University of Minnesota
Department of Biomedical Engineering
http://www1.umn.edu/bme
612-624-4507

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Chun Wang

Chun Wang

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Biologically Guided Engineering of Polymeric Biomaterials

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.

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

Courses Taught

BMEn 3311/3315 (Spring) - Biomaterials/Biomaterials Lab

BMEn 8001 (Fall) - Polymeric Biomaterials

Selected Publications

W. Lin, S. Hanson, W. Han, X. Zhang, N. Yao, H. Li, L. Zhang, C. Wang.
Well-defined star polymers for co-delivery of plasmid DNA and imiquimod to dendritic cells
Acta Biomaterialia 48, 378–389 (2017)

M. Zhang, Y. Hong, W. Chen, C. Wang.
Polymers for DNA Vaccine Delivery
ACS Biomaterials Science & Engineering DOI: 10.1021/acsbiomaterials.6b00418 (2016)

W. Wang, R. Siegel, C. Wang
Nanocomposite polymers with “slimy” surfaces that refresh following abrasion
ACS Biomaterials Science & Engineering 2(2), 180–187 (2016)

X. Zhong, D. Panus, W. Ji, C. Wang
Modulating polyplex-mediated gene transfection by small-molecule regulators of autophagy
Molecular Pharmaceutics 12, 932–940 (2015)

D. Cross, X. Jiang, W. Ji, W. Han, C. Wang
Injectable Hybrid Hydrogels of Hyaluronic Acid Crosslinked by Well-defined Synthetic Polycations: Preparation and Characterization in vitro and in vivo
Macromolecular Bioscience 15(5), 668-681 (2015)

R. N. Palumbo, W. Han, X. Zhong, D. Panus, W. Ji, C. Wang
Tissue and cellular distribution of naked and polymer-condensed plasmid DNA after intradermal administration in mice
Journal of Controlled Release 159, 232-239 (2012)

R. N. Palumbo, X. Zhong, C. Wang
Polymer-mediated DNA vaccine delivery via bystander cells requires a proper balance between transfection efficiency and cytotoxicity
Journal of Controlled Release 157, 86-93 (2012)

W. Ji, D. Panus, R. N. Palumbo, R. Tang, C. Wang
Poly(2-aminoethyl methacrylate) with well-defined chain-length for DNA vaccine delivery to dendritic cells
Biomacromolecules 12, 4373-4385 (2011)

D. P. Cross, C. Wang
Stromal derived factor 1 alpha-loaded PLGA microspheres for stem cell recruitment
Pharmaceutical Research 28, 2477-2489 (2011)

R. Tang, W. Ji, C. Wang
pH-Responsive micelles based on amphiphilic block copolymers bearing ortho ester pendants as potential drug carriers
Macromolecular Chemistry & Physics 212, 1185-1192 (2011)

R. N. Palumbo, L. Nagarajan, C. Wang
Recombinant monomeric CD40 ligand for delivering polymer particles to dendritic cells
Biotechnology Progress 27, 830-837 (2011)

S. Choh, D. Cross, C. Wang
Facile synthesis and characterization of disulfide-crosslinked hyaluronic acid hydrogels for protein delivery and cell encapsulation
Biomacromolecules 12, 1126-1136 (2011)

R. Tang, W. Ji, D. Panus, R. N. Palumbo, C. Wang
Block copolymer micelles with acid-labile ortho ester side-chains: synthesis, characterization, and enhanced drug delivery to human glioma cells
Journal of Controlled Release 151, 18-27 (2011)

R. Tang, R. N, Palumbo, L. Nagarajan, E. Krogstad, C. Wang
Well-defined block copolymers for gene delivery to dendritic cells: probing the effect of polycation chain-length
Journal of Controlled Release 142, 229-237 (2010)

R. Tang, W. Ji, C. Wang
Amphiphilic block copolymers bearing ortho ester side-chains: pH-dependent hydrolysis and self-assembly in water
Macromolecular Bioscience 10, 192-201 (2010)

R. Tang, R. N. Palumbo, W. Ji, C. Wang
Poly(ortho ester amides): acid-labile temperature-responsive copolymers for potential biomedical applications
Biomacromolecules 10, 722-727 (2009)

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)

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)

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

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