한빛사 인터뷰
1. Can you please briefly summarize the paper?
Before I explain this paper, I want to explain how I began doing this research. Metals are used commonly for dental, cardiovascular, and orthopedic applications, and traditional metals like titanium, cobalt-chromium, and stainless-steel alloys are still widely used in clinical settings due to their excellent biocompatibility and corrosion resistance. However, I did my Ph.D. in Dr. Jeremy L. Gilbert’s lab at Syracuse University (Dr. Gilbert is now at Clemson University), where we learned that even these biocompatible metals that are considered “bioinert” actually corrode due to many reasons, one of which is inflammation (i.e., inflammatory cell-induced corrosion, ICIC), that can potentially cause patient pain and implant failure. However, exactly why some patients suffer from ICIC while others do not when the same implants are used is still not exactly known.
Metal corrosion consists of oxidation and reduction reactions and during my Ph.D., I realized that reduction reactions are equally important in regulating biological/biochemical responses and cell-metal interactions. My Ph.D. work focused on galvanically coupling magnesium (Mg) with titanium (Ti) via sputtering to add a thin partial coating of Ti on the Mg particle surface, which spatially separated the oxidation of Mg metal and reduction reactions (which occurred on the Ti surface). The galvanic coupling of Mg and Ti significantly accelerated the corrosion rate by about 3 times compared to pure Mg, effectively eradicating osteosarcomas and mature E. Coli biofilms that cannot be killed using conventional antibiotics. Several important findings were derived from this work. First, Mg-Ti killed unwanted cells much more efficiently than pure Mg at lower metal particle concentrations. Second, I found that Mg and Mg-Ti could only kill cells in proximity (within 2 mm) and not harm cells further away. Lastly, I found that the cytotoxicity of Mg and Mg-Ti was not due to alkaline pH, which is usually attributed to being the primary source of in vitro cytotoxicity. Cells cultured in NaOH-adjusted cell culture media of the same pH level as those Mg and Mg-Ti were only killed after 24 hours, while those treated with Mg or Mg-Ti showed immediate reduction in viability after 1 hour of treatment. Therefore, we were able to conclude that at a high corrosion rate, some species were produced at the metal surface that killed cells effectively, quickly, but locally, which promised Mg-Ti with therapeutic potential therapy for cancer and orthopedic device-related infections.
With this research background, I became a postdoc and later an assistant professor at Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS). I was able to continue my research on Mg alloys under the supervision of Dr. Haobo Pan, but I had to align my research with goals that fit our center (our center name is Center for Human Tissue and Organ Degeneration), which is geared towards “regenerating degenerated tissues.” Mg alloys are biodegradable metals extensively studied in China and other countries due to many known advantages, one of which is that Mg ions released during oxidation are essential trace elements for the human body. Pure Mg is too brittle and degrades unpredictably and quickly, so most researchers studying Mg alloys are focused on improving the metal with different alloying, coating, and other surface fabrication techniques to increase the corrosion resistance and improve the biocompatibility of Mg alloys. While all researchers knew that Mg alloys are extremely biocompatible and even beneficial to bone regeneration if the Mg corrodes at a low-moderate rate, I wanted to systematically investigate exactly why and specifically how reduction reactions play a role concomitantly with Mg ions released at the Mg surface due to oxidation.
This paper I published in Bioactive Materials provides some novel insights, especially the biological mechanisms Mg corrosion affects, which some have never been, as far as I am aware, reported by other researchers who study Mg alloys. First, one of the most significant findings was that Mg at low-moderate corrosion could enhance cell proliferation by down-regulating intracellular ROS. However, this was not the case when cells were cultured in a simulated inflammatory environment (i.e., H2O2 present), where the total intracellular ROS levels actually increased, which did not increase nor decrease the cell proliferation. I was also able to measure in vivo ROS after subcutaneously implanting pure Mg rods immediately after the surgery up to 1-2 days, and in vivo ROS signal was only detected when pure Mg rod was present, meaning that Mg is the source producing ROS. Second, Mg regulated a key gene HIF1α over time and many signaling pathways, among which was PI3K/Akt/mTOR, known to regulate cell proliferation and differentiation. Mg also enriched many ROS-related pathways, such as mitophagy, cell cycle, and oxidative phosphorylation. In vivo Mg implantation also supported that HIF1α expression is significantly affected by Mg, where HIF1α expression did not really change over time for the control group (blank group without any treatment) but HIF1α expression for the Mg group was significantly up-regulated or down-regulated relative to the control group over time. β-catenin expression follows the same temporal regulation over time for the Mg group in vivo, showing significant up-regulation early on at 2 weeks and then significant down-regulation at a later time (4 and 8 weeks), where β-catenin is considered to be upstream gene in the Wnt/β-catenin signaling pathway, initiating osteogenesis. In conclusion, we should give more spotlight to reduction reactions, which affect cells and the microenvironment differently over time, depending on the Mg corrosion rate amongst many factors. In the future, we should further investigate how Mg alloys regulate cells and the microenvironment in pathological conditions, which are skewed in terms of pH, oxidative stress, inflammation, and so on, which will affect how Mg alloys interact with cells.
