(6y) Unifying Engineering and Synthesis to Create Platform Biomaterials

Throughout my Ph.D. and postdoctoral studies, my overarching goal has been to help answer a difficult question: when we create new biomaterials, how do we ensure that they will work for our desired application? Indeed, predicting a priori if a biomaterial will function properly is a major challenge that the biomaterials community still faces today. For example, when developing drug-eluting reservoirs, how do we ensure that our system is not only biocompatible, but is also capable of maintaining the appropriate material properties throughout the course of our study? Alternatively, when studying specific disease states in vitro, how do we predict which biomaterials can be molded into better therapeutic models than those that already exist? Moreover, how do we ensure that our materials are both generally accessible and reproducible so that they can be studied broadly in academic and professional settings?

Leveraging principles from engineering and fundamental chemical synthesis, our research aims to answer these questions by employing a three-step process. First, we identify chemical space with untapped potential for biomaterials applications. Second, we design new biomaterials within these spaces that address unmet challenges. Finally, we synthesize these materials, ensuring that our systems are both scalable and reproducible. In following this process, our goal is to create platform biomaterials that not only can be used to treat and study specific diseases, but can also be broadly implemented within the biomaterials community.

Inspired by these questions, I focused my Ph.D. studies at MIT on integrating concepts from drug delivery, materials science, and synthetic chemistry to better understand how structure impacts function within non-viral delivery vectors for messenger RNA (mRNA) therapeutics. Therapeutic mRNAs could be used for a range of biomedical applications including genomic engineering, cancer immunotherapy, and protein replacement strategies. However, the serum instability of mRNAs and their limited ability to passively transfect cellular membranes limits their clinical potential. Lipid nanoparticles (LNPs) have emerged as an attractive non-viral delivery platform for improving the safety and potency of RNA therapeutics. Nevertheless, their complex molecular composition makes it difficult to understand which parameters ultimately impact the function of the LNP, thereby making it challenging to improve the efficacy and tolerability profiles of next-generation RNA delivery vectors. Towards this end, we have i. synthesized and purified rationally designed lipid materials of precise chemical structure, ii. formulated these materials into mRNA LNPs using microfluidic approaches, and iii. evaluated LNP potency and safety in vitro and in vivo as a function of the ionizable lipid chemical structure. Our lipids, which are actively being pursued as lead materials with pharmaceutical partners, ultimately represent robust RNA delivery vectors with high potency, low toxicity, and tunable biodistribution profiles without the need for targeting ligands or sequence modifications.

In my Postdoctoral research with Professor Bob Langer at MIT, we have developed scalable and modular hydrogels for biomedical applications. Specifically, we have created a class of mechanically- and kinetically-tunable hydrogels whose gelation occurs at physiologically relevant temperatures without the need for initiators, specialized laboratory equipment, or complex monomer synthesis. Our approach, which involves the self-assembly of a commercially available small molecule and a decagram-scalable polyethylene glycol derivative, ultimately affords hydrogels that are easy to fabricate on mutligram-scale. We are actively exploring several applications for our hydrogels including electrospraying strategies for stem cell recapitulation on implantable scaffolds, 3-dimensional printing models of cardiac valve disease, and islet entrapment for diabetes management. Additional efforts to explore the controlled release of therapeutics to the entrapped cell populations are also underway.

Teaching Interests: