About

Aaron D. Bennett, MD, is an Assistant Professor of Clinical Pediatrics specializing in Gastroenterology, Hepatology, and Nutrition at the Children's Hospital of Philadelphia. He is part of the Division of GI, Hepatology and Nutrition within the Department of Pediatrics at the University of Pennsylvania's Perelman School of Medicine. Dr. Bennett completed his BS in Biology and Health Sociology at Brandeis University in 2011, earned his MD from Temple University School of Medicine in 2017, and obtained an MS in Health Policy Research from the University of Pennsylvania School of Medicine in 2024. His professional focus includes pediatric gastrointestinal and liver diseases, with research contributions in areas such as medical communication, health disparities, and genetic factors influencing liver transplantation outcomes.

Research topics

• Biology
• Chemistry
• Materials science
• Biochemistry
• Physics
• Biophysics
• Composite material
• Nanotechnology
• Combinatorial chemistry
• Chromatography
• Internal medicine
• Medicine
• Cell biology

Selected publications

• Biomechanical Impact of Pathogenic MYBPC3 Truncation Variant Revealed by Dynamically Tuning In Vitro Afterload

  Journal of Cardiovascular Translational Research · 2023 · 5 citations

  • Cell biology
  • Internal medicine
  • Chemistry
  PublisherOA PDFDOI

• DNA nanotechnology for nucleic acid analysis: sensing of nucleic acids with DNA junction-probes

  The Analyst · 2023 · 6 citations

  • Nanotechnology
  • Chemistry
  • Combinatorial chemistry

  DNA nanotechnology deals with the design of non-naturally occurring DNA nanostructures that can be used in biotechnology, medicine, and diagnostics. In this study, we introduced a nucleic acid five-way junction (5WJ) structure for direct electrochemical analysis of full-length biological RNAs. To the best of our knowledge, this is the first report on the interrogation of such long nucleic acid sequences by hybridization probes attached to a solid support. A hairpin-shaped electrode-bound oligonucleotide hybridizes with three adaptor strands, one of which is labeled with methylene blue (MB). The four strands are combined into a 5WJ structure only in the presence of specific DNA or RNA analytes. Upon interrogation of a full-size 16S rRNA in the total RNA sample, the electrode-bound MB-labeled 5WJ association produces a higher signal-to-noise ratio than electrochemical nucleic acid biosensors of alternative design. This advantage was attributed to the favorable geometry on the 5WJ nanostructure formed on the electrode's surface. The 5WJ biosensor is a cost-efficient alternative to the traditional electrochemical biosensors for the analysis of nucleic acids due to the universal nature of both the electrode-bound and MB-labeled DNA components.

  PublisherOA PDFDOI

• Magnetic field tuning of mechanical properties of ultrasoft PDMS-based magnetorheological elastomers for biological applications

  Multifunctional Materials · 2021 · 8 citations

  • Materials science
  • Composite material
  • Physics

  . Single fit parameter equations are presented that capture the tunability of the moduli and surface roughness as a function of CIP volume fraction and magnetic field strength. These magnetic field-induced changes in the mechanical moduli and surface roughness of MREs are key parameters for biological applications.

  PublisherOA PDFDOI

• Cardiac Microtissue Platform with Dynamically Tunable Afterload Control to Show Contractile Reserve and Pathologic Hypertrophy

  Journal of Cardiac Failure · 2019-08-01

  article
  PublisherDOI

• Tunable and Reversible Substrate Stiffness Reveals a Dynamic Mechanosensitivity of Cardiomyocytes