2. Can you please tell us the main difficulties you had in the laboratory work and how you overcame them?
The main difficulty I faced while doing research in China was the language barrier. I could not speak Chinese, which prevented me from working with other lab members as a team. I could not readily exchange ideas and engage in in-depth discussions with others, which made me feel isolated. However, I used this opportunity to develop my independence, constructing my research ideas and experimental designs, and leading and conducting research projects. Leadership and independence are indispensable qualities in becoming a professor and a PI, so I value this experience. During my four-year stay in China, I also learned some Chinese and was able to interact daily with my colleagues, who are now my good friends.
3. Please introduce your laboratory, university or organization to bio-researchers in Korea.
During my four years in China, I served as a postdoctoral researcher and later as an assistant professor/researcher under Dr. Haobo Pan, the director of the Human Tissue and Organ Degeneration Center at the Shenzhen Institute of Advanced Technology (SIAT), Chinese Academy of Sciences (CAS).
SIAT was jointly established in 2006 by CAS, the Shenzhen municipal government, and the Chinese University of Hong Kong. As one of the many research institutes directly affiliated with CAS—recognized as the world’s largest research organization with 106 institutes and two universities—SIAT emphasizes applied research and industrial innovation. The institute focuses on advancing fields such as nanomedicine, biotechnology, robotics, and electric vehicles, among others, resulting in the creation of 1,853 companies through its efforts.
Dr. Pan is also the founder and director of Shenzhen Healthemes Co. Ltd., a company dedicated to commercializing biomaterials. His primary research centers on developing bioglass-based materials to enhance bone healing and regeneration, addressing challenges such as diabetic-impaired bone healing, osteoporosis, and osteosarcoma-induced bone lesions. He is one of the leading researchers working on bioglass, where Dr. Pan’s lab integrates cutting-edge biomaterial design with investigations into the biological and biochemical mechanisms influenced by these materials, including their impact on signaling pathways. This dual focus not only facilitates product commercialization but also advances the scientific understanding of biomaterial interactions. While my research primarily focused on magnesium alloys, Dr. Pan’s expertise and research in bioglass-based materials complemented my work, as I was also interested in exploring how magnesium alloys impact the bone microenvironment.
4. Please tell us about your experiences and your thoughts related to research activities abroad.
Studying abroad is almost always a positive experience for expanding your research ideas, knowledge, and skills. Different countries, universities, and labs cultivate their own unique research methods/approaches and ethics, often reflecting the major health and clinical challenges specific to their regions. Research is a frontier work that thrives on global collaboration, so I strongly advocate for studying abroad. In fact, I would even suggest that studying abroad is an essential step for to-be professors and researchers to develop well-rounded perspectives they can share when they return to their home countries.
In terms of research, degradable metals like magnesium alloys are quite popular in China than elsewhere, with about 45.49% of Mg-based papers published from China, followed by only 7.68% from India and 4.91% from the United States [this data is from Yang et al. J. Magnes. Alloy. 2022]. The popularity of Mg research may have been one of the reasons why I got so much support doing my Mg alloy research in China, where I received Research Fund for International Young Scientists from National Natural Science Foundation of China (NSFC), with a project titled, "Systematic Investigation of Metal-Cell Interactions of Mg Alloys for Bone Regeneration and Bone Tumor Therapy" (Grant No. 52250410340) in 2022, which led to the publication of my paper in Bioactive Materials. I personally think that I could not have received the NSFC grant for this topic if Mg metal is not a popular research area that is gaining so much attention in China. Therefore, considering what research topic is "hot" in that country is necessary to gain the financial and other support you need for your research.
