Oral Presentations

March 20, Ballroom, Curry Student Center

(9:30-9:45 AM) Utilizing a fiber-like platform to investigate the biophysical regulators of metastasis in the tumor microenvironment

Alex M. Hruska (1), Daniel F. Milano (5), Senthil K. Muthuswamy (4), and Anand R. Asthagiri (1,2,3) 1. Department of Bioengineering, 2. Chemical Engineering, and 3. Biology, Northeastern University, Boston, MA, USA. 4. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. 5. ImmunoGen, Inc., Waltham, MA, USA.

Metastatic cancers are responsible for 90 percent of all cancer related deaths, and the tumor microenvironment (TMEN) is a critical regulator of the metastatic dissemination of cancer cells. The TMEN is a dynamic microcosm which imposes a unique combination of chemical and physical cues to direct cell behavior, and recent studies have begun to uncover the important role of physical cues imposed by the extracellular matrix (ECM) in guiding cells out of the primary tumor. As observed in breast cancer, during metastasis protein fibers are re-organized to act as a highway cancer cells use to more efficiently escape the tumor, and the physical confinement imposed by the fibers alter gene expression to support distinct modes of invasive cell migration. By microcontact printing high aspect ratio ECM stripes onto flat substrates to mimic fibers, key aspects of confined fibrillar migration seen in vivo can be recapitulated. Different modes of cell migration are highly context dependent, thus micropatterned fiber-like surfaces represent a model system in which to study cell behavior in a more physiologically relevant environment. In this system, key regulators of cytoskeletal dynamics can be perturbed to reveal the biophysical underpinnings of invasive cell migration and metastasis.

(9:45-10:00 AM) Thermoresponsive Lipid Nanoparticles for Glioblastoma Chemotherapeutical Delivery

Mubashar Rehman(1,2,3), Di Shi(1), Thomas J. Webster(1), Asadullah Madni(2), and Ayesha Ihsan(3) 1. Department of Chemical Engineering, Northeastern University, Boston, MA 02115 2. Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan 3. Nanobiotechnology Group, National Institute of Biotechnology and Genetic Engineering, Faisalabad 38000, Pakistan

Lipid nanoparticles of solid and liquid lipids have been widely used for bioavailability enhancement and the sustained drug release of water insoluble drugs. We have previously shown that fine tuning of liquid content produces lipid mixtures that exhibit a melting point (MP) required for low temperature sensitive drug delivery. The objective of the present study was to comprehensively characterize the thermoresponsive nature of thermoresponsive lipid nanoparticles (TLN) in vitro for treating glioblastoma, the most aggressive form of brain cancer. For this, TLN were prepared by microemulsification of a lipid mixture, consisting of solid and liquid fatty acids, that show solid-liquid phase transition at 39˚C as shown by a change in viscosity and transmittance of light. Drug release studies were performed by the dialysis bag method and a modified electrochemical method for real time detection of thermoresponsive drug release at 37-39˚C. Next, cytotoxicity of the TLN were evaluated using an in vitro blood-brain barrier model. Results showed that unloaded TLN were non-toxic to endothelial and glioblastoma cells, whereas paclitaxel, a potent chemotherapeutic agent, loaded TLN were cytotoxic to glioblastoma cells after 24 hrs. In summary, this study shows much promise for the use of the presently fabricated TLN for treating glioblastoma.

(10:00-10:15 AM) CXCR4 binding peptide density targets triple negative breast cancer and hinders metastasis

Daxing Liu (1, 2), Craig McCarthy (1), Peng Guo (1, 3), Debra Auguste (1, 2, *)

1 Department of Chemical Engineering, Northeastern University, 360 Huntington Avenue, Boston, MA 02115
2 Department of Biomedical Engineering, the City College of New York. New York, New York 10031, United States.
3 Department of Surgery, Harvard Medical School and Boston Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115, United States
* Debra Auguste, 225 ISEC, Department of Chemicall Engineering, Northeastern University. Phone: +1-617-373-6243, email: d.auguste@northeastern.edu

CXCR4 is a key regulator in breast cancer metastasis; inhibition of CXCR4 via antibody targeting hinders cancer cell migration and reduces tumor burden in vivo. An acquired resistance to antibody therapy can limit the number of patients responsive to treatment and the long-term benefit. In this study, we synthesized liposomes bearing the D-enantiomer of a CXCR4 binding peptide DV1. Triple negative breast cancer (TNBC) cell lines (MDA-MB-231 and MDA-MB-436) exhibited stronger binding to liposomes functionalized with surface density of DV1 (24k molecule/um2) (L-DV1-24k) in vitro relative to non-neoplastic cells. An ex vivo study indicated that L-DV1-24k can discriminate between metastatic breast cancer cells and surrounding tissues, which means the early diagnosis characterization of the neoplastic transformed cancer site, as well as the circulating tumor cells. An in vivo lung metastatic model study indicated that L-DV1-24k can reverse the early metastatic trend of MDA MB 231-luc to lung by tracking CTC cells, early arrest and extravasation, and arising anoikis after administrating 2 times per week. Finally L-DV1-24k delayed MDA-MB-231 cells metastasis to lung for 3 weeks and kept 84.6% of tumor suppression rate for at least 31 days totally.

