(6hg) Zwitterionic Polymeric Platforms for Biologic Drug Delivery and Tissue Engineering

Research Interests:

Biologic products as therapeutics and biocompatible substitutes for tissue engineering are becoming prominent in the new era. However, both face similar fundamental challenges: undesired immunological responses and foreign body reactions, leading to complications. Polymer-based materials possess great potentials for tackling these problems as they have diverse chemical functionalities, adjustable mechanical properties, and tunable applicational features. Many studies have been conducted to provide potential solutions, but quite often as one problem is resolved, another one emerges. Therefore, I am interested in developing bioinspired, super-hydrophilic zwitterionic materials to tackle the roots of these problems. Zwitterionic materials have demonstrated their vast capabilities for medical applications as they (1) provide a hydration layer surrounding the materials to prevent non-specific interactions with the environment, (2) have water-loving properties which are compatible with living organisms, and (3) possess highly tunable features for various applications. Over five years of my Ph.D. research experiences, I have focused on and have developed interests in designing zwitterionic, polymeric platforms for biologic drug delivery and tissue engineering by hindering the recognition by the immune system. Beyond my current work on “shielding” foreign bodies, I believe that biomaterials-based proactive immunomodulation is an emerging field. My future research interests are as follows:

• Non-invasive systemic delivery systems of therapeutic biologics

Biologic products have always been an enticing idea due to their specificity towards an explicit disease. However, due to their susceptibility to environmental changes, protein drugs are usually delivered via intravenous injection to minimize loss. This often requires patients to spend a considerable amount of time in the hospital for unpleasant treatments. Therefore, non-invasive administration routes for large therapeutic biologics are highly desirable. Non-invasive systemic biological drug delivery via the pulmonary route has always been fantasized since the 1950s due to the large surface area of the lung for absorption. Yet, delivery of large proteins (molecular weight > 40 kDa) having an average bioavailability of only 1 to 5% via this route remains a primary constraint. In my current studies, we have developed a super-hydrophilic polymer-based delivery platform which (1) stabilizes proteins in the lung environment, (2) facilitates proteins in crossing the barrier, and (3) significantly enhances the pharmacokinetic properties of proteins. I envision that through this experience, I would like to further develop a platform for other non-invasive systemic deliveries of large proteins, such as oral delivery and transdermal delivery.

• Long-term implants with adjustable mechanical properties and no foreign body reaction

The field of tissue engineering has a different set of challenges to tackle. Developing tissue-mimicking grafts for successful integration with the host is one of the primary objectives for regenerative medicine. Many materials have been studied and utilized in the replacement of tissues with various properties. Nonetheless, similar to transplantations, these grafts often lose their functionality within a short period as a result of eliciting foreign body reaction towards the materials. In my current work, we have tackled the two significant issues of artificial implants - inappropriate mechanical properties and induced foreign body reactions. With sophisticated design, we are able to develop hydrogels (1) with adjustable mechanical properties for a wide range of applications, and (2) with no foreign body reactions after months of in vivo implantation. This exciting work brings promise to long-term implantation of artificial biomaterial for tissue substitutions. For one of my future directions, I aim to explore further the interaction between the materials and the cells, and the capabilities of these tunable hydrogels for various applications such as blood vessels and cartilage substitutes, with the aid of 3D printing techniques.

• Materials engineering for antigen-specific immunomodulation

One of the emerging fields that are developing alongside with new insights into immunology is the engineering of materials that can modulate the immune system. Materials are now being engineered to deliver antigens with better control of the interaction with critical immune cells in order to induce tolerance against specific antigens. Zwitterionic materials provide an interesting angle as nature-derived zwitterionic polysaccharides promote immunosuppressive CD8 T-cell responses. Integrating with our vast experience with the nature of zwitterionic materials, I would like to develop new materials that can (1) prevent undesired interactions with the host immune system, and (2) proactively induce tolerance towards proteins with high immunogenicity. With the fundamental studies of how new zwitterionic materials stimulate the immunosuppression of foreign therapeutics, these platforms can be further used for treating autoimmune diseases, such as Multiple sclerosis, Type 1 diabetes, and Rheumatoid arthritis.

Teaching Interests:

Coming from a life science background, I have gained valuable teaching experiences through teaching undergraduate core courses in Chemical Engineering, including Mass and Energy Balance, Thermodynamics, Quantum Mechanics, and Senior Capstone Project. My teaching is highly recognized throughout the department as I was awarded the “Award for Excellence in Chemical Engineering Graduate Student Teaching.” One of the most exciting classes I have experienced was the Special Senior Capstone Project. In a span of three quarters, I led a team of senior undergraduates to conduct experiments, develop business plans for medical devices, and participated in the “Hollomon Health Innovation Challenge” at the University of Washington. I have sharpened my mentorship, lecture designs, and project/experiment management skills through this great opportunity.

One of the major takeaways for me when I first encountered and tried to master the core courses of Chemical Engineering was the fact that all pieces of knowledge are applicable to various fundamental science studies, ranging from engineering to life sciences. I believe in teaching Thermodynamics, as well as Mass and Energy Balance, would be both engaging and informational for students wishing to enter engineering majors. Additionally, with my unique interdisciplinary background, I would like to design an introductory course at the interface between Cheimcal Engineering and Life Sciences. With my vast research experience, I would be excited to create graduate-level courses in emerging fields of Drug Delivery Systems, Nanomedicine, and Immunomodulatory Biomaterials.

I am also a firm believer in the education of communication. One of the major challenges that knowledgeable graduate students face is lacking the ability to express an idea clearly to different target groups. I wish to design lectures or create study groups focused on helping graduate students to write proposals, articles, and popular sciences. Besides conducting my independent research, I have enjoyed collaborating with researchers from various backgrounds. I recognized that it is the diversity that brings unique insights into the lives around us. I will embrace this principle in the classroom and lab in those I teach and facilitate discussions between groups of individuals with different backgrounds by nurturing alternative points of view, supporting open mindsets, and rewarding collaborations. Unlike basic sciences, such as Biology, Math, or Chemistry, Chemical Engineering is in the realm of applied sciences with engineering principles. Therefore, I aim to connect to high school students to provide more insights on “what is Chemical Engineering,” in hope to inspire next-generation chemical engineers. I wish to integrate this program with existing outreach efforts to encourage more kids to enter the STEM field and increase the diversity of perspectives for future challenges.