  ACS Applied Materials & Interfaces · 2019-05-10 · 86 citations

  article

  New directions in material applications have allowed for the fresh insight into the coordination of biophysical cues and regulators. Although the role of the mechanical microenvironment on cell responses and mechanics is often studied, most analyses only consider static environments and behavior, however, cells and tissues are themselves dynamic materials that adapt in myriad ways to alterations in their environment. Here, we introduce an approach, through the addition of magnetic inclusions into a soft poly(dimethylsiloxane) elastomer, to fabricate a substrate that can be stiffened nearly instantaneously in the presence of cells through the use of a magnetic gradient to investigate short-term cellular responses to dynamic stiffening or softening. This substrate allows us to observe time-dependent changes, such as spreading, stress fiber formation, Yes-associated protein translocation, and sarcomere organization. The identification of temporal dynamic changes on a short time scale suggests that this technology can be more broadly applied to study targeted mechanisms of diverse biologic processes, including cell division, differentiation, tissue repair, pathological adaptations, and cell-death pathways. Our method provides a unique in vitro platform for studying the dynamic cell behavior by better mimicking more complex and realistic microenvironments. This platform will be amenable to future studies aimed at elucidating the mechanisms underlying mechanical sensing and signaling that influence cellular behaviors and interactions.

  PublisherDOI

• 3158 Sunitinib-Induced Cardiotoxicity in an Engineered Cardiac Microtissue Model

  Journal of Clinical and Translational Science · 2019-03-01

  articleOpen access

  OBJECTIVES/SPECIFIC AIMS: The aims of this study are threefold. Firstly, we are examining the effects of increased in vitro afterload (a proxy for hypertension) on human induced pluripotent stem cell cardiomyocyte (hiPSC-CM) response to sunitinib in a durable and dynamic cardiac microtissue culture system. Secondly, we are exploring effects of repeat exposure and recovery of both sunitinib and afterload throughout the lifetime of the hiPSC-CM microtissue. Finally, we are assessing methods to prevent and treat sunitinib induced cardiotoxicity. Primary outcomes for this study are commonly utilized metrics of cardiotoxicity: degree of caspase activation, electrophysiology benchmarks for minimum voltage threshold and maximum capture rate, and microtissue force generation. METHODS/STUDY POPULATION: HiPSC-CMs are cultured and matured as 3D cardiac microtissues (CMTs) on a microtissue array. After maturation, cells are exposed to sunitinib doses of 0µM, 0.5µM, 1µM or 5µM for 12 hours. Concurrently with sunitinib dosing, increases in microtissue array stiffness are created with application of an external magnetic field. Afterload spring constants are fixed at pre-determined physiologic values ranging from 0.5µN/µm, to 5µN/µm. For Aim 1: Half of the CMTs are harvested at 8 hours after sunitinib dosing to conduct the caspase 3/7 assay, and the remainder are examined for 3 days following drug exposure to track temporal changes in electrophysiology and force generation. For Aim 2: After CMT maturation, 12-hour exposures to sunitinib are repeated three times at a fixed dose, with doses separated by one week. Concurrently with sunitinib dosing, increases or decreases in microtissue stiffness are created by changing the strength of an applied external magnetic field to create “ramp up” or “ramp down” stiffness conditions. Caspase assay and contractility metrics are measured at each timepoint. For Aim 3: Experimental conditions are conducted as described in Aim 1. Prior to the introduction of sunitinib, either carvedilol or an AMP-kinase activator is added to the CMT culture media at physiologic concentrations. Primary outcomes are examined as in Aim 1. RESULTS/ANTICIPATED RESULTS: Aim 1: We hypothesize that increases in microtissue afterload, synchronized with sunitinib exposure will augment sunitinib toxicity in cardiomyocytes resulting in elevations of caspase 3/7 activity and minimum voltage capture as well as decreases in maximum capture rate and maximum force generation. Aim 2: We hypothesize that repeat exposures to both sunitinib and to increases in afterload will augment sunitinib toxicity in CMTs via the primary outcomes mentioned in Aim 1. Additionally, we hypothesize that decreases in afterload will decrease effective sunitinib toxicity in CMTs via the primary outcomes mentioned in Aim 1. Aim 3: We hypothesize that exposure to an AMP-kinase activator but not carvedilol will decrease the effects of sunitinib toxicity in CMTs via the primary outcomes mentioned in Aim 1. DISCUSSION/SIGNIFICANCE OF IMPACT: The use of small molecule, targeted chemotherapeutic agents is increasingly common. Many of these agents cause cardiotoxic side effects, the mechanisms of which are incompletely understood. Our lab has developed a novel 3D tissue engineering platform capable of supporting durable in vitro cardiac microtissues that experience dynamic alterations in their biomechanical load. By using this platform to examine the cardiotoxic effects of sunitinib, insight into treatment and prevention of this common problem will be developed.

