(2gy) Skeletal Tissue Regeneration Using Physiochemical Cues

Bone fractures and defects are common yet acute medical conditions. Currently, the preferred routes for treatment are autografts and allografts. However, each of these courses of treatment have serious drawbacks. Hence, the approach of Tissue engineering is developed to mitigate both of these problems.

Challenges of the existing techniques of tissue engineering

Tissue engineering strategies, utilizing a combination of biomaterial scaffolds, stem cells or osteogenic cells and growth factors /osteogenic stimulating agents, has emerged as an important area to create artificially engineered bone grafts. Bone growth factors and osteogenic stimulating agents have a number of toxic side-effects including growth of ectopic bone fragments, increased risks of bone tumors etc. This demands an alternate method for inducing osteogenesis at the site of engineered tissue implantation. For instance, use of biophysical/biochemical cues can help in bone regeneration with a lower dose of growth factors or without the use of growth factors at all. Hence, I propose use of (1) Nitric oxide and (2) electrical stimulation in combination with bone tissue engineering to enable regeneration in critical sized defects.

Project 1: A biocompatible, biodegradable and antibacterial nitric oxide releasing scaffold for bone regeneration. Nitric oxide (NO) is a small molecule with strong bactericidal properties, the capacity to disperse biofilms, ability to induce endogenous vasodilator, reduce blood clotting, help in wound healing, promote angiogenesis and act as an anti-inflammatory agent. Studies have shown that NO has a lot of potential for helping in bone regeneration. However, role of NO releasing scaffolds in bone regeneration has not been studied at large. Only bone regeneration studies with NO have been done with use of NO releasing drugs ingested systemically (in vivo) or addition of NO donors to culture media (in vitro). The only studies involving NO releasing scaffolds have focused on the antibacterial properties instead of the osteogenic properties and often used non biocompatible and non-biodegradable materials for scaffold preparation like polyurethane. Moving forward, in this project, I propose designing and fabrication of a scaffold that produces sustained release of nitric oxide and has powerful osteogenic as well as antibacterial properties.

Project 2: Biodegradable, piezoelectric silk scaffold as tissue stimulator for bone regeneration. Electrical stimulation has been often used to treat bone fractures since it has the ability to accelerate bone regeneration. However, the electrical devices have certain limitations; while external stimulators are not very effective, implanted devices are often have toxic and non-degradable batteries, requiring invasive removal surgery after recovery. Piezoelectric materials are a group of “smart” materials in which electrical charge accumulates in the material in response to applied mechanical stress. Tissues such as bones are made up of piezoelectric material. So, when they’re under mechanical excitation, AC voltage sets up in whole body due to piezoelectric effect in the tissues. This activates cells, increases cell migration, ECM production. In this project, I propose designing and fabrication of a scaffold that is biocompatible, biodegradable and has a powerful piezoelectric property that can induce bone regeneration And, I propose use of silk for that purpose because silk is a known piezoelectric material which has not been studied in depth, especially for application of its piezoelectric properties in tissue engineering.

Project 3: Study of the effect of electrical stimulation from an implantable piezoelectric scaffold on the immune system. Electrical fields of different natures and magnitudes can react with the cells, ions in the body fluids and other biochemical factors to modulate different physiological processes. Physiological electric fields (EFs) are important factors that control and adjust the cellular and tissue homeostasis. These EFs can guide migration of cells, induce production of ECM, wound healing and tissue regeneration. For this reason, over the years, the use of external electrical stimulation to improve and enhance regeneration of tissues and healing of wounds has become a common practice. Interestingly, the use of different magnitudes of electrical fields have been established to achieve different biomedical purposes. For instance, EFs at lower voltages (10-100 mV) can be used for cell proliferation, migration and tissue regeneration applications. On the other hand, higher voltage electrical stimulations (above 1kV) can initiate electroporation, apoptosis, etc. which can be used to target and destroy diseased tissue like cancer.

Teaching Interests

Teaching philosophy My most effectual courses have been the ones that included interactive exercises and activities coupled with frequent testing on smaller parts of the syllabus to reinforce the learning of each part of the curriculum effectively. My favorite teachers had succeeded in instilling the passion for the subject they taught into me by making the learning process more involved while using a more direct and less stressful grading system so that most of my focus remained on learning. Hence, as a teacher, my main goal would be to create an interactive classroom environment rife with scientific discussions amongst the students in pairs/small groups as well as between the students and me. Lastly, in order to increase involved learning and critical thinking, I would also hold student presentations about twice a semester based on review of classical and current literature on the topics being covered in class. I look forward to honing my teaching skills based on these principles and developing my style further.

Experience I have had a very extensive teaching experience during my time as a PhD student at University of Connecticut that have exposed me to the challenges and rewards of being a good instructor. I have been a teaching assistant for the course, Enhanced Anatomy and Physiology which is a core subject offered by Dr. Xinnian Chen and Dr. Geoffrey Tanner in the Department of Physiology and Neurobiology. I have taught the lab component of the course since spring semester 2018. During my section lectures, I have always tried to stimulate small group discussions to engage students to think critically about the topic of discussion. I was also responsible for creating teaching materials and modeling the teaching style for at least one lab each semester. While creating teaching material, I always try to incorporate fun activities and exercises (like interactive matching activities, fill in the blanks, small group discussions etc.) that can get the students engaged and excited in the most mundane parts of theoretical learning. I also try to add in a few advanced exercises in my lectures that can motivate the students to think critically.

Coursework My training as a Chemical engineer and a Biomedical engineer has provided me a strong foundation in anatomy and physiology, material chemistry, mathematics and general engineering. Thus, I am prepared to teach all core undergraduate courses in Biomedical engineeing. I also intend to develop courses and electives based on my own research background to cater to the needs and wants of the department and students. These could include courses on electrically active biomaterials, tissue engineering, immune engineering, drug delivery, material engineering and fabrication techniques, etc. Since all these topics are constantly developing with new studies being published all the time, these courses will be combinations of classical lectures and literature reviews. The assignments in these courses will be based on conducting literature reviews, student presentations, project development, scientific proposal writing etc. My aim in this course would be to expose the students to important skills in conducting modern science like multidisciplinary collaborations, in-depth introspection etc.

Research Mentoring During my time as a master’s student at University of Georgia and as a PhD student at University of Connecticut, I have mentored around 14 undergraduate students in the lab. Most of these students were granted authorships or acknowledgements in my publications which helped them enormously in their own careers going forward. A lot of these students changed their career paths from med school to grad school or their majors from biology to engineering because of how inspiring and intriguing they found research with me. I was even nominated for the OUR (Office of Undergraduate Research) Mentorship awards in 2020 for my excellent mentorship of the undergraduate researchers.

Hence learning from my own mentoring experiences as well as from those that mentored me, I have come to understand that an open and collaborative research environment is essential for effective mentorship. In my own lab, I plan on implementing the same open and collaborative environment, where students would be encouraged to work with each other and rely on each other as well as me when it comes to solving issues they face in their projects. Furthermore, the nature of my research is highly multidisciplinary with required expertise from material scientists, engineers, cell and microbiologists, surgeons etc. So, my students would have to be highly collaborative with other professionals outside of the lab in order for them to carry out their projects smoothly. I expect this process to widen their awareness in sciences beyond their projects.