NSF Directorate for Engineering | Division of

1. NSF Directorate for Engineering | Division of Chemical, Bioengineering, Environmental, and Transport Systems (CBET) Bioengineering and Engineering Healthcare Cluster Biomedical Engineering Program Director-Semahat Demir, Ph.D.-sdemir@nsf.gov Mission Focus Theme Areas Project Emphasis Interagency Collaborations Awards / Funding Research Examples 1

2. BME Program Mission to provide opportunities to develop novel ideas into discovery-level and transformative projects that integrate engineering and life science principles in solving biomedical problems that serve humanity in the long-term to advance both engineering and life sciences with biomedical engineering projects that are at the interface of engineering and biomedical sciences. 2

3. BME Program Focus Biomedical Engineering Program supports research that applies engineering principles to problems in biology and medicine while advancing the engineering knowledge base.  Integration of engineering expertise with life science principles is an essential requirement for advances in this field.  FAQ: The projects can be with diagnosis or treatment-related goals. The BME program does not support clinical studies. 3

4. Currently, BME Supports Projects in the Following Theme Areas:  Neural engineering  Brain science  Computational neuroscience  Brain-computer interface  Neurotech  Cognitive engineering  Cellular biomechanics Motion, deformation, and forces in biological systems How mechanical forces alter cell growth, differentiation, movement, signal transduction, transport, cell adhesion, cell cytoskeleton dynamics, cell-cell and cell-ECM interactions Genetically engineered stem cell differentiation with long-term impact in tissue repair and regenerative medicine 4

5. High impact transforming technologies New methods, models and tools of understanding and controlling living systems Fundamental improvements in deriving information from cells, tissues, organs, and organ systems New approaches to the design of structures and materials for eventual medical use New methods of reducing health care costs through new technologies Initial evaluation of discovery-level research in a clinical setting but not supporting clinical trials Multi-disciplinary nature, integrating engineering and the life sciences Balanced theory, mathematical modeling, and experiment NOTE: Projects submitted to the BME Program must advance both engineeringandmedical life sciences. BME Unsolicited Projects Should Emphasize: 5

6. Interagency Programs in which BME Currently Participates Collaborative Research in Computational Neuroscience (NSF/NIH) Transforming Biomedicine at the Interface of the Life and Physical Sciences (R01) Program Announcement (PA) Number: PAR-10-141 (NIH/NSF) New Biomedical Frontiers at the Interface of the Life and Physical Sciences (R01) Program Announcement (PA) Number: PAR-10-142 (NIH/NSF) 6

7. Budget FY 2010 - Approximately$10.8 Million Description Total Proposals Received Unsolicited Awards CAREER (70 Proposals) Workshop/Conferences/ and Symposiums Supplements Continuing Grant Increments Panels # of Awards 410 12 10 18 23 20 - - - Total Dollars - - - $3,944,034 $4,499,788 $254,256 $298,353 $1,669,652 $166,385 7

8. ITR: High-Resolution Cortical Imaging of Brain Electrical Activity Bin He - University of Minnesota Functional Neuroimaging of Information Flows within the Brain: Mechanisms of cognitive processes and brain functions 8

9. Neuromuscular Biomechanics CAREER PI: Francisco Valero-Cuevas - Cornell University Analysis of dexterous manipulation; characterization of muscle and brain activity; and computational modeling of dexterity 9

10. Multi-scale modeling of the mouse heart: from genotype to phenotype Andrew D. McCulloch - University of California San Diego A computational model (right) of signaling mechanisms in cardiac muscle cells reproduced experimental measurements of protein kinase A activity gradients (left) in living myocytes and elucidated the role of cAMP diffusion in compartmentation of myocyte signal transduction. BES-0506252 10

11. Colloidal micelles as multifunctional vaccines CAREER PI: Darrell J. Irvine - Massachusetts Institute of Technology Chemoattracting microspheres: Chemoattractants released from hydrogel ‘carrier’ microspheres draw immune cells (dendritic cells) to nanoparticles for delivery of multiple drug signals Nanoparticles containing drug are sequestered inside carrier microsphere until phagocytosed by attracted dendritic cells CBET 0348259 11

12. Aging, Tooth Fracture and the Success of Restorative Dentistry Dwayne D. Arola - University of Maryland Baltimore County Young dentin (age≤30) Old dentin (age≥55) Thespecific aimswere to: 1) Identify the influence of aging on the mechanics of crack growth in dentin, and2) Quantify energy dissipation in dentin using a hybrid approach.The results showed that changes in the microstructure of dentin with age cause a significant reduction in the resistance to both crack initiation and steady-state growth (i.e. toughness). This work is addressing the need for age-specific restorative practices in dentistry.CBET-BES-023823 12

