Resume

• 2006

  Ph.D.

  Biomedical Engineering

• 2002

  B.S.

  Mechanical Engineering

• 2001

  B.S.

  Chemical Engineering

  Graduate Teacher Certificate

  Purdue University Center for Instructional Excellence

• 1995

  Computer Science

  High School

• 19

  Osteogenesis is a complex process that involves the synergistic contribution of multiple cell types and numerous growth factors (GFs). To develop effective bone tissue engineering strategies employing GFs

  it is essential to delineate the complex and interconnected role of GFs in osteogenesis. The studies investigating the temporal involvement of GFs in osteogenesis are limited to in vitro studies with single cell types or complex in vivo studies. There is a need for platforms that embody the physiological characteristics and the multicellular environment of natural osteogenesis. Marrow tissue houses various cell types that are known to be involved in osteogenesis

  and in vitro cultures of marrow inherently undergo osteogenesis process. Self-inductive ossification of marrow explants in vitro can be employed as a representative multicellular and three-dimensional model of osteogenesis. Therefore

  the aims of this study were to employ the rat bone marrow explant ossification model to determine (1) the temporal production profiles of key GFs involved in osteogenesis

  (2) the relation between GF production and ossification

  and (3) the relations between the GF levels throughout ossification. Temporal production profiles of transforming GF β-1 (TGF-β1)

  bone morphogenetic protein-2 (BMP-2)

  vascular endothelial GF (VEGF)

  and insulin-like GF-1 (IGF-1) and the bone-related proteins alkaline phosphatase and osteocalcin were obtained by enzyme-linked immunosorbent assays conducted at days 2

  and 21. The final amount of ossification (ossified volume [OV]) was measured by microcomputed tomography at day 21. TGF-β1

  BMP-2

  VEGF

  IGF-1

  alkaline phosphatase

  and osteocalcin were produced by the ossifying marrow explants differentially over time. Therefore

  tissue engineering strategies toward bone regeneration should consider the richness of GFs involved in osteogenesis and their dynamically varying participation over time.

  The Sequential Production Profiles of Growth Factors and their Relations to Bone Volume in Ossifying Bone Marrow Explants

  Tian Jian Lu

  Shuqi Wang

  Hikmet Geckil

  Sangjun Moon

  Low-cost

  robust

  and user-friendly diagnostic capabilities at the point-of-care (POC) are critical for treating infectious diseases and preventing their spread in developing countries. Recent advances in micro- and nanoscale technologies have enabled the merger of optical and fluidic technologies (optofluidics) paving the way for cost-effective lensless imaging and diagnosis for POC testing in resource-limited settings. Applications of the emerging lensless imaging technologies include detecting and counting cells of interest

  which allows rapid and affordable diagnostic decisions. This review presents the advances in lensless imaging and diagnostic systems

  and their potential clinical applications in developing countries. The emerging technologies are reviewed from a POC perspective considering cost effectiveness

  portability

  sensitivity

  throughput and ease of use for resource-limited settings.

  Miniaturized lensless imaging systems for cell and microorganism visualization in point-of-care testing

  Baoqiang Li

  Venkatakrishnan Rengarajan

  Chung-an Max Wu

  A new biomaterial (M-gel) is developed by incorporating magnetic nanoparticles into microscopic hydrogels. The material maintains the biocompatibility of the hydrogels

  while contributing additional capabilities for culture and magnetic manipulation. These M-gels can be used as building blocks to create 3D complex multilayer constructs using external magnetic fields.

  Three-Dimensional Magnetic Assembly of Microscale Hydrogels

  Adam Krueger

  Mechanical cues play an important role in bone regeneration and affect production and secretion dynamics of growth factors (GFs) involved in osteogenesis. The in vitro models for investigating the mechanoresponsiveness of the involvement of GFs in osteogenesis are limited to two-dimensional monolayer cell culture studies

  which do not effectively embody the physiological interactions with the neighboring cells of different types and the interactions with a natural extracellular matrix. Natural bone formation is a complex process that necessitates the contribution of multiple cell types

  physical and chemical cues in a three-dimensional (3D) setting. There is a need for in vitro models that represent the physiological diversity and characteristics of bone formation to realistically study the effects of mechanical cues on this process. In vitro cultures of marrow explants inherently ossify and they embody the multicellular and 3D nature of osteogenesis. Therefore

  the aim of this study was to assess the mechanoresponsiveness of the scaffold-free

  multicellular and 3D model of osteogenesis based on inherent marrow ossification and to investigate the effects of mechanical loading on the osteoinductive GF production dynamics of this model. These aims were achieved by: a) culturing rat bone marrow explants for 28 days under basal conditions which facilitate inherent ossification

  b) employing mechanical stimulation (compressive loading) between days 12 and 26; c) quantifying the final ossified volume and the production levels of BMP-2

  VEGF

  IGF-1 and TGF-β1. In conclusion

  this study demonstrates that the scaffold-free

  multicellular and 3D model of bone formation based on inherent ossification of marrow tissue is mechanoresponsive and mechanical loading improves in vitro osteogenesis in this model with sustaining or enhancing osteoinductive GF production levels which otherwise would decline with increasing time.

