Chun Wang Assistant Professor 612-626-3990 email: wangx504@umn.edu

Biologically guided engineering of polymeric biomaterials

• B.S., Chemistry, Nankai University, China, 1992
• M.S., Bioengineering, University of Utah, 1998
• Ph.D., Bioengineering, University of Utah, 2001
• NIH Postdoctoral Fellow, Chemical Engineering, MIT, 2004

Honors and awards

• Dow Corning Graduate Student Outstanding Research Award, Controlled Release Society, 1998
• Capsugel Award for Innovative Aspects of Controlled Drug Release, Controlled Release Society, 1999
• Individual National Research Service Award (postdoctoral), National Institutes of Health, 2002
• CAREER Award, National Science Foundation, 2006
• Early Career Translational Research Award, Wallace H. Coulter Foundation, 2007
• McKnight Land-Grant Professorship, University of Minnesota, 2007-2009

Teaching

BMEn 5001 (Fall semester): Advanced Biomaterials
BMEn 8xxx (Spring semester): Polymeric Biomaterials

Research summary

No matter what the application may be, biomaterials of the future are likely to be multifunctional, bio-responsive, and well-defined. We are interested in exploring how to engineer polymers so we can build such biomaterials and use them to solve problems in biology and medicine. To accomplish this, we draw inspirations and design principles from biology and merge expertise from many disciplines including polymer chemistry, protein engineering, macromolecular assembly, immunology, physiology, and stem cell biology. We strive to develop polymers and nano-materials that are biologically compatible, target specific cells and tissues in the body, and change their properties in response to physiological signals. Such “smart” biomaterials can be useful vehicles for delivering drugs to treat diseases without toxic side-effects. Or they may serve as building blocks for constructing implantable scaffolds that harness and promote the intrinsic healing and regenerative power of stem cells.

Polymers for gene and drug delivery

Effective and safe drug therapy requires precise delivery of drugs to the right place, at the right time, with the right dose. Targeted drug delivery, or the “magic bullet”, has been intensely investigated over the last several decades, with promising yet limited success. The ideal drug delivery materials should be able to not only target specific tissues and organs, but also release drugs inside cells on demand, while the vehicles themselves can be degraded, absorbed or excreted by the body safely. The challenge of delivery becomes more daunting in the cases of gene therapy and genetic vaccination, when nucleic acid such as DNA or RNA is used as a drug or vaccine.

Viruses are supra-molecular colloidal particles that package genetic information and propagate themselves through infecting cells. Viral particles are structurally highly defined in multiple length-scales. They are also highly dynamic structures that respond “intelligently” to different cellular environment, helping orchestrate the complex processes involved in gene transfer. Since the early days of gene therapy, viral particles have been the inspiration for the design of synthetic, non-viral gene delivery vectors that could be potentially useful in treating many diseases. In our lab, we use a variety of tools, including synthetic polymer chemistry and protein engineering, to synthesize polymers and nano-materials that are biologically compatible and recapitulate certain structural and functional features of viruses. For example, we use “living” polymerization techniques to synthesize block copolymers with defined chain-length to mimic the highly defined nature of viral components. We also synthesize biodegradable polymers based on ortho esters that undergo accelerated hydrolysis triggered by mildly acid pH environment found in the endosome, a subcellular organelle of mammalian cells, to mimic the pH-triggered conformational change found in many viral vectors during gene transfer. Furthermore, specific ligands are engineered and incorporated with the polymers to achieve specific targeting to certain cell types. Our current interest is using these polymers to deliver DNA vaccine to antigen-presenting dendritic cells and modulate their phenotypic maturation that lead to enhanced antigen-specific immune responses for the treatment of a wide range of diseases including cancer. We are particularly interested in understanding the immunological mechanisms of polymer-mediated DNA vaccine delivery in cultured immune cells and in vivo.

Polymers as synthetic stem cell niches for tissue repair and regeneration

Stem cell niche refers to specialized in vivo microenvironments that maintain and regulate self-renewal, survival, proliferation, migration, and differentiation of stem cells. It is the natural habitat of stem cells that integrates spatiotemporal instructive cues, enabling stem cells to respond to the need of maintaining homeostasis of the organism. A typical stem cell niche is a physically constrained 3-dimensional space, within which the stem cell receives two forms of signals: 1) contact-mediated insoluble signals from niche cells and the extracellular matrix, and 2) soluble paracrine and endocrine signals from local niche cells and distant sources. The dynamic nature of niches allows the instructive signals to be altered, when stem cells are needed to mobilize and initiate their intrinsic differentiation program for the repair and regeneration of tissues and organs in response to injury or disease.

