Wearable Graphene-Based Sensors and Supercapacitors
We recently invented the inkjet printing and thermal reduction of graphene oxide nanosheets, as a new means of fabricating graphene electrodes for producing flexible and therefore wearable sensors and supercapacitor electrodes. Graphene is an ideal material for these emerging applications because of its unique set of interesting properties: (1) mechanically strong and yet very conformal and flexible like if one can envision a nanoscale silk scarf, (2) electrochemically stable, (3) electrically conductive, and (4) affordable as it can be produced from graphite powder mined from earth. Also, it can be assembled during inkjet printing to generate very high surface area and optimum nanoscale porosity for supercapacitor applications.
Our current effort on supercapacitors is aimed at further improving the performance of graphene electrodes and prototyping truly flexible supercapacitors with “roll-to-roll” compatible materials and packaging for their wearable use with fast charge/discharge rates in seconds while being able to withstand millions of charge/discharge cycles. For sensor applications, we are integrating the temperature sensing capability of our graphene material for wearable health monitoring devices as well as exploring the ability of our material to sense human electrophysiological functions.
This research is conducted in collaboration with FlexTraPower, a Stevens startup company and the U.S. Army Research Laboratory.
Microphysiological 3D Tissue and Tumor Engineering – Overview
We are exploring the feasibility of developing microphysiological relevant human 3D tissue models as a new means for: (1) preclinical drug evaluation to reduce our reliance on animal models that have limited relevance to humans and therefore poorly correlated with clinical outcomes and (2) patient-specific diagnostic screening of therapeutic options, for example, for optimum care of cancer patients. The development of this exciting technology requires significant advances on three major research fronts: (1) ability to work with primary cells which are often difficult to preserve and maintain ex vivo beyond a few passages; (2) reconstructing 3D tissue structures, through the enabling use of biomaterials, that mimic native microenvironments from which primary cells are harvested from; and (3) culture devices that can be easily used in typical biology laboratories to grow 3D tissues and evaluate tissue cell response to drugs in a relatively high-throughput manner. The use of primary cells is important since immortalizing human cells into cell-lines by gene transfection perturbs the cells’ gene expression profiles and cellular physiology as well as physical integrity of their genome. Also, recent research by many investigators has demonstrated the value of using 3D tissue cell culture for reproducing authentic cell phenotypes and functions. Furthermore, perfusion culture is desired to mimic: (1) mechanical forces and mass transfer conditions associated with physiological microenvironments and (2) circulatory cell functions associated with reconstructing physiologically interactive tissues. We are approaching this new technology development through concept demonstration towards several clinically important applications.
Patient-Specific 3D Tumor Model for Multiple Myeloma
Multiple myeloma (MM), an incurable B cell malignancy, is the second most common blood cancer in the U.S. with a typical survival of 5 to 7 years. This disease is characterized by monoclonal proliferation of malignant plasma cells in the bone marrow (BM), the presence of high levels of monoclonal serum antibody, and the development of osteolytic bone lesions. Unfortunately, progress in understanding and treating the disease has been significantly limited by the fact that primary human MM tumor cells have been difficult to maintain and propagate ex vivo. The difficulty is due to the lack of an in vitro technology capable of reproducing the complex bone marrow microenvironments at the interface region between bone and bone marrow tissues.
In collaboration with Dr. Jenny Zilberberg and Dr. David Siegel, MD, at Hackensack University Medical Center, we are exploring a new approach to emulate the bone marrow microenvironments in vitro and therefore to maintain and expand primary human multiple MM cells ex vivo. The system uses a three-dimensional (3D) ossified tissue to mimic the tumor niche and particularly to recapitulate adhesive interactions between MM cells and osteoblasts residing at the tissue interface between bone and bone marrow, i.e., endosteum. Our “ex vivo tumor engineering” approach is anticipated to provide a new avenue that can facilitate: (1) diagnostic testing of personalized therapeutics for MM patients, (2) preclinical evaluation of new drugs without the need for costly animal models, and (3) studying the biology of MM and in particular the mechanisms responsible for drug resistance and relapse associated with this incurable cancer. Beyond multiple myeloma, our ability to conserve the endosteum niche is expected to be useful in studying solid tumors like breast and prostate cancers that metastasize to the bone through the same endosteum niche.
This research is supported by the National Cancer Institute of the National Institutes of Health through Grant 1R21CA174543-01A1 and Onyx Pharmaceuticals.
Microfluidic 3D Culture of Primary Murine Osteocytes
The goal of this research is to develop an in vitro microfluidic culture device that can be used to reproduce the mechanotransduction function of osteocytes, residing in cortical bones of mice. As master regulators of homeostatic bone remodeling, osteocytes embedded are known to sense local compressive strain and initiate strain-dependent new bone formation by osteoblasts with sclerostin as one of major signaling molecules. Despite of this important understanding, there is currently no in vitro model that is capable of reproducing the physiological phenotype and mechanotransduction function of primary osteocytes for routine use in biomedical research and preclinical drug evaluation.
We hypothesize that microbeads can be used to guide the re-establishment of 3D cellular networks of primary osteocytes harvested from mice during microfluidic perfusion culture. The microbeads are being engineered to mimic, upon their close packed assembly with osteocytes in the microfluidic culture chamber, the geometry and mechanical support function of the extracellular matrix of bones. The microfluidic culture device is also used to: (1) apply compressive cycling loading to 3D osteocyte networks reconstructed in the culture chamber and (2) reproduce the strain-sclerostin relationship observed by in vivo studies. Comparison to the in vivo data of the mouse ulna loading study will scientifically validate the use of the proposed in vitro device, as a novel means of studying fundamental biological mechanisms associated with osteocytes as master regulators of bone remodeling. Also, the comparison will provide new significant insight for parallel development to culture primary human osteocytes and extend the microfluidic device’s capability for simulating human bone remodeling that includes osteocyte-regulated bone formation and bone resorption.
This research is conducted in collaboration with Dr. Jenny Zilberberg at Hackensack University Medical Center and Prof. Antonio Valdevit at Stevens, and is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health through Grant 1R21AR065032-01.
The goal of this project is to reconstruct in vitro 3D lacunocanalicular network structure of cortical human bones. In order to mimic the network’s multi-scale 3D geometrical features, a biomimetic approach will be used to hierarchically assemble microbeads and nanoparticles with primary osteocyte cells harvested from human bones. The specific objectives of the project are to: (1) investigate the effects of biphasic calcium phosphate and hydroxyapatite nanoparticles on extracellular matrix production by human primary osteocytes and remodeling of their lacunocanalicular space and (2) reproduce the physiological role of the reconstructed osteocyte network in incorporating neighboring osteoblasts into the cellular network and regulating the spatiotemporal transition of the osteoblasts to osteocytes, as mechanisms by which new bone tissue is formed during homeostatic bone remodeling.
The regulation of osteoblasts by osteocytes for new bone formation is a major target for development of new drugs for treating 10 million osteoporosis patients and cancer patients with bone metastases which result in 350,000 deaths every year in the U.S. For these diseases, our human tissue reconstruction approach will provide a more clinically relevant means of evaluating drugs than animal testing, as the latter is known to poorly predict drug response in humans. This study will, therefore, offer an important new insight in addressing or pharmaceutical industry’s need to lower the number of costly drug failures that occur during clinical trials.
This research is conducted in collaboration with Dr. Jenny Zilberberg at Hackensack University Medical Center, and is supported by the National Science Foundation through Grant DMR-1409779.