- Kyocera Professor of Materials Science & Engineering
- Adjunct Professor in:
- Department of Radiology
- Department of Neurological Surgery
- Department of Orthopaedics & Sports Medicine
|Office:||302L Roberts Hall|
|Web:||Zhang Web Site|
Ph.D., 1999, University of California at Berkeley, Materials Science & Engineering
M.S., 1993, University of Victoria, Mechanical Engineering, Victoria, B.C., Canada
B.E., 1983, Jiangxi Institute of Metallurgy, Jiangxi, China
Materials Science is a study of the relationship between material structures, properties, and processing conditions. Biomaterials adds a fourth dimension into the picture—the biological system. Just as introducing the time dimension in Physics has broadened our vision about the physical world, the addition of the biological system pushes the frontier of Materials Science to a new horizon and makes materials research incredibly more interesting and challenging. Fundamentally, Biomaterials is a discipline that studies the interactions between materials and biological systems. A biomaterial is designed and processed in such a way that it either triggers, or promotes, or suppresses a biological response depending on the intended application. The problems in Biomaterials need to be addressed at the cellular level, and often, at molecular or nanoscale dimensions. The correlation between Biomaterials and Nanoscience is established naturally and perhaps, inevitably.
Our research is geared toward developing materials and devices for biological and medical applications, which can be broadly categorized in three directions and conducted in three labs within the group.
The Nanoparticle Lab focuses its research on cancer diagnosis and treatment through imaging enhancement and targeted and controlled therapeutic payload delivery. This is accomplished by use of nanoconjugates or multifunctional nanovectors. A nanoconjugate is a chemically modified nanoparticle serving as a “vehicle” that carries biomolecules to target cells. The term “nanovector” here refers to a nano entity that plays a function role in the perspective of therapeutics.
A typical nanovector consists of a nanoparticle core coated with a targeting agent specific to the target cells and a biomolecule with designated functionality. The nanovector must be detectable by at least one characterization technique to validate its location in vivo and to evaluate its therapeutic effects in a time course. The nanovector specifically targets cancer cells and thus imposes minimal side effects to healthy tissue. For therapeutic payload delivery, a mechanism must be established to release the drug from the nanovector after entry to the target cell to induce cellular apoptosis or inhibit cell migration or proliferation. We develop new techniques to synthesize nanoparticles, modify nanoparticles with different chemistries, and functionalize nanoparticles with various targeting agents and therapeutic drugs.
During the past few years, a number of nanoconjugates and nanovectors have been developed in our lab. A recent example is a multifunctional nanovector designed to target and treat glioma, the most common form of primary brain cancer, as well as other cancers of neuroectodermal origin. This nanovector comprises a superparamagnetic iron oxide nanoparticle core coated with a biodegradable polymer PEG, a fluorescence dye Cy5.5 and a targeting agent chlorotoxin. Cy5.5 emits light at near-infrared wavelengths, which unlike visible light, can penetrate several centimeters through brain tissue. This multifunctional nanovector is detectable by both MRI and fluorescence microscopy. Because the MRI and optical signals come from the same nanoparticles, the surgeon would be able to use the MRI scan as a roadmap to the fluorescently labeled glioma within the brain.
Tissue Engineering Lab
The Tissue Engineering Lab concentrates on development of biocompatible materials serving as biodegradable scaffolds and/or drug delivery depots. A scaffold, in the context of tissue engineering and regenerative medicine, is designed to functionally restore or repair diseased or lost tissue in the human body. The current clinical practice in the field relies mainly on allograft and autograft, the surgical procedures that face challenges of severe shortage of resources and risk of disease transmission or viral transfection.
A scaffold is usually made for a particular tissue type to stimulate or accelerate the tissue growth. This process is initiated by encouraging cell attachment, proliferation, and differentiation. The cells populated in the scaffold then “secrete” the natural extracellular matrix as the scaffold gradually degrades. The scaffold should have a highly porous structure with a proper pore size to accommodate cell ingrowth and a degradation rate that matches that of tissue growth. For bone tissue engineering, the scaffold must also have sufficient mechanical strength and a modulus close to that of target tissue.