13. NSF/FDA SIR: Fiber-Optic Common-Path Endoscopic Optical Coherence Tomography for Non-Invasive Optical Biopsy Jin U. Kang - Johns Hopkins University Aim: The aim of this work is to investigate a novel method of achieving ultrahigh-resolution, high speed, in-vivo cancer imaging based on common-path endoscopic optical coherence tomography (CP-OCT) Result: The Kang Research Team has fully investigated, experimentally and theoretically, the signal-to-noise issues with both time domain CP-OCT and Fourier-domain CP-OCT. Based on that the Team has optimized the CP-OCT and obtained in-vivo images of rat brain tumors, retina and other tissues. Rat Brain Tumor Frog Retina CBET-0716515 13

14. ITR: High-Resolution Cortical Imaging of Brain Electrical Activity Bin He - University of Minnesota Aim: Develop and evaluate functional neuroimaging techniques integrating functional MRI and EEG source imaging. Results: fMRI and EEG during visual stimulation were acquired simultaneously and integrated together. (a) outside of MRI scanner; (b) inside MRI scanner without fMRI; (c) simultaneous fMRI-EEG recordings. Multimodal neuroimaging shows enhanced spatial resolution compared to source imaging using EEG alone. Image from Im et al., J. Neurosci. Meth, 157(1): 118-123,2006. NSF BES-0411898 14

15. ADVANCE Fellows Award: The Development of a Tissue-Engineered Vascular Graft from Multipotent Adult Progenitor Cells Laura Suggs - University of Minnesota / University of Texas A Expression of angiogenic genes in hMSCs cultures in PEGylated fibrin at days 3, 7 and 14. Results normalized to actin levels and again to expression of hMSCs in fibrin only. B Immunohistochemical staining against CD31(A) and vwf (B) of hMSCs embedded in BTC-PEG fibrin. Nuclear counterstain with DAPI.(20x) Goal: To fabricate a tissue-engineered vascular graft that can be fabricated from a treatedprotein matrix and seeded with bone marrow-derived cells. The differentiated phenotype ofthe cells comprising the graft can be controlled by the matrixResult: A novel matrix was developed based on PEGylated fibrin. The Suggs Team determined that this matrix has the unique ability to promote the transdifferentiation of MSCs towards an endothelial cell phenotype 15

16. Biomimetic Engineering of Responsive Biomaterials Chun Wang - University of Minnesota Ca2+ Aims:1. Investigate the nature and consequence of spasmin conformational change in response to calcium.2. Formulate design criteria for calcium-responsive contractile materials mimicking spasmoneme and test the validity of the design through constructing synthetic polymer hydrogels. Spasmoneme contractile fiber [from Science 2000, 288, 95] Calcium-responsive spasmin hydrogel A model structure of spasmin BES 0547613 16

17. CAREER: Hydrogels for Matrix-Tethered Gene Delivery Tatiana Segura University of California Los Angeles The Segura Research Team is interested in the design and synthesis of hydrogel materials that can deliver DNA to infiltrating cells. The aim of these results was to synthesize an enzymatically degradable hydrogel scaffold that contained DNA nanoparticles that could transfect cells. The Research Team found that cells seeded in this scaffold were able to infiltrate the scaffold, internalize DNA nanoparticles and express the transgene for the 21-days of incubation. 17 CBET-0747539

18. CAREER:Biomechanics of Polymerization Motors and Cell Motility Daniel A Fletcher - University of California-Berkeley The cytoskeleton of cells changes dynamically in response to mechanical forces. In order to study reorganization of the actin cytoskeleton in the direction of an applied force, the Research Team developed a “side view” Atomic Force Microscope. CBET-0348758 18

19. NIRT: Active Nanostructure Enabled On-Chip Spectroscopy System for Cancer Detection Ultimate goal: On-chip spectroscopy system for cancer detection(1)Tunable nanostructure for focusing and frequency selection:Fabricated tunable photonic crystal structure for focusing and spectroscopy (Fig. 1). Also fabricated mechanical actuators (Fig. 2) for mechanical tuning. Currently working on optimizing mechanical flexibility for stable operation.(2)New nanostructure design based on nanoclusters:Demonstrated high-quality periodic array of nanoclusters by template-directed self-assembly (Fig. 3). The new design provides strong magnetic response at optical frequencies.(3)Nanoprobes for biomarker detection:Demonstrated synthesis of nanoprobes and DNA conjugation, Demonstrated detection of point mutation both in solution and in cells, Achieved enhanced sensitivity by scattering measurements. Won Park - University of Colorado 19

20. Multi-Scale Modeling of the Heart: From Genotype to Phenotype Andrew D. McCulloch - University of California San Diego New multi-scale models of cardiac electromechanical interactions, that integrate from molecular to organ system scales, have provided new mechanistic insights into the molecular mechanisms of inherited arrhythmias (in this case LQT3).BES-0506252 20