Karen M Haberstroh

Brown University, Providence, RI, United States

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Publications (55)136.52 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The interaction between cells or tissues and natural or synthetic materials which mimic the natural biological environment has been a matter of great interest in tissue engineering. In particular, surface properties of biomaterials (regardless of whether they are natural or synthetic) have been optimized using nanotechnology to improve interactions with cells for regenerative medicine applications. Specifically, in vivo and in vitro studies have demonstrated greater bladder tissue growth on polymeric surfaces with nanoscale to submicron surface features. Improved bladder cell responses on nanostructured polymers have been correlated to unique nanomaterial surface features leading to greater surface energy which influences initial protein interactions. Moreover, coupled with the observed greater in vitro and in vivo bladder cell adhesion as well as proliferation on nanostructured compared to conventional synthetic polymers, decreased calcium stone formation has also been measured. In this article, the importance of nanostructured biomaterial surface features for bladder tissue replacements are reviewed with thoughts on future directions for this emerging field. Copyright (c) 2010 John Wiley & Sons, Inc.For further resources related to this article, please visit the WIREs website.
    Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology 08/2010; · 5.68 Impact Factor
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    ABSTRACT: Obstructive uropathy can cause irreversible renal damage. It has been hypothesized that elevated hydrostatic pressure within renal tubules and/or renal ischemia contributes to cellular injury following obstruction. However, these assaults are essentially impossible to isolate in vivo. Therefore, we developed a novel pressure system to evaluate the isolated and coordinated effects of elevated hydrostatic pressure and ischemic insults on renal cells in vitro. Cells were subjected to: (1) elevated hydrostatic pressure (80 cm H(2)O); (2) ischemic insults (hypoxia (0% O(2)), hypercapnia (20% CO(2)), and 0 mM glucose media); and (3) elevated pressure + ischemic insults. Cellular responses including cell density, lactate dehydrogenase (LDH) release, and intracellular LDH (LDH(i)), were recorded after 24 h of insult and following recovery. Data were analyzed to assess the primary effects of ischemic insults and elevated pressure. Unlike pressure, ischemic insults exerted a primary effect on nearly all response measurements. We also evaluated the data for insult interactions and identified significant interactions between ischemic insults and pressure. Altogether, findings indicate that pressure may sub-lethally effect cells and alter cellular metabolism (LDH(i)) and membrane properties. Results suggest that renal ischemia may be the primary, but not the sole, cause of cellular injury induced by obstructive uropathy.
    Annals of Biomedical Engineering 05/2009; 37(7):1415-24. · 3.23 Impact Factor
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    ABSTRACT: Synthetic polymers have been proposed for replacing resected cancerous bladder tissue. However, conventional (or nanosmooth) polymers used in such applications (such as poly(ether) urethane (PU) and poly-lactic-co-glycolic acid (PLGA)) often fail clinically due to poor bladder tissue regeneration, low cytocompatibility properties, and excessive calcium stone formation. For the successful reconstruction of bladder tissue, polymer surfaces should be modified to combat these common problems. Along these lines, implementing nanoscale surface features that mimic the natural roughness of bladder tissue on polymer surfaces can promote appropriate cell growth, accelerate bladder tissue regeneration and inhibit bladder calcium stone formation. To test this hypothesis, in this study, the cytocompatibility properties of both a non-biodegradable polymer (PU) and a biodegradable polymer (PLGA) were investigated after etching in chemicals (HNO(3) and NaOH, respectively) to create nanoscale surface features. After chemical etching, PU possessed submicron sized pores and numerous nanometer surface features while PLGA possessed few pores and large amounts of nanometer surface roughness. Results from this study strongly supported the assertion that nanometer scale surface roughness produced on PU and PLGA promoted the density of urothelial cells (cells that line the interior of the bladder), with the greatest urothelial cell densities observed on nanorough PLGA. In addition, compared to respective conventional polymers, the results provided evidence that nanorough PU and PLGA inhibited calcium oxalate stone formation; submicron pored nanorough PU inhibited calcium oxalate stone formation the most. Thus, results from the present study suggest the importance of nanometer topographical cues for designing better materials for bladder tissue engineering applications.
