Education
Bachelor of Science in Engineering (BSE), Bioengineering, University of Pennsylvania, 2013
Masters of Science of Engineering (MSE), Bioengineering, University of Pennsylvania, 2014
Masters of Engineering (M.Eng), Biomedical Engineering, Rutgers University, 2018
PhD Candidate, Biomedical Engineering, Rutgers University
Research Interests
Drug Delivery, Stem Cell Therapy, Inflammation, Local Anesthetics
Research Summary
The goal of my work is to develop a multi-modal approach to target osteoarthritis (OA). Osteoarthritis is the leading cause of disability in adults in the US. There are an estimated 1 in 3 people between the ages of 18-65 have some form of arthritis, and OA is the most prevalent type. OA is a disease of the entire joint, not just a simple degenerative wear and tear. As in all forms of arthritis, inflammation plays an important role in OA, however the role is largely regulated by chemokines and cytokines. These pro-inflammatory factors help drive the production of proteolytic enzymes that are responsible for degrading the ECM. Therefore, treatments for OA focus on three main components: pain, inflammation, and regeneration. To target pain and inflammation, NSAIDs and opioids are treatment options and are beneficial in the short term. However side effects, including kidney and gastrointestinal issues, as well as their addictive nature, make them ineffective for long term pain management. Local anesthetics (LA), on the other hand, are generally non-toxic, but their duration is short. Therefore, a sustained release LA system would help prolong pain mitigation effects without the negative side effects associated with NSAIDs and opioids.
Aside from pain, one of the key aspects of OA is inflammation. Mesenchymal stromal cells (MSC) are multipotent stem cells that can control multiple physiological functions via paracrine secretion. However, LAs can affect MSC viability and function. The Yarmush lab previously has shown that in the presence of LAs, MSC secretion and therefore, anti-inflammatory function, is altered. Therefore, an improved method of co-administration of LA and MSCs is necessary.
We have developed a sustained release LA delivery model that could enable the co-administration of LA and MSC. Liposomes containing bupivacaine were encapsulated in an alginate matrix, which enables the sustained release of bupivacaine as compared to bupivacaine-containing liposomes alone. In vitro analysis indicated that using the construct compared to bolus bupivacaine increased MSC viability and cell secretion of prostaglandin E2 (PGE2), an anti-inflammatory cytokine, which indicates better anti-inflammatory properties and overall functionality.
Since the overall goal is to create a dual therapy, a method of stabilizing the cells at the injury site is necessary. Our lab has previously used alginate microspheres to encapsulate the cells to provide positional control. Moreover, our recent studies indicated that by encapsulating the MSC, the cells are protected from the LA. Therefore, higher doses of LA can be used in conjunction with eMSC in order to reach clinically relevant LA levels while still promoting eMSC viability and immunomodulatory secretion. These results indicate that the alginate encapsulation provides several therapeutic benefits including 1) limiting LA diffusion into the cell containing alginate microenvironment, and 2) positional control of MSC for a co-therapy with LA.
Awards & Honors
NIH Rutgers-UMDNJ Biotechnology Training Grant Fellowship
US Department of Education GAANN-Match Fellowship
Travel Scholarship to attend SACNAS 2018
First Place Poster Presenter at STEMcosR
Publications
Davis, M.S., Perez, X.I., Marrero-Berrios, I., Maguire, T., Rabolli, C., Weinberg, J., Manchikalapati, D., SchianodiCola, J., Kamath, H., Schloss, R., Yarmush, J., (2018) “Alginate Encapsulation Protects MSC from Bupivacaine Functional Depression”. J Inflammation Research. 2019(12):87-97. https://www.dovepress.com/alginate-encapsulation-for-bupivacaine-deliver...
Davis, M.S., Marrero-Berrios, I., Perez, X.I., Maguire, T., Weinberg, J., Manchikalapati, D., SchianodiCola, J., Kamath, H., Schloss, R., Yarmush, J. (2017) “Alginate-Liposomal Construct for Bupivacaine Delivery and MSC Function Regulation.” Drug Delivery and Translational Medicine. 8(1):226-238; PMCID: PMC6218803 https://www.ncbi.nlm.nih.gov/pubmed/29204926
Maguire T, Davis M, Marrero-Berrios I, Zhu C, Gaughan C, Weinberg J, Manchikalapati D, SchianodiCola J, Kamath H, Schloss R, Yarmush J. (2016). “Control Release Anesthetics to Enable an Integrated Anesthetic-Mesenchymal Stromal Cell Therapeutic.” Int. J. Anesthesiology & Pain Medicine. 2(1:3) http://anaesthesia-painmedicine.imedpub.com/control-release-anesthetics-to-enable-an-integrated-anestheticmesenchymalstromal-cell-therapeutic.php?aid=9980
Cohen JE, Purcell BP, MacArthur JW Jr, Mu A, Shudo Y, Patel JB, Brusalis CM, Trubelja A, Fairman AS, Edwards BB, Davis MS, Hung G, Hiesinger W, Atluri P, Margulies KB, Burdick JA, Woo YJ. (2014) A bioengineered hydrogel system enables targeted and sustained intramyocardial delivery of neuregulin, activating the cardiomyocyte cell cycle and enhancing ventricular function in a murine model of ischemic cardiomyopathy. Circ Heart Fail. 7: 619-26. PMCID: PMC4157671. https://www.ncbi.nlm.nih.gov/pubmed/24902740
Representative Graduate Courses Taken
Bioengineering in the Biotechnology and Pharmaceutical Industries
Professional Preparedness in Biotechnology
Innovation and Entrepreneurship for Science and Technology
Nano- and Micro- Biointerfaces
Structure and Dynamics in Adult and Stem Cell Biology