Our long-term goal is to develop implantable multifunctional biomaterials that serve as synthetic cell niches, capable of integrating instructive molecular signals for promoting recruitment, retention, survival, proliferation, and differentiation of stem/progenitor cells, ultimately leading to significant improvement of the clinical outcome of cell therapy. As a first step toward this long-term goal, we are developing novel injectable polymer hydrogels with tunable bulk and degradation properties that may serve as three-dimentional material platforms to provide sustained gradients of soluble signals and tethered insoluble signals precisely defined at the nano-scale. We envision that such synthetic niches may be implanted in the injured tissue through minimally invasive ways with or without the inclusion of exogenous stem cells.
We are also exploring polymer-based strategies to create niches in which individual stem cells can be confined, addressed, and manipulated. Creating synthetic stem cell niches requires constructing multifunctional, multi-component polymer systems more sophisticated than any man-made biomaterial scaffold known to date. This challenge will put to test our ability of biomaterial engineering through truly integrating biological principles with novel material design and synthetic methodologies.

Selected publications

D. N. Nguyen, S. S. Raghavan, L. M. Tashimad, E. C. Lin, S. J. Fredette, R. S. Langer, C. Wang
Enhancement of poly(ortho ester) microspheres for DNA vaccine delivery by blending with poly(ethylenimine).
Biomaterials 29, 2783-2793 (2008)

C. Wang, P. T. Pham
Polymers for viral gene delivery.
Expert Opinion on Drug Delivery 5, 385-401 (2008)

H. Zhang, D. Yee, C. Wang
Quantum dots for cancer diagnosis and therapy: biological and clinical perspectives.
Nanomedicine 3, 83-91 (2008)

H. Zhang, D. Sachdev, C. Wang, A. Hubel, M. Gaillard-Kelly, D. Yee
Detection of tye I IGF receptor expression and downregulation by antibody-conjugated quantum dots in breast cancer cells.
Breast Cancer Research & Treatment (DOI 10.1007/s10549-008-0014-5, published on April 17, 2008)

N. Palumbo, C. Wang
Bacterial invasin: structure, function, and implication for oral gene delivery.
Current Drug Delivery 3, 47-53 (2006)

J. Yang, C. Xu, C. Wang, J. Kopecek
Refolding hydrogels self-assembled from HPMA graft copolymers by antiparallel coiled-coil formation.
Biomacromolecules 7, 1187-1195 (2006)

C. Wang, N. Flynn, R. Langer
Controlled structure and properties of thermo-responsive nanoparticle-hydrogel composites.
Advanced Materials 16, 1074-1079 (2004)

C. Wang, Q. Ge, D. Ting, D. Nguyen, H. R. Shen, J. Chen, H. N. Eisen, J. Heller, R. Langer, D. Putnam
Molecularly engineered poly(ortho ester) microspheres for enhanced delivery of DNA vaccines.
Nature Materials 3, 190-196 (2004)

M. M. Stevens, N. Flynn, C. Wang, D. A. Tirrell, R. Langer
Coiled-coil peptide based assembly of gold nanoparticles.
Advanced Materials 16, 915-918 (2004)

C. Wang, N. Flynn, R. Langer
Morphologically well-defined gold nanoparticles embedded in thermo-responsive hydrogel matrices
Materials Research Society Symposium Proceedings 820, “Nanoengineered Assemblies and Advanced Micro/Nanosystems”, R2.2.1-R.2.2.6 (2004)

C. Xu, L. Joss, C. Wang, M. Pechar, J. Kopecek
The influence of fusion sequences on the thermal stabilities of coiled-coil proteins.
Macromolecular Biosciences 2, 395-401 (2002)

C. Wang, J. Kopecek, R. J. Stewart
Hybrid hydrogels crosslinked by genetically engineered coiled-coil block proteins.
Biomacromolecules 2, 912-920 (2001)

A. Tang, C. Wang, R. J. Stewart, J. Kopecek
The coiled-coil motif in the design of protein-based constructs: hybrid hydrogels and epitope displays.
Journal of Controlled Release 72, 57-70 (2001)

J. Kopecek, A. Tang, C. Wang, R. Stewart
De novo design of biomedical polymers: hybrid from synthetic macromolecules and genetically engineered protein domains.
Macromolecular Symposia 174, 31-42 (2001)

A. Tang, C. Wang, R. J. Stewart, J. Kopecek
Self-assembled peptide exposing epitopes recognizable by human lymphoma cells.
Bioconjugate Chemistry 11, 363-371 (2000)

C. Wang, R. J. Stewart, J. Kopecek
Hybrid hydrogels assembled from synthetic polymers and coiled-coil protein domains.
Nature 397, 417-421 (1999)

Q. Zhang, C. Wang
Polyhydroxybutyrate produced from cheap resources. I. Crystallization and melting behavior.
Journal of Applied Polymer Science 54, 515-518 (1996)