  PublisherOA PDFDOI

• Abstract 756: Sunitinib-Induced Cardiotoxicity in an Engineered Cardiac Microtissue Model With Dynamically Tunable Afterload

  Circulation Research · 2019-08-02 · 1 citations

  article

  Introduction: Anti-angiogenic tyrosine kinase inhibitors (TKIs) have efficacy against many solid neoplasms. Unfortunately, their on- and off-target effects frequently cause hypertension (HTN) and heart failure. Nearly all cases of cardiac dysfunction are associated with HTN, but the mechanism for this association is unclear. Aims: We have developed a novel in vitro 3D tissue engineering platform that uses a magnetically tunable elastomer to create dynamic alterations in afterload felt by cardiac microtissues. We are using this platform to examine the impact of increased in vitro afterload (a proxy for HTN) on cardiotoxicity of the TKI sunitinib. Hypotheses: 1) Increased afterload augments sunitinib-induced cardiotoxicity 2) Repeat exposures to sunitinib and increased afterload will further augment this toxicity. Methods: Human induced pluripotent stem cell cardiomyocytes (96%) and human cardiac fibroblasts (4%) from a commercial vendor (NCardia, Inc.) were allowed to self-assemble and form cardiac microtissues. Microtissues were exposed to sunitinib (0μM-10μM) at differing levels of afterload for a minimum of 8 hours. After a washout period, tissues were either harvested for analysis or exposures to sunitinib and afterload were repeated. Outcomes measured after each drug exposure included caspase activation, contractile ability, and force generation. Results: The applied magnetic field produced increases in afterload from 0.509±0.032 to 0.698±0.031 μN/μm. At 36 hours after exposure to supratherapeutic concentrations of sunitinib, recovery of contractile function as measured by force generation of microtissues was greater under soft afterload conditions compared with stiff afterload conditions (2.52μN soft vs 1.16μN stiff). Conclusion: Our platform creates dynamic alterations in afterload in engineered cardiac microtissues. Use of this versatile platform to examine the cardiotoxic effects of sunitinib has given promising initial results. Future studies examining removal/application of afterload, repeat exposures to sunitinib, and exposure to cardioprotective drugs will allow for insight into the mechanisms, treatment, and prevention of sunitinib-induced cardiotoxicity.

  PublisherDOI

• Measuring Contact Mechanics Deformations Using DIC through a Transparent Medium

  Experimental Mechanics · 2017-07-27 · 10 citations

  article
  PublisherDOI

• Contact Measurements of Randomly Rough Surfaces

  Tribology Letters · 2017-09-02 · 49 citations

  article1st authorCorresponding
  PublisherDOI

• Contact and Deformation of Randomly Rough Surfaces with Varying Root-Mean-Square Gradient

  Tribology Letters · 2017-11-02 · 32 citations

  article
  PublisherDOI

Frequent coauthors

• W. Gregory Sawyer

  Moffitt Cancer Center

  14 shared

• Thomas E. Angelini

  University of Florida

  13 shared

• Kyle D. Schulze

  Auburn University

  11 shared

• Elise A. Corbin

  9 shared

• Kathryn L. Harris

  7 shared

• Alexia Vite

  University of Pennsylvania

  6 shared

• Angela A. Pitenis

  University of California, Santa Barbara

  6 shared

• Juan Manuel Urueña

  University of California, Santa Barbara

  6 shared

Labs

• Aaron D. Bennett LabPI

Education

• B.S., Biology and Health Sociology

  Brandeis University

  2011

• M.D.

  Temple University School of Medicine

  2017

• M.S., Health Policy Research

  University of Pennsylvania School of Medicine

  2024