge on cell physiology, particularly in cells where the transmission of electrical signals due to changes in transmembrane potential plays a key role in cellular activity. Although, there have been significant studies designing conductive materials to bridge conduction on damaged or diseased tissue, there are limited studies on what happens at the interface of charged biomaterials and electroactive cells. Because many synthetic and natural polymers have charged groups and counter ions under physiological conditions, understanding their impact on cellular transmembrane potential and ion flux will be particularly important to developing better in vitro models and therapies. My lab will design and elucidate the impact of ionic polymers on cell activation and transmission of the electrical potential, while also leveraging this information in the development of therapies to treat diseases and injuries in conductive tissues. For example, in tissue engineering applications we will explore the modularity of charged granular hydrogels to control injectability and gelation kinetics, release bioactive molecules, and control degradation rates for cellular infiltration and remodeling. Electrochemical cues can also be exploited to develop sensing capabilities and to design better in vitro models to screen therapeutics. My previous and ongoing research has trained me to lead these efforts.

Previous and ongoing research

Engineering microgels and tissues to develop therapies for cardiac diseases (Postdoc): Under the mentorship of Professor Jason Burdick at the BioFrontiers Institute, I am learning new technologies related to the synthesis of modified natural polymers, microfluidic design, and in vitro and in vivo assays to fabricate and assess the impact of biomaterials (Fig. 2). Granular hydrogels consist of the jamming of hydrogel microparticles into solids that retain porosity for cellular invasion. There is a limited understanding of how particle shape (e.g., increased aspect ratios) affect granular hydrogel packing, injectability, cell invasion, and tissue reconstruction. Consistent with my overall lab goal, I am elucidating the impact of microgels of different aspect ratios on these granular material properties. Further, I am developing pacing approaches to activate cells in cardiomyocyte (CM) microtissues. Using brightfield and optical imaging analysis, I plan to assess the impact of charged polymers on CM electrical activity. I will incorporate charge polymers in 3D printed constructs to assess the impact on microtissues. This work will provide the background for many of the projects in my future group.

Development of injectable hydrogel for the treatment of ventricular arrhythmias (PhD): During my PhD training in Professor Elizabeth Cosgriff-Hernandez’s lab, I developed an injectable hydrogel that cured in-situ in cardiac veins to transform them into an electrode extension (Fig. 3). This technology aims to restore proper cardiac pacing using voltages below the pain threshold used in current defibrillation devices. This conductive hydrogel could reach the midmyocardium, allowing pacing of the heart in locations inaccessible to current pacing leads due to their limited flexibility and conformability. This approach could alter the landscape of cardiac rhythm management. Moreover, the greatest significance may not lay in the ability to defibrillate the heart more effectively, but rather to prevent re-entrant arrhythmias, which would be of significant benefit to the patient. This project was done in collaboration with Dr. Razavi and his skillful team at the Texas Heart Institute. The collaboration trained me in heart electrophysiology and in vivo animal models. A company was recently created to commercialize this technology. In addition, I learned from reversible chemistries for injectable hydrogels from my interactions with my co-advisor, Professor Rosales, and her research team. I am currently working on two additional manuscripts related to the degradation of PEG-derived hydrogels and the impact of hydrogel structures on the conductivity and mechanics of PEG-anionic hydrogels.

Polymeric microspheres for delivery of growth factors on porous bone scaffolds (PhD): In addition to my work in the cardiac space during my PhD, I worked in the development of an injectable bone graft for patients recovering from trauma or tumor resection. I fabricated porous microspheres of different sizes and pore diameters to encapsulate and control the release of growth factors (Fig. 4)—expanding my skillset in synthesis, drug delivery, controlled release, and engineering biomaterials for therapeutic applications.

Gold nanostructures and polyoxometalates for electrochemical applications (MS): Beyond biomaterials design, my initial research training was focused on catalysis for clean energy fuels. As part of my training in Professor Dumesic's lab I fabricated gold nanoparticles and gold nanotubes for selective hydrogen oxidation for fuel cell applications (Fig. 5). Selective CO oxidation in the hydrogen streams with low energy consumption was a challenge that we addressed using gold nanoparticles and polyoxometalates (POMs) in an aqueous solution. The resulting solution from the water gas shift reaction contained protons (H⁺) and electrons in the reduced POMs. We designed a fuel cell to generate electricity from this stored form of hydrogen. Then, I designed a second electrochemical cell that allowed us to transfer the hydrogen from the aqueous solution to an unsaturated hydrocarbon to facilitate transport and energy storage in other forms. I built foundational chemical engineering expertise in catalyst synthesis, nanostructures fabrication, materials characterization, and electrochemical cell design. This work was summarized in four papers published during my MS.

Teaching Interest

Teaching Philosophy: My teaching philosophy focuses on the holistic formation of individuals who identify and think critically about problems and provide solutions. The convergence of my experiences builds the four pillars of my teaching philosophy: 1) strong engineering fundamentals, 2) free thinking, 3) collaborative work, and 4) strong ethical values. This applies both to the classroom and the laboratory. To achieve this, the classroom and lab should be safe spaces where ideas are conceived, expressed, and discussed to create new knowledge and technologies and where students have freedom to fail.

My goal for students attending my courses is that they learn fundamental principles and apply them to look for creative solutions while also considering the broader impacts. For example, when teaching a drug delivery class, I can explain design criteria for the treatment of a given cancer, and then, based on those criteria, encourage students to think about what everyday materials fits the description. Through this process, students learn to assess the pros and cons of various delivery mechanisms, begin considering patient compliance and how cost affects patients’ access to medications. For students doing research, my goal is that they learn how to formulate questions, use literature to support those questions, and design experiments to test their hypotheses. Our worldview impacts all of these steps, and I intend to make students aware of this so they can identify and reduce unconscious biases. Lastly, because most students will do some project management throughout their eventual careers, I will incorporate activities to help them break their projects into tasks, identify the critical path, and complete key assignments during the semester.

Teaching interest : My broad training has equipped me with tools to teach different classes within the department. These include but are not limited to Biomaterials Design, Kinetics and Catalysis, Polymers Science and Engineering, Engineering Design, Process Manufacturing, and other core courses. In addition, I would like to develop courses in Drug Delivery, Conductive Biomaterials, and Pharmaceutical Operations, related to my research interest and engineering on pharmaceutical operations related to my experience in the industry, incorporating aspects of unit operations, product development, technology transfer, quality control, and regulatory issues. I am also interested in including moduli in my courses to address topics such as engineering ethics, project management tools, and health disparities. In addition, I would like to continue expanding relations with other Hispanic Service Institutions and Latin American Universities to foster scientific exchanges and potential collaborations across institutions.