In general, chemistry, biology, and physical properties need to be considered simultaneously in design to achieve desired outcome. This requirement has led to the development of composite scaffolds wherein each component is responsible for the enhancement of a particular property or functionality. A typical example is a composite scaffold made of a biopolymer and a bioceramic for bone tissue engineering in which the bioceramic strengthens the scaffold structure and forms strong bonding with bone tissue while the biopolymer regulates cell adhesion and the scaffold degradation rate and encapsulates drugs for controlled release.
Scaffolds made of natural polymers are extensively studied in our lab because of their unique tissue compatibility, non-toxic biodegradation products, low immunogenicity, and unlimited resources. A number of scaffolds have been developed for different tissue types in our research group during the past few years. One example is the chitosan-alginate composite porous scaffold made entirely from natural polymers. Chitosan-alginate scaffolding material exhibits significantly-improved biological and mechanical properties as compared to its chitosan counterpart.
Unlike chitosan which generally does not dissolve in solutions of pH > 6, the chitosan-alginate can dissolve in aqueous solutions within a wide range of pH, including physiological pH, which allows for the incorporation of growth factors or other therapeutic proteins with minimal risk of denaturation. In vivo results showed that this material degrades in three months, induces low inflammatory response and scar tissue, and promotes angiogenesis.
Nanofibrous matrices are introduced as scaffolds that may have a better structural resemblance to target tissues than their bulk counterparts, largely because of our ability to manipulate the structure, composition, and chemistry of the matrices at the nanoscale. The concept of biomimetics was introduced many years ago, but only when the materials can be manipulated at the nanoscale, it sheds light on tissue engineering. This is because major components in tissues are nanofeatured structures and cells appear to attach and proliferate better on nanofeatured structures than on bulk materials.
The rapid growing interest in recent years in fabrication of nanofibrous structures is inspired in large part by the advances in electrospinning technology which is capable of producing a variety of polymeric fibers with diameters ranging from a few tens of nanometers to a few microns. However, the nanofibrous matrices cannot completely replace the bulk scaffolds, and a combination of both may prove to yield a better structure than produced by either alone. Research in this area is still in its infancy but is rapidly growing. We fabricate natural polymer based nanofibrous matrices by electrospinning, and study their mechanical and biological properties for tissue engineering and regenerative medicine. The recent examples include chitosan- and alginate- based nanofibrous matrices which demonstrated excellent mechanical properties and cellular compatibility with cartilage and bone cells.
Hydrogels are used in tissue engineering to serve as scaffolds or drug delivery depots for repairing minor tissue defects. Use of injectable hydrogels for sustained drug release avoids surgical procedures for implantation, an advantage simply unbeatable by other approaches. For prolonged drug release, the hydrogel must transform from a liquid to a solid gel in situ upon injection, and this can be accomplished by several mechanisms, including changes in chemical composition, pH value, and temperature at the site of injection. An example of hydrogels developed in our lab is a thermoreversible gel made from chitosan grafted with polyethylene glycol. Unlike other materials which are solid at low temperatures and liquid at high temperatures, this thermoreversible gel undergoes a reversed phase transformation: from an injectable liquid at room temperature or below to a solid gel at body temperature. This hydrogel can be prepared at physiological pH, thus preventing protein denaturation during incorporation. Our in vitro study indicates that protein release from the hydrogel can be sustained from a week up to 40 days.
The Biosensor Lab targets the detection and identification of chemical and biological agents and development of drug screening techniques. We develop surface modification techniques to pattern proteins and live cells on microchips to study their responses to external stimuli. These responses are transformed into optical or electronic signals that are addressed and processed by computers via data acquisition and control interfaces. Cell-based sensors are hybrid systems (biology + device) that utilize cells' remarkable abilities to detect, transduce, and amplify very small changes of chemistry, light, temperature, and other parameters. These sensors will have many applications, including bio-warfare toxin detection, drug evaluation, pollutant identification, and recognition of viruses, bacteria, and cell types in health/food industries.
The major technique used in our lab to pattern live cells is so called “receptor mediated cell adhesion”. In this technique, the adhesive proteins or peptides are selectively immobilized on the electrodes on which cells are subsequently patterned, while the substrate background is rendered chemically inert to resist protein adsorption and cell adhesion. The challenges in cell patterning include cell selectivity (which measures how well the cells are patterned on the designated areas) and long-term viability. Of particular interest is the single cell patterning where each electrode hosts only one cell. Microarrays of single cells allow for fundamental studies of cell biology without the interference of cell-cell contacting signals, require minimal sample volumes, and provide rapid statistical analyses.
