(7av) Micro-/Nano-Fabrication and 3D-Bioprinting Technologies: An Engineering Approach Toward Translational Medicine

Despite tremendous research and progress in surgical, chemotherapeutic, and radiological interventions for cancer treatment, the eradication of cancer tumor remains a dream as cancer recurrence and subsequently, the overall life expectancy in cancer patients is only a few months. While most studies have focused on tumor function and biology, the contribution of tumor surrounding tissues on regulation and differentiation of cancer cells, cell migration, and disease progression have been either underestimated or ignored. Therefore, the behavior of tumors is often a reflection of complex physiological interactions among cells and extracellular matrixes (ECM) in response to a treatment in a 4-dimensional domain: 3-dimentional microenvironment and time. On the other hand, the bench-to-bedside translation of novel therapeutic agents and controlled delivery systems is highly challenging due to lack of trustable pre-clinical (i.e. in vitro and in vivo) evidence as the performance of drug at the site of disease may be highly variable, making standardization and benchmarking are difficult and costly practices.

The advances that will take place over the next few years in the field of drug delivery and tissue engineering are very difficult to predict. However, based on the aforementioned problems, the time is right to construct an inexpensive, more efficient, and innovative in vitro screening model that can more accurately predict the in vivo (i.e. in human) pharmacokinetics and pharmacodynamics of new therapeutics and drug delivery systems. The recent advances in micro-/nano fabrication technologies and 3D-bioprinting have opened a new avenue for the miniaturized design and construction of organ tissue models with versatile biological functions toward personalized medicine.

As an educator and scientist, my research interests lie at the interface of drug delivery and tissue engineering, where the development and integration of advanced biomaterials with the state-of-art engineering technologies create functional tissue constructs helping to understand disease, develop therapies, and screen drugs for a range of medical applications. I intend to integrate my chemical and biomedical experience with other expertise such as biology and medicine in a multidisciplinary research team for addressing unsolved clinical problems and developing translational technologies. To achieve this goal, my research will specifically focus on the following major directions:

1) Engineering 3D-tissue construct using emerging technologies (i.e. micro-/nano fabrication and 3D-bioprinting) with controlled architectures.

2) Developing a cost-effective and reliable in vitro model for (a) high throughput screening of drugs, (b) testing new drug delivery systems and reducing the number of pre-clinical animal models, and (c) exploring cancer behavior via a well-designed in vitro model.

3) Developing novel advanced biomaterials with controlled physicochemical properties for on-demand drug delivery and tissue regenerative purposes.

In my graduate and post-doctoral research, I have mainly focused on the smart biomaterial synthesis and characterization and micro-/nano-fabrication and 3D-bioprinting as emerging technologies for drug delivery and tissue engineering. My Ph.D. research has focused on the synthesis of smart block copolymers and development of smart nanomaterials for the co-encapsulation of anticancer drugs and nucleic acids, where the new delivery system could sensibly respond to intracellular triggers and release cargoes at desired sub-cellular compartments. In addition, I developed a novel injectable, self-crosslinked, and antibacterial hydrogel/core-shell microparticle composite system for dual-agent treatment of metastasis breast cancer. The hydrogel provided an additional diffusion barrier against anticancer agents loaded into double-walled microspheres and confined their premature release. We also demonstrated that the hydrogel could be utilized as a versatile tool for retaining microparticles in a tumor resected cavity during injection after debulking surgery and preventing surgical site infection due to its inherent antibacterial properties. In another project, the core-shell microparticles (loaded with plasmid DNA nanoparticles and a protein-protein interaction inhibitor (a new small molecule drug)) were successfully fabricated and employed against liver cancer cells in a 3-D tumor construct.

In my Postdoctoral research, our multi-disciplinary team comprising of engineers, biologists, and clinicians have developed a unique biocompatible composite bioink for 3D-bioprinting elastomeric scaffolds. Specifically, we have developed a versatile 3D-bioprinted cell-laden composite hydrogel for the fabrication of a well-designed skin tissue construct. Additional efforts are exploring the use of 3D bioprinting technique for the rapid fabrication of micro-patterned 3D-vascular network tissue model for in vitro drug screening. My research has generated 10 manuscripts in refereed journals and more than 10 publications in prestigious international conferences.

I have also actively participated in mentoring and training 12 undergraduate students and junior research staffs and coordinated research activities in the biomedical lab over the past 5 years.