    Nanotechnology 03/2009; 20(8):085104. · 3.84 Impact Factor
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    ABSTRACT: The quantified contribution of pure nanometer (features less than 100 nm in both the lateral and vertical scale) and sub-micron (features larger than 100 nm in the lateral scale) surface structures on the adhesion of vascular (endothelial) and bone (osteoblasts) cells were demonstrated in this study. Compared with flat titanium surfaces, sub-micron surface features led to a 27% increase in surface energy and promoted endothelial cell adhesion density by 200%. In addition, nanometer surface features also led to a 10% increase in surface energy and a 50% increase in endothelial cell adhesion density compared to flat titanium surfaces. Using aligned patterns of such features on titanium, it was clearly identified that both endothelial and bone cells selectively adhered onto sub-micron and nanometer surface features by 400% and 50% more than onto flat regions, respectively. Thus, the surface patterns developed in this study clearly confirmed that sub-micron to nanometer titanium surface features enhanced cytocompatibility properties for both endothelial and bone cells. Although sub-micron features on titanium had the highest surface energy and the greatest cell adhesion densities, nanometer surface features in this study were more efficient surface features increasing both surface energy and cell adhesion more with respect to smaller changes in surface area and surface roughness (compared to sub-micron surface features on titanium which had considerably larger changes in surface area and surface roughness).
    Biomaterials 04/2008; 29(8):970-83. · 8.31 Impact Factor
  • Alissa L Russ, Karen M Haberstroh, Ann E Rundell
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    ABSTRACT: Ischemia has elicited a great deal of interest among the scientific community due to its role in life-threatening pathologies such as cancer, stroke, acute renal failure, and myocardial infarction. Oxygen deprivation (hypoxia) associated with ischemia has recently become a subject of intense scrutiny. New investigators may find it challenging to induce hypoxic injury in vitro. Researchers may not always be aware of the experimental barriers that contribute to this phenomenon. Furthermore, ischemia is associated with other major insults, such as excess carbon dioxide (hypercapnia), nutrient deprivation, and accumulation of cellular wastes. Ideally, these conditions should also be incorporated into in vitro models. Therefore, the motivation behind this review is to: i. delineate major in vivo ischemic insults; ii. identify and explain critical in vitro parameters that need to be considered when simulating ischemic pathologies; iii. provide recommendations to improve experiments; and as a result, iv. enhance the validity of in vitro results for understanding clinical ischemic pathologies. Undoubtedly, it is not possible to completely replicate the in vivo environment in an ex vivo model system. In fact, the primary goal of many in vitro studies is to elucidate the role of specific stimuli during in vivo pathological events. This review will present methodologies that may be implemented to improve the applicability of in vitro models for understanding the complex pathological mechanisms of ischemia. Finally, although these topics will be discussed within the context of renal ischemia, many are pertinent for cellular models of other organ systems and pathologies.
    Experimental and Molecular Pathology 11/2007; 83(2):143-59. · 2.13 Impact Factor
  • Saba Choudhary, Karen M Haberstroh, Thomas J Webster
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    ABSTRACT: Vascular tissue possesses numerous nanostructured surface features, but most metallic vascular stents proposed to restore blood flow are smooth at the nanoscale. Thus, the objective of the present study was to determine in vitro vascular cell functions on nanostructured titanium (Ti) compared to conventional commercially pure (c.p.) Ti. Results of this study showed for the first time greater competitive adhesion of endothelial versus vascular smooth muscle cells on nanostructured Ti compared to conventional Ti after 4 hours. Moreover, when cultured separately, increased endothelial and vascular smooth muscle cell density was observed on nanostructured Ti compared to conventional c.p. Ti after 1, 3, and 5 days; endothelial cells formed confluent monolayers before vascular smooth muscle cells on nanostructured Ti. Results also showed greater total amounts of collagen and elastin synthesis by vascular cells when cultured on nanostructured Ti. Since a major mode of failure of conventional vascular stents is the overgrowth of smooth muscle cells compared to endothelial cells, these results suggest that while the functions of both types of vascular cells were promoted on nanostructured c.p. Ti, endothelial cell functions (of particular importance, cell density or confluence) were enhanced over that of vascular smooth muscle cells. Thus, the present in vitro study showed that vascular stents composed of nanometer c.p. Ti particles may invoke advantageous cellular responses for improved stent applications.
