(4fj) Designing Advanced Biomaterials By Leveraging Advances in Macromolecular Engineering

The ability of synthetic polymers to reproduce the structure and functionality of biomacromolecules enabled by macromolecular engineering has continuously expand their application spectrum in medicine and biotechnology. My research interests lie in engineering the topological structure (e.g.branched, knotted or star) and functionality of polymers for different biomedical applications.. During my Ph.D., we constructed an efficient gene delivery vector based on a highly branched poly (β-amino ester)s. The gene transfection efficiency was much higher than their linear counterparts, and even higher than those commercial transfection reagents. This work was highlighted in Science, where editors describe the difficulty of efficient gene delivery to target cells as one of the many barriers to gene therapy and we “broke one barrier through the synthesis of a new class of delivery vector.” (P. Yeagle, Science 2016, 352, 1530). Recently, one gene therapy formulation based on this polymer has been granted Orphan Drug Designation by the FDA to treat recessive dystrophic epidermolysis bullosa and currently under Phase I Clincal Trials. I also identified a simple yet robust way of tailoring polymer architectures to diversify the chain growth directions during polymerization, by using multivinyl monomers, which are commercially available molecules. This method led to cyclized/knotted, branched polymer architectures (Y. Gao, Nat. Rev. Chem. 2020, 4, 194), which are similar to the structures of protein knots and the branched polysaccharides. The multifunctional polymers are photo-crosslinkable and can be readily used for 3D printing. We engineered this structure into tissue adhesive hydrogels, showing significantly enhanced tissue adhesive properties and low swelling ratios.

My postdoctoral work in the laboratory of Prof. Samir Mitratotri at Harvard University focuses on developing intravascularly injectable hemostatic agents. By functionalizing polymers with injury-targeting peptides, we created a highly biocompatible and efficient hemostasis agent that can be both administered systematically and halt the bleeding endovascularly. This design is of clinical significance, as it provides a pre-hospital treatment of internal, non-compressible bleeding, which is responsible for 90% of survivable mortalities in the military battlefield. Our animal bleeding experiments demonstrated that this agent can achieve a 97% reduction in blood loss. Moving forward, as an independent researcher, my goal is to build a research team that will focus on seeking macromolecular solutions for critical biomedical needs, including but not limited to drug delivery, hemostasis, and regenerative medicine. Two major application directions are: 1) de novo design of synthetic platelets as a way to address the platelet shortage, and 2) develop polymeric drug carriers that can cross the certain biological barriers more efficiently, which are of great interest for drug delivery.

Teaching interests:

During my Ph.D., I served as a teaching assistant for a graduate course entitled Tissue Engineering. I prepared and taught 3 lab modules (1 hour each) to demonstrate how to prepare polymer biomaterials, including polymer synthesis, nanoparticle fabrications, and hydrogel preparation. I am prepared to teach a broad range of undergraduate and graduate introductory and intermediate courses including but not limited to ‘Biomaterials’, ‘Nanomedicine’ and ‘Methods of Materials Characterization’. I have mentored 16 undergraduates and graduate students during my PhD study and Postdoctoral training. My education and academic experiences so far have left me with a strong interest in teaching. I look forward to an opportunity to continue my journey, both growing as a teacher and helping and benefiting from the next generation.

Selected Publications (see my Google Scholar or C.V. for a complete publication record. twitter@YongshenggGao):

1, Gao, Y., Sarode, A., Kokoroskos, N., Ukidve, A., Zhao, Z., Guo, S., Flaumenhaft, R., Gupta, A.S., Saillant, N. and Mitragotri, S., ‘A polymer-based systemic hemostatic agent.‘ Science Advances, 2020, 6(31), p.eaba0588.

2, Gao, Y., Zhou, D., Lyu, J., A. S., Xu, Q., Newland, B., Matyjaszewski, K., Tai. H., Wang, W. ‘Complex polymer architectures through free-radical polymerization of multivinyl monomers’. Nature Reviews Chemistry, 2020, 4, 194-212.

3, Gao, Y., Peng, K., Mitragotri. S., ‘Hydrogels from Chemical Crosslinking of Polymers via Step-growth Reactions and Their Clinical Impact’. Advanced Materials. 2021, Accepted.

4, Gao, Y., Newland, B., Zhou, D., Matyjaszewski, K., Wang, W. ‘Controlled Polymerization of Multivinyl Monomers: toward Single Chain Cyclized/Knotted Polymer Architecture’. Angewandte Chemie International Edition, 2017, 56(2), 450-460.

5, Liu, S.†, Gao, Y.†, Zhou, D.†, Zeng, M., Alshehri, F., Newland, B., Lyu, J., O’Keeffe-Ahern, J., Greiser, U., Guo, T., Zhang, F., Wang, W. ‘Highly branched poly(β-amino-ester) delivery of minicircle DNA for transfection of neurodegenerative disease-related cells’. Nature Communications, 2019, 10, 3307. (Equal Contribution)

6, Gao, Y., Huang, J.Y., O’Keeffe-Ahern, J., Cutlar, L., Zhou, D., Lin, F.H., Wang, W., ‘Highly Branched Poly(β-amino esters) for Non-Viral Gene Delivery: High Transfection Efficiency and Low Toxicity Achieved by Increasing Molecular Weight.” Biomacromolecules, 2016, 17(11), 3640-3647

7, Gao, Y., Zhou, D., Zhao, T., Wei, X., McMahon, S., O’Keeffe-Ahern, J., Wang, W., Greiser, U., Rodriguez, B., Wang, W. ‘Intramolecular Cyclization Dominating Homopolymerization of Multivinyl Monomers: toward Single Chain Cyclized/knotted Polymeric Nanoparticles’. Macromolecules, 2015, 48(19), 6882–6889

8, Gao,Y., Böhmera,V.,Zhou,D.,Zhao,T.,Wang,W., Paulusseb,J., ‘Main-chain Degradable Single-chain Cyclized Polymers as Gene Delivery Vectors’. Journal of Controlled Release, 2016, 244, 375– 383