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 Research Focus of the BME Program The Biomedical Engineering (BME) program supports fundamental, transformative, and discovery research applied to biological systems. 1

2. The mission of BME Program 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. The BME unsolicited projects must o • Be fundamental, transformative, and discovery research • Develop novel ideas integrating engineering and life science principles in solving biomedical problems that serve humanity in the long-term • Focus on high impact transforming methods and technologies and include • methods, models and tools of understanding and controlling of 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; • information technology relevant to biotechnology including bioinformatics; • and new novel methods of reducing health care costs through new technologies • Emphasize the advancement of fundamental engineering knowledge, possibly leading to the development of new methods and technologies • Emphasize novel application of existing technologies to advance fundamental knowledge of both engineering and life science • Highlight multi-disciplinary nature, integrating engineering and the life sciences • Balance theory, mathematical modeling, and experiment 3

4. Answers to FAQs • The Biomedical Engineering (BME) program supports fundamental, transformative, and discovery research applied to biological systems. • Integration of engineering expertise with life science principles is an essential requirement for advances in this field. • Projects submitted to the BME Program must advance both engineering and life sciences and be at the interface of engineering and life sciences. • The projects can be with diagnosis or treatment-related goals in the long-term. The BME program does not support clinical studies. 4

5. The BME program supports projects in the following BME themes: • Neural engineering (brain science, computational neuroscience, neurotech, cognitive engineering) • Cardio/pulmonary systems engineering • Gene and drug delivery systems • Cellular and tissue engineering (cellular biomechanics, genetically engineered stem cell differentiation with long-term impact in tissue repair and regenerative medicine) • Biomaterials and biomimetics • Computational modeling, multiscale modeling, biocomplexity [applied to only the theme(s) above] 5

6. 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 6

7. 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 7

8. 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 8

9. CAREER: Educational Program in Neuromuscular Biomechanics and Uncovering the Neuromuscular Biomechanics of Dexterous Manipulation Aims: To quantify the sensorimotor capabilities of the brain-hand system for dexterous manipulationResults: 1) Healthy people all have a veryconsistent limit of dexterity 2) Specific diseases have “signatures,” which enable quantification of impairment and recovery 3) The Research Team can systematically test the neuromechanical control of the fingers and networks of brain activity to study the neuroanatomical foundations ofdexterous manipulation 4) We are applying this to study the development of dexterity in children Francisco Valero-Cuevas - University of Southern California CBET-BES-0237258 9

10. ADVANCE Fellows Award: The Development of a Tissue-Engineered Vascular Graft from Multipotent Adult Progenitor Cells Laura Suggs - University of Minnesota / University of TexasGoal: 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 A B 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. Immunohistochemical staining against CD31(A) and vwf (B) of hMSCs embedded in BTC-PEG fibrin. Nuclear counterstain with DAPI.(20x) 10

11. Biomimetic Engineering of Responsive Biomaterials 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. Chun Wang - University of Minnesota Spasmoneme contractile fiber [from Science 2000, 288, 95] Calcium-responsive spasmin hydrogel A model structure of spasmin BES 0547613 11

12. 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. 12 CBET-0747539

13. 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 13

14. 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 14

15. 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 15