Education:

• Postdoctoral Research Fellow: National University of Singapore; 01/2017-present.

Postdoctoral Project: “3D-printing of Biomimetic Skins for Skin Care Products Testing Using the Electro-hydrodynamic Jetting (e-jetting) Technique”.

• Doctor of Philosophy (Ph.D.): Chemical and Biomolecular Engineering; National University of Singapore, 2011-2016.

Ph.D. Dissertation: “Fabrication of Micro-/nanoparticulate Carriers for Dual-agent (drug and gene) Cancer Therapy”.

Co-supervised by Professor Chi-Hwa Wang (National University of Singapore) and Professor M.P. Srinivasan (RMIT, Australia).

Grant writing:

• Contributed to the writing of research proposals: for instance, National Medical Research Council, 2013, 2014, 2015, Singapore Cancer Society, 2014, BIGHEART Grant Full Proposal, 2017.

Selected Journal Publications:

• Pooya Davoodi, F. Feng, Q. Xu, W.C. Yan, Y.W. Tong, M.P. Srinivasan, V. K. Sharma, C.H. Wang. Coaxial Electrohydrodynamic Atomization: Microparticles for Drug Delivery Applications. Journal of Controlled Release, 205, 2015, 70-82.
• J. Xie, J. Jiang, Pooya Davoodi, M.P. Srinivasan, C.H. Wang. Electrohydrodynamic atomization: Two Decades of Effort for Producing and Processing Micro-/nanoparticulate Materials. Chemical Engineering Science, 125, 2015, 32-57.
• Pooya Davoodi, M.P. Srinivasan, C.H. Wang. Synthesis of Intracellular Reduction-Sensitive Amphiphilic polyethyleneimine and poly(ε-caprolactone) Graft Copolymer for On-demand Release of Doxorubicin and p53 plasmid DNA. Acta Biomaterialia 2016; 39: 79-93.
• W.C. Yan, Pooya Davoodi, Y.W. Tong, C.H. Wang. Computational Study of Core-shell Droplet Formation in Coaxial Electrohydrodynamic Atomization Process. AIChE Journal 2016; 62(12): 4259-4276.
• Pooya Davoodi, W.C. Ng, W.C. Yan, M.P. Srinivasan, C.H. Wang. Double-walled Microparticles-embedded Self-crosslinked, Injectable, and Anti-bacterial Hydrogel for Controlled and Sustained Release of Chemotherapeutic Agents. ACS Applied Materials & Interfaces 2016; 8(35): 22785-800.
• Y. Cui, Q. Xu, Pooya Davoodi, D. Wang, C.H. Wang. Enhanced intracellular delivery and controlled drug release of magnetic PLGA nanoparticles modified with transferrin. Acta Pharmacologica Sinica, 2017; 38(6):943-953.
• Pooya Davoodi, M.P. Srinivasan, C.H. Wang. Effective Co-delivery of Nutlin-3a and p53 genes via Core-shell Microparticles for Disruption of MDM2-p53 Interaction and Reactivation of p53 in Hepatocellular Carcinoma. Journal of Materials Chemistry B, 2017; DOI: 10.1039/C7TB00481H.

Teaching Interests:

My objective as a teacher is to motivate students to develop their thinking abilities, learning interests, and problem-solving capability. In particular, working as a teaching assistant, grader, and moderator of clinic sessions, I have tried to establish a learner-centered environment in the classroom where I focus on creating a dialogue with the students, asking them to raise questions and helping discover answers step-by-step by themselves. I believe a good teacher should not only prepare an interesting course plan and materials that encourage students for learning, he must consider the interconnection between student’s knowledge, learning abilities, and accompanying theoretical concepts with practical examples such that students enjoy from what they learn in a class. I like to accompany my teaching materials with my own research background where students can find the applications of their knowledge in reality. Due to establishing a strong academic background in chemical engineering core modules during my undergraduate, master and PhD study, the courses that I would enjoy teaching include Heat and Mass Transfer, Unit Operation, and Separation processes at undergraduate level. Moreover, I have gained valuable experience in biomaterials preparation and processing during my PhD and would like to actively participate in developing new courses on the preparation and processing of innovative biomaterials and micro-/nanofabrication of biomedical devices for undergraduate/graduate students, where they will be introduced to the new aspects of chemical engineering science.