Surya K. Mallapragada
Professor and
Program Director
Materials Chemistry & Biomolecular Materials
Ames Laboratory
3035 Sweeney Hall
Iowa State University
Ames, IA 50011-2230
Phone (515)294-7407
Fax (515)294-2689
suryakm@iastate.edu
Education
Ph.D., ChE, Purdue University (1996)
B.S., ChE, Indian Institute of Technology, Bombay (1993)
Honors & Awards
Mid-Career Excellence in Research Award, ISU Foundation, 2007
Big 12 Rising Star Award, 2007
Invited participant, National Academy of Engineering, Frontiers in Engineering Conference, 2006
Member, NIH Study Section, Biomaterials & Biointerfaces, 2006
Fellow, AIMBE, 2006
Global Indus Technovator Award, 2003
Named by MIT's Technology Review Magazine as one of the World's Top 100 Young Innovators, 2002
3M Non-tenured Faculty Award, 2001
Early Achievement in Research Award, ISU Foundation, 2001
NSF Faculty Early CAREER Award, 2000
Andrews Graduate Fellowship, Purdue University, 1993-95
Teaching/Office Hours Schedule
We would like to thank NSF, USDOE, USDOD and NIH for supporting our research.
Research Interests
Our research program is focused on designing polymers and biomaterials with tailored micro/nanostructures to precisely control function and properties at the molecular and cellular levels. Our two broad focus areas are: 1) smart polymers and 2) neural tissue engineering.
Research
Smart Polymers
This thrust deals with the synthesis and characterization of novel environmentally-sensitive block copolymers that exhibit unique phase behavior and self-assembly in aqueous solutions across multiple length scales and serve as ideal injectable vectors for drug and gene delivery. Another aspect of this thrust is the development of combinatorial approaches for synthesis of biodegradable polyanhydrides and high-throughput methods for testing drug release profiles from polymers.
Polymer Synthesis and Characterization: We have designed and synthesized novel smart bioinspired multi-block copolymers that exhibit pH and temperature sensitivity. These polymers are cationic and undergo thermoreversible gelation at body temperatures. These polymers exhibit very interesting phase behavior and are the only systems that we are aware of, that can self assemble into ordered macroscale solids, exhibiting self-assembly over length scales of over several orders of magnitude from the nanoscale to the macroscale. We have characterized the unusual phase behavior of these systems using cryo-TEM and small angle X-ray and neutron scattering studies to understand the process of self-assembly into solids.
Applications in Drug Delivery and Gene Therapy: Above a critical gelation temperature and polymer concentration, the micelles formed by the multi-block copolymers described above self-assemble to form macroscale thermoreversible physical gels. Since the critical gelation temperatures are close to room temperature, these polymers can be used as injectable delivery devices and have significant advantages over other crosslinked stimuli-sensitive hydrogels that have been investigated. These physical gels eventually dissolve in the body. The copolymers also exhibit significantly reduced cytotoxicities compared to the parent cationic homopolymers. These polymers are ideal candidates for self-regulating systems for drug delivery. We have obtained insights into dissolution and release mechanisms from these and other gels using novel diffusional and spectroscopic techniques coupled with predictive models. These cationic polymers exhibit complexation with DNA and serve as excellent injectable controlled gene delivery vectors.
Templates for Biomineralization: This new multi-investigator project focuses on growing magnetite nanocrystals using our hierarchically self-assembled polymers described above, using aptamers and mineralization proteins. This approach aims to recreate the structure of magnetite nanocrystals embedded in organic tissue seen in many different living species, that confers super- paramagnetic properties. The combination of the “soft” mechanical properties of the polymer with the strong magnetic response of the magnetite offers new materials properties like giant shape memory effects, field induced deformations, or a magnetic field tuned sound spectrum.
Combinatorial Synthesis of Polyanhydrides for Drug Delivery: The overall goal of this project is to design novel biodegradable nanocarriers for protein stabilization and immune modulation. We have synthesized random copolymers of various anhydride monomers, which play a major role in polypeptide stabilization and vaccine delivery. We have developed high-throughput strategies for synthesizing libraries of polyanhydride copolymers simultaneously. These libraries of copolymers with various compositions are being screened rapidly to obtain information about phase behavior as well as release profiles. We have synthesized a library of 100 different polyanhydride copolymers and characterized it using FTIR microscopy. Altogether, this integrated approach will provide novel insights into the mechanisms of adjuvanticity and tailor the chemistry and size of the biodegradable nanoadjuvants to elicit appropriate immune responses.
Neural Tissue Engineering
Our work in this thrust has focused on using a combination of physical, chemical and biological cues at the cellular level to enable directed and accelerated growth of neurons to facilitate regeneration in the peripheral nervous systems. More recently, we have been investigating the use of these approaches in the central nervous system and also in the use of these specific cues in understanding the growth and differentiation mechanisms of adult neural progenitor cells.