5. Can you provide some advice for younger scientists who have plans to study abroad?
Studying abroad can be challenging because your overall experience depends not only on research performance but also on personal factors such as your ability to speak the language fluently, forming deep interpersonal relationships with colleagues, and overcoming nostalgia for family and friends back home. I believe that good research stems from a happy researcher. However, when you go abroad, many factors become uncertain, and their effects on your physical, mental, and emotional well-being can be unpredictable.
While decisions to study abroad often depend on external factors such as the accredited university and professor you will work with, the financial costs of studying abroad, and the career opportunities available afterward, I hope young scientists remember to prioritize their personal happiness. Ask yourself a simple question: Am I happy with this decision? When you are truly happy with your choice, you are more likely to stay motivated and willing to make the necessary sacrifices along the way. Ultimately, the achievements you attain will feel much more rewarding and fulfilling.
6. Future plan?
I have decided to resign from my position as an assistant professor at the Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, effective December 31, 2024. Starting January 2, 2025, I will begin a new role as a postdoctoral researcher at the University of Pennsylvania under Dr. Claudia Loebel. Although I deeply valued my experience in China, I have chosen to relocate back to the United States for personal reasons. I am especially excited to join Dr. Loebel’s lab, which focuses on understanding how the nascent matrix microenvironment influences cell and tissue functions. Using metabolic labeling techniques, her lab aims to develop engineered platforms for tissue repair and treatment.
My previous research on biomaterials highlighted the critical role and importance of the tissue microenvironment, an essential factor in determining the success and native performance of implants. Therefore, I believe that my future work in studying extracellular microenvironment (ECM)—combined with my past research experience on implants, bone regeneration, bone-related diseases, and orthopedic device-related infections—will equip me with the skills and knowledge to broaden my research scope. The transition aligns with my long-term research goal, which is designing personalized biomaterials that guide cell behavior and direct cell fate, tailored to the unique tissue microenvironment of each patient, varied due to aging and/or different pathological conditions.
7. Do you have anything else that you would like to tell Korean scientists and students?
Research can be frustrating 99% of the time, with just 1% satisfaction. Yet, research happens when we do not give up. I struggled a lot—perhaps more than others—as I was trying to hold my career together while I got married, had two kids, and immigrated twice: to China and now back in the USA again. Balancing multiple roles in life is hard, as I am not only a researcher but also a mother. Being a good mother while striving to be a competitive researcher is incredibly difficult, and I still struggle now as my kids are still young. Sometimes, I need to prioritize one role over another, continuously juggling responsibilities to keep my life balanced. I feel extremely tired at the end of the day and aging at the speed of light, but also, at the end of the day, my research gives me the motivation to get up the next morning, and my kids make me laugh. I cannot imagine losing either because they are all essential to who I am now. So, let’s try to remember that we are imperfect, and it is okay to stay that way as long as we are striving for our growth and happiness.
I would also like to take this moment to thank my husband, Huiyu Shi, who gave me the infinite support and love I needed to flourish and carry on my research. I also want to thank my parents and parents-in-law for all the babysitting they did so I could focus on my work. Without family, this paper could not exist.
I also extend my deepest thanks to my life mentor, Dr. Jeremy L Gilbert, who laid my research foundation and taught me everything I know about metals, inspiring me to continue my work in China. I am also profoundly grateful to Dr. Haobo Pan for all his patience and understanding, which allowed me to achieve many milestones in his lab. A special thanks to Dr. Ping Du, my supervisor, colleague, and now friend, who helped me adjust to the new environment in China. She also taught me so many biology-related techniques and skills that enabled me to carry out my research. Finally, I want to thank Dr. Claudia Loebel, whom I met at the World Biomaterials Congress in 2024. She appreciated the research journey I took, understood all the bumps I faced on the road, and gave me a chance to learn and work in her lab. I hope to contribute and become a valuable member of her lab as I begin a new chapter at the University of Pennsylvania.
#Corrosion
# Magnesium Alloy
# Reduction Reactions
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