We develop new techniques to pattern single cells that can maintain high cell coverage and selectivity, and long-term cellular viability. We have implemented comprehensive optical and electric sensing schemes including hardware development and computational data acquisition and analysis for fast, accurate, and efficient drug screening and toxicity detection. We have integrated our cell patterning techniques with an impedance sensing mechanism in situ to non-invasively study the interactions of single- or multiple- cell sensor arrays with multiple drugs and to evaluate drug efficacy by direct measurement of cellular apoptosis.
Current Research Group
- Research Associates: Narayan Bhattarai
- Graduate Students: Zhensheng ‘Carl’ Li, Dennis Edmondson, Conroy Sun, Jonathan Gunn, Omid Veiseh, Fareid Asphahani, Ashleigh Cooper, Chen Fang
Selected Recent Publications
- N. Kohler, C. Sun, A. Fichtenholtz, J. Gunn, C. Fang, and M. Zhang "Methotrexate Immobilized Poly(ethylene glycol) Magnetic Nanoparticles for MR Imaging and Drug Delivery", Small, accepted.
- C. Sun, R. Sze, and M. Zhang "Folate acid-PEG conjugated superparamagnetic nanoparticles for targeted cellular uptake and detection by MRI", Journal of Biomedical Materials Research, accepted.
- N. Bhattarai, Z. Li, D. Edmondson, and M. Zhang "Alginate-Based Nanofibrous Scaffolds: Structural, Mechanical and Biological Properties", Advanced Materials, accepted.
- M. Veiseh, and M. Zhang "Effect of silicon oxidation on long-term cell selectivity of cell-patterned Au/SiO2 platforms", Journal of the American Chemical Society 128 (4), 1197-1203 (2006).
- N. Bhattara, H. R. Ramay, S. H. Chou, and M. Zhang "Chitosan and lactic acid grafted chitosan nanoparticles as carriers for prolonged drug delivery", International Journal of Nanomedicine, accepted.
- N. Kohler, C. Sun, J. Wang, and M. Zhang "Methotrexate-modified superparamagnetic nanoparticles and their intracellular uptake into human cancer cells”, Langmuir 21 (19), 8858-8864 (2005).
- N. Bhattarai, D. Edmondson, O. Veiseh, F. A. Matsen, and M. Zhang "Electrospun chitosan-based nanofibers and their cellular compatibility”, Biomaterials 26 (31), 6176-6184 (2005).
- Z. Li, and M. Zhang “Chitosan-alginate as scaffolding material for cartilage tissue engineering”, Journal of Biomedical Materials Research 75A (2), 485-493 (2005).
- O. Veiseh, C. Sun, J. Gunn, N. Kohler, P. Gabikian, D.Lee, N. Bhattarai, R.Ellenbogen, R. Sze, A. Hallahan, J. Olson, and M. Zhang "An optical and MRI multifunctional nanoprobe for targeting gliomas”, Nano Letters 5 (6), 1003-1008 (2005).
- H. R. Ramay, Z. Li, E. Shum, and M. Zhang “Chitosan-alginate porous scaffolds reinforced by hydroxyapatite nano- and micro-particles—structural, mechanical, and biological properties”, Journal of Biomedical Nanotechnology 1 (2), 151-160 (2005).
- N. Bhattarai, H. R. Ramay, J. Gunn, F. A. Matsen, and M. Zhang “PEG-grafted chitosan as an injectable thermosensitive hydrogel for sustained protein release”, Journal of Controlled Release 103, 609-624 (2005).
- N. Bhattarai, F. A. Matsen, and M. Zhang “PEG-grafted chitosan as an injectable thermoreversible hydrogel”, Macromolecular Bioscience 5, 107-111 (2005).
- Z. Li, H. Ramay, K. Hauch, D. Xiao, and M. Zhang “Chitosan-alginate hybrid scaffolds for bone tissue engineering”, Biomaterials 26 (18), 3919-3928 (2005).
- S. Lan, M. Veiseh, and M. Zhang "Surface modification of silicon and gold-patterned silicon surfaces for improved biocompatibility and cell patterning selectivity", Biosensors & Bioelectronics 20 (9), 1697-1708 (2005).
UW Department of Materials Science & Engineering
phone: (206) 543-2600
fax: (206) 543-3100