Micropatterned Biodegradable Polymers for Peripheral Nerve Regeneration: Directional nerve growth is important for regeneration. We are using micro/nanopatterned biodegradable polymer substrates to simulate in vivo conditions during peripheral nerve regeneration. Our approach involves utilizing a combination of physical, chemical and biological cues on biodegradable polymer substrates to enhance guided peripheral nerve regeneration. When simultaneously combining the physical effects of the microgrooves, the chemical influence of the laminin and biological enhancements from the Schwann cells, the synergistic effects caused the axons to grow along the direction of the grooves at an accelerated rate. The microgrooved substrates with physical, chemical and biological cues were inserted into conduits and implanted at the site of sciatic nerve transections in rats. The results showed that the functional regeneration of the sciatic nerve was significantly enhanced compared to conventional entubulization strategies.
Effect of Micropatterning and Soluble Cues on Neural Stem Cell Differentiation: We are extending the approaches used for peripheral nerve regeneration to the central nervous system, specifically optic nerve regeneration, using a combination of astrocytes and adult neuronal stem cells on micropatterned substrates. Another aspect of the project is to answer a fundamental question in biology as to how the development of the elaborately organized mammalian brain is orchestrated. To develop a better understanding of the movement and differentiation of adult neural stem cells (NSCs) in vivo, we are collaborating with mathematicians and biochemists to develop a mathematical model, and use a cell culture system involving controlled patterns of extracellular matrix proteins on micropatterned substrates to provide quantitative data for the model. Our recent work has showed that physical cues in the form of micropatterned substrates, in synergy with other cues, preferentially cause NSCs to adopt a neuronal fate as opposed to cells grown on smooth substrates. Our approach provides exquisite spatial microcontrol of cell growth on these substrates.
Selected Recent Publications
Combinatorial Materials Science, Eds. Narasimhan, B. and Mallapragada, S. K., John Wiley (2007).
Agarwal, A., Vilensky, R., Talmon, Y., Unfer, R. and Mallapragada, S. K., “Colloidal Stability and Transfection Efficiency of Novel Self-Assembling Polymeric Gene Delivery Vectors in Serum-Supplemented Media,” J. Controlled Rel., Special issue on Nanomedicine, 121, 28-37 (2007). Invited article.
Agarwal, A., Unfer, R. C., and Mallapragada, S .K. “In Vitro Biocompatibility Testing of Novel Pentablock Copolymers for Gene Delivery,” J. Biomed. Mater Res., Part A, 81A, 24-39 (2007).
Determan, M. D., Cox, J. P. and Mallapragada, S. K., “Drug Release from pH-Responsive Thermogelling Pentablock Copolymers,” J. Biomed. Mater. Res., Part A, 81A, 326-333 (2007).
Enlow, D., Rawal, A., Kanapathipillai, M., Schmidt-Rohr, K., Mallapragada, S. K., Lo, C. T., Thiyagarajan, P., and Akinc, A., “Synthesis and Characterization of Self-Assembled Block Copolymer Templated Calcium Phosphate Nanocomposite Gels,” J. Mater. Chem., 17, 1570-78 (2007). Highlighted as a “hot” article.
Prozorov, T., Wang, L., Palo, P., Nilsen-Hamilton-M, Jones, D., Orr, D., Mallapragada, S., Narasimhan, B., and Prozorov, R., “Cobalt Ferrite Nanocrystals: Outperforming Magnetotactic Bacteria,” ACS Nano, 1, 228-233 (2007).
Prozorov, T., Mallapragada, S. K., Narasimhan, B., Nilsen-Hamilton, M., Williams, T. J., Bazylinski, D., Prozorov, R., and Canfield, P. C., “Protein-Mediated Synthesis of Superparamagnetic Magnetite Nanocrystals,” Adv. Func. Mater., 17, 951-57 (2007).
Prozorov, R., Prozorov, T., Mallapragada, S. K., Narasimhan, B., Williams, T. J., Bazylinski, D., “Magnetic Irreversibility and Verwey Transition in Nano-crystalline Bacterial and Synthetic Magnetite,” Phys. Rev. B., 76, 054406 (2007).
Peleshanko, S., Anderson, K. D., Goodman, M., Determan, M. D., Mallapragada, S. K., and Tsukruk, V., “Thermoresponsive Behavior of Multistimuli Pluronic®-based Pentablock Copolymers at the Air-Water Interface,” Langmuir, 23, 25-30 (2007).
Torres, M. P., Determan, A., Anderson, G., Mallapragada, S. K., and Narasimhan, B., “Amphiphilic Polyanhydrides for Protein Stabilization and Release,” Biomaterials, 28, 108-116 (2007).
Jones, E. B., and Mallapragada, S. K., “Directed Growth and Differentiation of Stem Cells Towards Neural Cell Fates Using Soluble and Surface Mediated Cues,” J. Biomat. Sci. Polym. Ed., 18, 999-1015 (2007).
Schwartz, C., Mallapragada, S. K., and Bahadur, S., “Effect of Crosslinking and Pt-Zr Quasicrystal Fillers on the Mechanical Properties and Wear Resistance of UHMWPE for Use in Artificial Joints,” Wear, 263, 1072-1080 (2007).