    Tissue Engineering 08/2007; 13(7):1421-30. · 4.25 Impact Factor
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    ABSTRACT: Bladder cancers requiring radical cystectomy, along with congenital and acquired disorders which result in obstruction of the bladder, necessitate surgical measures (including augmentation); such diagnoses bring a clinical need for effective bladder replacement implant designs. Many recent approaches for the design of soft tissue replacement materials have relied on the use of synthetic polymeric substances; unfortunately, the optimal soft tissue implant material is yet to be found. This may, in part, be because current polymeric formulations fail to sufficiently biomimic the neighboring bladder tissue. This study took a brand new approach in designing the next generation of tissue-engineered bladder constructs through the use of nanotechnology, or materials with nanometer (less than 100 nm) surface features. Results provided evidence that nano-structured polymeric scaffolds (specifically, PLGA and PU) created using chemical etching techniques are capable of enhancing the human bladder smooth muscle cell adhesion, proliferation, and the production of extracellular matrix (ECM) proteins. Preliminary in vivo results also speak to the usefulness of such nano-structured materials. In combination, these findings suggest that nano-dimensional PLGA and PU scaffolds are promising replacement materials for the human bladder wall.
    Macromolecular Bioscience 06/2007; 7(5):690-700. · 3.74 Impact Factor
  • Derick C Miller, Karen M Haberstroh, Thomas J Webster
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    ABSTRACT: The largest cause of mortality in the Western world is atherosclerotic vascular disease. Many of these diseases require synthetic vascular grafts; however, their patency rate is only 30% in small (<6 mm) diameter vascular grafts after 5 years of implantation. In an effort to increase small diameter vascular graft success, researchers have been designing random nanostructured surface features which enhance vascular cell functions. However, for the present study, highly-controllable, nanostructured features on poly(lactic-co-glycolic acid) (PLGA) surfaces were formulated. To create ordered nanostructured roughness on PLGA surfaces, either 500, 200, or 100 nm polystyrene nanospheres were separately placed onto mica. These were then used as a template for creating an inverse poly(dimethylsiloxane) mold which was utilized to cast PLGA. Compared to all other PLGA films formulated, AFM results demonstrated greater initial fibronectin spreading on PLGA which possessed spherical 200 nm features. Compared to smooth PLGA, PLGA with 500 or 100 nm surface features, results further showed that PLGA with 200 nm spherical features promoted vascular cell (specifically, endothelial, and smooth muscle cell) adhesion. In this manner, the present study demonstrated a specific nanometer surface feature size that promoted fibronectin spreading and subsequent vascular cell adhesion; criteria critical to vascular graft success.
    Journal of Biomedical Materials Research Part A 06/2007; 81(3):678-84. · 2.83 Impact Factor
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    ABSTRACT: To facilitate locomotion and support the body, the skeleton relies on the transmission of forces between muscles and bones through complex junctions called entheses. The varying mechanical and biological properties of the enthesis make healing this avascular tissue difficult; hence the need for an engineered alternative. Cells in situ interact with their environment on the nano-scale which suggests that engineered approaches to enthesis regeneration should include such biologically-inspired nano-scale surface features. The present in vitro study investigated the effects of etching poly-lactic-co-glycolic acid (PLGA) scaffolds to produce nano-topography on the adhesion of fibroblasts and osteoblasts, two integral enthesis cell types. Nano-topography was produced on PLGA by etching the scaffolds in NaOH. Results showed that etching PLGA with NaOH to create nano-scale surface features decreased fibroblast adhesion while it increased osteoblast adhesion; criteria critical for the spatial control of osteoblast and fibroblast adhesion for a successful enthesis tissue engineering material. Thus, the results of this study showed for the first time collective evidence that PLGA can be either treated with NaOH or not on ends of an enthesis tissue engineering construct to spatially increase osteoblast and fibroblast adhesion, respectively.
    International Journal of Nanomedicine 02/2007; 2(3):383-8. · 4.20 Impact Factor
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    ABSTRACT: There are more than 30,000 orthopedic implant revision surgeries necessary each year in part due to poor implant fixation with juxtaposed bone. A further emphasis on the current problems associated with insufficient bone implant performance is the fact that many patients are receiving hip implants earlier in life, remaining active older, and that the human lifespan is continuously increasing. Collectively, it is clear that there is a strong clinical need to improve implant performance through proper, prolonged fixation. For these reasons, the objective of the present in vitro study was to improve the performance of titanium (Ti), one of the most popular orthopedic implant materials. Accordingly, the proliferative response of osteoblasts (bone-forming cells) on novel nanostructured Ti/PLGA (poly-lactic-co-glycolic acid) composites was examined. This study showed that nano-topography can be easily applied to Ti (through anodization) and porous PLGA (through NaOH chemical etching) to enhance osteoblast cell proliferation which may lead to better orthopedic implant performance. This straight forward application of nano-topography on current bone implant materials represents a new direction in the design of enhanced biomaterials for the orthopedic industry.
    International Journal of Nanomedicine 02/2007; 2(3):493-9. · 4.20 Impact Factor
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    ABSTRACT: Arterial homeostasis is dictated by hemodynamics and intercellular communications. Therefore, the present study exposed vascular cells to mechanical forces and conditioned medium to determine the impact of intracellular communication on cell responses. Endothelial cells exposed to flow and flow-conditioned medium demonstrated the most significant up regulation of COX-2 (p
    Chemical Engineering Communications 01/2007; 194(3):309-321. · 1.05 Impact Factor
  • Materials Science Forum - MATER SCI FORUM. 01/2007;
  • Jennifer A. McCann, Thomas J. Webster, Karen M. Haberstroh
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    ABSTRACT: The development of several vascular diseases is linked to both blood flowproperties and cellular behavior in the arterial and venous systems. For instance, atherosclerosis development is dependent on the blood flow profile, shear stress rate, and resulting cellular responses in the arteries. Specifically, in regions of disturbed flow behavior, cells demonstrate both altered morphology and phenotype. Based on this clinical knowledge, in vitro fluid flow studies have been performed on vascular endothelial and smooth muscle cells to understand the process of disease initiation and development. Ultimately, results of such studies will provide knowledge regarding key pathways involved in disease progression. Moreover, this information will be critical when designing effective drug therapies in the clinical setting.
    12/2006: pages 371-394;
  • Karen M Haberstroh
    Nanomedicine 11/2006; 1(3):355-8. · 5.26 Impact Factor
  • Megan A Pattison, Thomas J Webster, Karen M Haberstroh
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    ABSTRACT: Bladder wall resection is often required as a treatment for invasive bladder cancer. When this happens, a suitable replacement material is needed. The present study, therefore, created three-dimensional, porous, nano-structured poly(ether urethane) (PU) matrices for use as bladder tissue-engineering scaffolds. Select cytocompatibility experiments (specifically adhesion and long-term growth studies) were performed on these scaffolds using human bladder smooth muscle cells (BdSMCs). In addition, the amount of total collagen and elastin present in each cell-seeded scaffold was determined since the production of these extracellular matrix (ECM) proteins is essential for the health and survival of cells and for the functionality of the replaced organ. Finally, to better understand how these scaffolds and resident cells would perform in the complex mechanical environment of the bladder wall, scaffolds and cells were subjected to 10 cmH2O pressure using a computer-controlled pressure chamber. Results provided evidence that compared to conventionally used, micro-dimensional PU scaffolds, the novel, nanodimensional scaffolds created in this research increased cell adhesion, growth, and ECM protein production. Additionally, scaffolds and resident cells were not affected by exposure to 10 cmH2O pressure (compared to controls maintained under atmospheric conditions). These results are promising and provide evidence that the nano-dimensional PU scaffolds created in this research are suitable bladder replacement materials that may outperform materials currently used for such purposes.
    Journal of Biomaterials Science Polymer Edition 02/2006; 17(11):1317-32. · 1.70 Impact Factor
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    ABSTRACT: In the body, vascular cells continuously interact with tissues that possess nanostructured surface features due to the presence of proteins (such as collagen and elastin) embedded in the vascular wall. Despite this fact, vascular stents intended to restore blood flow do not have nanoscale surface features but rather are smooth at the nanoscale. As the first step towards creating the next generation of vascular stent materials, the objective of this in vitro study was to investigate vascular cell (specifically, endothelial, and vascular smooth muscle cell) adhesion on nanostructured compared with conventional commercially pure (cp) Ti and CoCrMo. Nanostructured cp Ti and CoCrMo compacts were created by separately utilizing either constituent cp Ti or CoCrMo nanoparticles as opposed to conventional micron-sized particles. Results of this study showed for the first time increased endothelial and vascular smooth muscle cell adhesion on nanostructured compared with conventional cp Ti and CoCrMo after 4 hours' adhesion. Moreover, compared with their respective conventional counterparts, the ratio of endothelial to vascular smooth muscle cells increased on nanostructured cp Ti and CoCrMo. In addition, endothelial and vascular smooth muscle cells had a better spread morphology on the nanostructured metals compared with conventional metals. Overall, vascular cell adhesion was better on CoCrMo than on cp Ti. Results of surface characterization studies demonstrated similar chemistry but significantly greater root-mean-square (rms) surface roughness as measured by atomic force microscopy (AFM) for nanostructured compared with respective conventional metals. For these reasons, results from the present in vitro study provided evidence that vascular stents composed of nanometer compared with micron-sized metal particles (specifically, either cp Ti or CoCrMo) may invoke cellular responses promising for improved vascular stent applications.
    International Journal of Nanomedicine 02/2006; 1(1):41-9. · 4.20 Impact Factor
  • Derick C Miller, Karen M Haberstroh, Thomas J Webster
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    ABSTRACT: Studies have shown that poly(lactic-co-glycolic acid) (PLGA) films with nanometer surface features promote vascular endothelial and smooth muscle cell adhesion. The objective of this in vitro research was to begin to understand the mechanisms behind this observed increase in vascular cell adhesion. Results provided evidence that nanostructured PLGA adsorbed significantly more vitronectin and fibronectin from serum compared to conventional (or those not possessing nanometer surface features) PLGA. When separately preadsorbing both vitronectin and fibronectin, increased vascular smooth muscle and endothelial cell density was observed on nanostructured (compared to conventional) PLGA. Additionally, blocking of cell-binding epitopes of fibronectin and vitronectin significantly decreased vascular cell adhesion on nanostructured (compared to conventional) PLGA. For this reason, results of the present in vitro study demonstrated that cell adhesive proteins adsorbed in different quantities and altered bioactivity on nanostructured compared to conventional PLGA topographies, which (at least in part) may account for the documented increased vascular cell adhesion on nanostructured PLGA. In this manner, this study continues to provide evidence for the promise of nanostructured PLGA in vascular tissue engineering applications.
    Journal of Biomedical Materials Research Part A 07/2005; 73(4):476-84. · 2.83 Impact Factor
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    ABSTRACT: In total, approximately 400 million people worldwide suffer from urinary bladder cancer (Nat Biotechnol 17 (1999) 149). When radical cysectomy is required as treatment, a replacement material is clearly necessitated. For this purpose, three-dimensional poly(lactic-co-glycolic acid) (PLGA) scaffolds were constructed using solvent casting and salt leaching processes. These scaffolds were manipulated to possess nano-dimensional surface features by soaking in sodium hydroxide at select concentrations and for various periods of time. Human bladder smooth muscle cells were then seeded onto these nano-dimensional scaffolds; adhesion and longer-term cell growth experiments were performed for either 4 h, or 1, 3, and 5 days, respectively. Additionally, collagen and elastin production was quantified following each experiment. In all cases, control cells were placed in an incubator and subjected to normal atmospheric pressure, while experimental cells were placed in a pressure chamber and subjected to a sustained pressure of 10 cm H(2)O. Results of this study provided evidence that porous, nano-dimensional polymeric scaffolds enhanced cell adhesion and growth, while also promoting increased elastin and collagen production. Moreover, in general, exposure to pressure did not alter cellular adhesion, growth, or extracellular matrix protein production, which suggests that the scaffolds and their resident cells will fair well in the complex mechanical environment of the bladder wall. In combination, these results provide evidence that the nano-dimensional PLGA scaffolds created in this research are promising as the next generation of bladder wall replacement materials.
    Biomaterials 06/2005; 26(15):2491-500. · 8.31 Impact Factor
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    ABSTRACT: Cardiovascular diseases result in altered endothelial cell functions because of changes in blood flow properties. To understand the relationship between cell environment and behavior, endothelial cell expression of key genes (COX-2, ecNOS, and PDGF-B) was analyzed following exposure to defined mechanical and chemical conditions. Cells were exposed to control medium, control medium and physiological flow, control medium and physiological pressures, control medium and pathological pressures, flow-conditioned medium, flow-conditioned medium and physiological flow, or flow-conditioned medium and physiological pressures. Endothelial cells were sensitive to both their chemical and mechanical environments; for example, while flow, pressure, and flow-conditioned medium each individually affected gene expression, this expression was most dramatically altered when cells were simultaneously exposed to mechanical and chemical stimuli. Interestingly, gene expression following pressure exposure was always less than that following flow. Next, this study began to investigate endothelial cell behavior under pathological flows using a stenotic glass tube with dimensions similar to the carotid artery. Particle image velocimetry (PIV) measurements were utilized to characterize flow within such tubes; in the future, these flow patterns will be correlated with endothelial cell gene expression. Ultimately, these flow-cell relationships may aid in predicting sites of disease expansion downstream of a stenosis.
    Bioengineering Conference, 2005. Proceedings of the IEEE 31st Annual Northeast; 05/2005
  • K.M. Haberstroh, T.J. Webster
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    ABSTRACT: It has been predicted that the highest demand for engineers through the year 2008 will be in the biomedical sector. To meet these needs, the objective of the present study was to increase undergraduate exposure and interest in BME through a research experiences for undergraduates (REU, sponsored by the National Science Foundation) site at Purdue University (https://engineering.purdue.edu/BME/REU/). In achieving these goals, 11 undergraduate student participants conducted BME-related research on the Purdue campus during the summer of 2004. Of these students, 9 were females or underrepresented minorities and 7 had not had hands-on BME experiences prior to the REU program. Each REU student visited 3 BME industries, observed the operating room/clinic, and partook in a bioethics series. In addition, research progress was conveyed through weekly lab meetings and presentation of both a research poster and a formal, 30-minute long, research seminar. To date, cutting-edge research conducted over this and previous summers (2001-2004 in total) has resulted in over 20 manuscripts and over 35 abstracts presented at national BME-related conferences. Finally, survey results provided evidence that REU participants were extremely pleased with the experience and were more likely to enroll in BME graduate programs at the conclusion of the REU program.
    Bioengineering Conference, 2005. Proceedings of the IEEE 31st Annual Northeast; 05/2005

Publication Stats

1k Citations
136.52 Total Impact Points

Institutions

  • 2006–2010
    • Brown University
      • School of Engineering
      Providence, RI, United States
  • 2000–2009
    • Purdue University
      • Weldon School of Biomedical Engineering
      West Lafayette, IN, United States
  • 2002
    • Riley Hospital for Children
      Indianapolis, Indiana, United States
  • 1999–2002
    • Rensselaer Polytechnic Institute
      • Department of Biomedical Engineering
      New York City, NY, United States