(10:15-10:30 AM) The Therapeutic Effect of Epigenetic Drug-encapsulating Lipid Nanoemulsions for Triple Negative Breast Cancer Cells

Bumjun Kim(1) Debra Auguste(1) 1. Department of Chemical Engineering , Northeastern University, Boston, MA, USA

Epigenetic therapy has emerged as an alternative to conventional chemotherapy due to its selectivity toward cancer cells that often present aberrant epigenetic patterns such as hypermethylation and histone deacetylation. However, the stability issues of epigenetic drugs have to be addressed for the efficient treatment. Herein, we present LPAR-targeted-lipid nanoemulsions(LNEs) encasulating two epigenetic drugs, Decitabine (DAC) and Panobinostat (PAN). Our result showed that the uptake of LNEs were dependent on the LPAR expression in triple negative breast cancer(TNBC) cell lines. DAC and PAN encapsulated LNEs(DAC/PAN-LNEs) effectively killed a variety of TNBC cell lines and suppressed the growth of breast cancer. We also investigated the working mechanism of DAC/PAN-LNEs in a molecular level. DAC/PAN-LNEs was effective in inhibiting the growth and the migration of mesenchymal breast cancer cells that overexpress mFOXM1 by restoring mCDH1/E-cadherin and suppressing mFOXM1 expression, while ineffective to epithelial breast cancer cells that inherently express low mFOXM1 and high mCDH1. Overall, we successfully LPAR-targeted LNEs encapsulating DAC and PAN that can selectively treat mCDH1(low)/mFOXM1(high) TNBC cell lines.

(10:30-10:45 AM) – COFFEE BREAK

(10:45-11:00 AM) A Cross–Reactive Array Based on Spectroscopically Encoded Polymers for the Classification of Biomolecules

Jessica Fitzgerald(1) and Hicham Fenniri(2)
(1)Department of Bioengineering and (2)Department of Chemical Engineering, Northeastern University, 360 Huntington Ave, Boston, MA, USA 02115-5000

The detection of biologically or environmentally significant analytes has employed sensor technology based on two major approaches. The first and most common sensing mechanism is based on the lock-and-key approach, where a strong and specific interaction between the sensory element and the analyte leads to a measurable signal. The second and more recent approach uses sensor arrays that emulate the mammalian gustatory or olfactory systems. The latter takes advantage of a series of physical and/or chemical changes resulting from specific or non-specific interactions of the analyte with each element of the sensor array. The collective changes in the array can then be extracted using multivariate data analysis, and plotted to show unique patterns for a given species. Earlier reports described cross-reactive sensor arrays (CRSA) with different sensory elements, including organometallic compounds, dyes, metalloporphyrins, nanoparticles, composite materials, enzymes, or lymphocytes. The changes registered by different types of CRSAs upon exposure to a given analyte include changes in electrical properties, acoustic waves, surface plasmon resonances, color, radioluminiscence, vapoluminiscence, and fluorescence. Herein we demonstrate a new approach to an artificial tongue based on the vibrational properties of spectroscopically encoded polymers, and its application to the classification of small and large biomolecules.

(11:00-11:15 AM) A Double Look: Using Biomaterials as an Art Platform

Tess Torregrosa, Abigail Koppes, and Ryan Koppes. Department of Chemical Engineering, Northeastern University, Boston, Mass., USA

Both the arts and STEM fields have always looked to push human thinking. At the intersection of art and STEM, artists have integrated new technology to be a medium and inspiration for their work. Some broad examples broad of exposing this intersection has been the through 3D printing, theater, and costume. This work will focus on two creations outside of Northeastern and a project from our lab, the Laboratory for Neuromodulation and Neuromuscular Repair (LNNR). Utilizing 3D printing, Amy Karle was able to create Regenerative Reliquary, a new media art, by printing stem cells and a scaffold to build bone. The play Orchids to Octopi by Melinda Lopez, commissioned by the National Institutes of Health, teaches the audience about evolution. Lastly, our idea of a nervous system inspired sculptural costume piece that incorporates our fiber technology normally used to stimulate neurons into wearable items. These projects involve both artists and scientists coming together to make something more than what either one could have achieved alone. Perhaps through art, we as scientists can bridge the gap between the STEM community and the public and excite a broader audience about new and novel ideas.

(11:15-11:30 AM) Injectable hydrogels for microfluidic applications

Aslihan Kazan, Seref Akay, Rabia Onbas, Ozlem Yesil-Celiktas
Department of Bioengineering, Faculty of Engineering, Ege University, 35100 Bornova-Izmir, Turkey

Injectable hydrogels are unique materials developed for diverse life science applications such as drug delivery, tissue, regenerative and biomedical engineering. In the scope of this study, silica, alginate and alginate-silica hybrid hydrogels were synthesized where gelation was induced by different mechanisms. Formulated gels were characterized by SEM, BET, FTIR and EDS/mapping analysis particularly for the hybrid counterpart. Hydrogels were injected in spiral coil single channel glass-silicon-glass, S-shaped single channel PDMS and 8-channel glass-silicon-glass microsystems. Amino and D-glucono-δ-lactone functionalization for silica and alginate improved the mechanical properties and increased surface area and enzyme activity, respectively. Formulated hybrid gels exhibited a homogeneous structure although aggregation of silica is an important problem leading to loss of porous structure. The results indicated that alginate and hybrid hydrogels exhibited remarkable enhancement for immobilizing enzymes into microsystems and will contribute to the design of new injectable hydrogels particularly for microfluidic applications.

Acknowledgements
The financial supports provided by TUBITAK (113M050) and Ege University Research Fund (15-FBE-012) are highly appreciated. Part of this study was also supported by a grant from TUBITAK 2210-C National Graduate Scholarship Program.

(11:30-11:45 AM) Direct Mechanical Stimulation of MSCs Encapsulated in a Bionanocomposite Magneto-responsive Hydrogel Scaffold via an External Magnetic Field

Adedokun Adedoyin (1) and Adam K. Ekenseair (1) 1. Department of Chemical Engineering, Northeastern University, Boston, MA USA

Injuries sustained to the articular cartilage tissue do not heal naturally due to the tissue’s innate avascular structure. Modern advances in the field of tissue engineering have shown that hydrogels, capable of responding on-demand to changes in their local environment, are promising candidates as injectable scaffolds for osteochondral tissue regeneration applications. This work focuses on the development of an injectable, magneto-responsive pNiPAAm-based hydrogel capable of responding to changes in an external magnetic field to guide the regeneration of damaged cartilage in situ. The magnetic hydrogel scaffold was created by chemically-crosslinking amine-functionalized superparamagnetic iron (III) oxide nanoparticles into the polymer network. Differences in magnetic field stimulation patterns were generated by developing a unique Arduino-controlled electromagnet cell culture system. Results show that these magnetic hydrogels are capable of delivering and maintaining viable stem cell populations. Furthermore, the mechanical stimulation forces created within the hydrogel as a response to changes in the magnetic field did not have any adverse effects on cell viability when compared to our experimental control. Moreover, over a three-week time-period, there was an increase in hydrogel calcification and ALP expression across all experimental conditions. Thus, magneto-responsive hydrogels were shown to be promising candidates as injectable scaffolds for tissue regeneration.

(11:45 AM-12:00 PM) Engineering an elastic hydrogel as a sprayable wound healing patch with antimicrobial properties

Devyesh Rana (1), Ehsan Shirzaei Sani (2), Roberto Portillo Lara (2), Nasim Annabi (2,3,4)

1. Department of Bioengineering, Northeastern University, Boston, MA, 02115-5000, USA
2. Department of Chemical Engineering, Northeastern University, Boston, MA, 02115-5000, USA
3. Biomaterials Innovation Research Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
4. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA

Chronic wounds affect 2% of the U.S. population. Healing of chronic wounds is often impaired by the occurrence of bacterial infections. Therefore, there is a need for wound dressings to promote wound healing and prevent infections. In this study, we engineered novel elastic and sprayable hydrogels with antimicrobial properties, through photopolymerization of various ratios of methacrylated tropoelastin (MeTro) and gelatin methacryloyl (GelMA) for treatment of wound. MeTro/GelMA hydrogels were rendered antimicrobial through the conjugation of the broad spectrum antibacterial peptide (AMP) Tet213. The engineered hydrogels were shown to mimic the mechanical properties of the native tissue and to strongly adhere to native skin. Our results alos demonstrated that 70/30 MeTro/GelMA hydrogels at 15% (w/v) final polymer concentration and 0.01% (w/v) AMP could efficiently inhibited the growth of both Gram positive (Methycilin Resistant Staphylococcus Aureus) and Gram negative (Escherichia Coli) bacteria. MeTro/GelMA hydrogels were shown to promote the proliferation and spread of 3D encapsulated 3T3 fibroblasts in vitro. In addition, they could biodegrade in vivo without eliciting any significant inflammatory response when implanted subqtenously in rats. Our engineered MeTro/GelMA-AMP hydrogel represent a novel sprayable adhesive patch for the clinical management of chronic wounds.

12:00-2:00 PM – LUNCH AND POSTER VIEWING/JUDGING

(2:00-2:15 PM) Cell-Laden Gelatin/Tropoelastin Hydrogel Composites for Peripheral Nerve Repair and Anastomosis

 Jonathan Soucy (1), Ehsan Shirzaei Sani (1), David Diaz Vera (1), Roberto Portillo Lara (1), Felipe Dias (1), Suzanne Mithieux (2), Anthony Weiss (2), Abigail Koppes (1), Ryan Koppes (1), Nasim Annabi (1,3) 1. Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA 2. Bosch Institute, Charles Perkins Centre, & School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia 3. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

A completely or partially severed nerve can cause a patient complete/partial loss of sensation, chronic pain, and even permanent disability. Current guidelines recommend repairing severed nerves with sutures; however, sutures hinder tissue regeneration and often result in scar tissue formation, further preventing functional recovery. To limit the need for sutures, fibrin glue has been proposed as a material to reattach nerve endings, but current formulations are not mechanically robust to significantly reduce the need for sutures. In this report, we engineered photocrosslinkable composite hydrogels from two naturally derived proteins, gelatin and tropoelastin, to be used as a glue for nerve anastomosis. These composites were prepared by conjugating methacrylate groups to gelatin and tropoelastin, then using free-radical chemistry to crosslink the two polymers into an adhesive with tunable physical properties. An in vitro cell study demonstrated that the engineered adhesives supported the growth of both glial and neuronal cells. Furthermore, results from in vivo subcutaneous implantation models demonstrated that the composite is biodegradability and biocompatible. Finally, we confirm that a severed nerve anastomosed by this composite had adhesion strength greater than the commercially available fibrin glue. Taken together, these results demonstrate the potential of gelatin/tropoelastin composites for use in nerve repair.

(2:15-2:30 PM) Prediction of urea cycle disorders via liver-on-a-chip simulation 

Fatemeh Sharifi (1), Bahar Firoozabadi (1) 1. School of mechanical engineering, Sharif university of Technology, Tehran, Iran

Liver has many vital functions without which, human body can survive no more than few days. The role of liver in protein metabolism is probably the most important of its metabolic functions. One major part of this protein metabolism is urea generation. Liver helps to remove Nitrogen groups, Ammonia, from amino acids by generation of urea from amino acids. Ammonia is a very toxic material and if it is not rapidly and efficiently removed from the blood circulation, it will result in central nervous system disease. In this study, first ammonia elimination and urea production was simulated in a microchannel. Then, Twelve rate equations were also solved in order to obtain the concentration of each metabolites participating in urea cycle. Two disorders related to urea cycle i.e. Hyperammonemia and Argininosuccinicaciduria were simulated. Results show a mild decrease and a sharp increase in concentration of the metabolites relating to carbamoyl phosphate synthesis for hyperammonemia type I and II, respectively. Concentration of Argininosuccinate is increased nearly 10 fold in Argininosuccinicaciduria disorder. Predicted results are useful in better understanding, control and managing the effects of metabolite deficiencies, drugs and their side effects on overall metabolic behavior in hepatocytes’ urea cycle.

(2:30-2:45 PM) Effect of pH-Varied Cerium Oxide Nanoparticles on the Growth of Gram-Positive and Negative Bacteria

Ece Alpaslan(1), Benjamin M. Geilich(2), Hilal Yazici(1), Thomas J. Webster(1) 1.Department of Chemical Engineering, Northeastern University, Boston, MA, 02115, USA 2.Department of Bioengineering, Northeastern University, Boston, MA, 02115, USA

The antibacterial activity of dextran-coated nanoceria (DCN) was examined against Pseudomonas aeruginosa and Staphylococcus epidermidis in terms of a dose, time and pH dependent manner. DCN was much more effective at killing P. aeruginosa and S. epidermidis at basic pH (pH=9) compared to an acidic pH environment (pH=6) due to a smaller size and positive surface charge at pH 9. After 6 hours of incubation with nanoceria at pH 9, P. aeruginosa showed drastic morphological changes as a result of cellular stress. This study provides significant evidence for the use of nanoceria for a wide range of anti-infection applications without resorting to the use of antibiotics.

(2:45-3:00 AM) – COFFEE BREAK

(3:00-4:00 PM) – Plenary Invited Speaker, Professor David J. Mooney

 

March 20th, Boston, MA