  Ossifying Bone Marrow Explant Culture as a Three-dimensional Mechanoresponsive In Vitro Model of Osteogenesis

  Umut A.

  Gurkan

  MIT

  Brigham and Women's Hospital

  Purdue University

  Case Western Reserve University

  Hemex Health

  Inc.

  Harvard Medical School

  Cleveland/Akron

  Ohio Area

  Warren E. Rupp Associate Professor

  Case Western Reserve University

  Purdue University

  Postdoctoral Research Fellow in Medicine

  Division of Biomedical Engineering

  Brigham and Women's Hospital

  Postdoctoral Research Fellow in Medicine

  Harvard Medical School

  Postdoctoral Research Fellow

  Harvard-MIT Health Sciences and Technology

  MIT

  Case Western Reserve University

  Cleveland

  OH

  Mechanical and Aerospace Engineering

  Assistant Professor

  Portland

  Oregon Area

  Chief Scientist in Microfabricaton

  Hemex Health

  Inc.

  Cleveland/Akron

  Ohio Area

  Warren E. Rupp Assistant Professor

  Case Western Reserve University

  IEEE-Engineering in Medicine and Biology Society

  Partners in Excellence Award for Outstanding Community Contributions

  Brigham and Women's Hospital

  Harvard Medical School

• Biomaterials

  Microfluidics

  Microscopy

  Tissue Engineering

  Biotechnology

  biomanufacturing

  biofabrication

  Scanning Electron Microscopy

  Image Analysis

  Cell Biology

  Confocal Microscopy

  Cell

  ELISA

  In Vitro

  Characterization

  advanced manufacturing

  Nanotechnology

  Biomedical Engineering

  Fluorescence Microscopy

  Western Blotting

  Comparison of morphology

  orientation

  and migration of tendon derived fibroblasts and bone marrow stromal cells on electrochemically aligned collagen constructs

  Xingguo Cheng

  There are approximately 33 million injuries involving musculoskeletal tissues (including tendons and ligaments) every year in the United States. In certain cases the tendons and ligaments are damaged irreversibly and require replacements that possess the natural functional properties of these tissues. As a biomaterial

  collagen has been a key ingredient in tissue engineering scaffolds. The application range of collagen in tissue engineering would be greatly broadened if the assembly process could be better controlled to facilitate the synthesis of dense

  oriented tissue-like constructs. An electrochemical method has recently been developed in our laboratory to form highly oriented and densely packed collagen bundles with mechanical strength approaching that of tendons. However

  there is limited information whether this electrochemically aligned collagen bundle (ELAC) presents advantages over randomly oriented bundles in terms of cell response. Therefore

  the current study aimed to assess the biocompatibility of the collagen bundles in vitro

  and compare tendon-derived fibroblasts (TDFs) and bone marrow stromal cells (MSCs) in terms of their ability to populate and migrate on the single and braided ELAC bundles. The results indicated that the ELAC was not cytotoxic; both cell types were able to populate and migrate on the ELAC bundles more efficiently than that observed for random collagen bundles. The braided ELAC constructs were efficiently populated by both TDFs and MSCs in vitro. Therefore

  both TDFs and MSCs can be used with the ELAC bundles for tissue engineering purposes.

  Comparison of morphology

  orientation

  and migration of tendon derived fibroblasts and bone marrow stromal cells on electrochemically aligned collagen constructs

  Bone marrow is a viscous tissue that resides in the confines of bones and houses the vitally important pluripotent stem cells. Due to its confinement by bones

  the marrow has a unique mechanical environment which has been shown to be affected from external factors

  such as physiological activity and disuse. The mechanical environment of bone marrow can be defined by determining hydrostatic pressure

  fluid flow induced shear stress

  and viscosity. The hydrostatic pressure values of bone marrow reported in the literature vary in the range of 10.7–120 mmHg for mammals

  which is generally accepted to be around one fourth of the systemic blood pressure. Viscosity values of bone marrow have been reported to be between 37.5 and 400 cP for mammals

  which is dependent on the marrow composition and temperature. Marrow’s mechanical and compositional properties have been implicated to be changing during common bone diseases

  aging or disuse. In vitro experiments have demonstrated that the resident mesenchymal stem and progenitor cells in adult marrow are responsive to hydrostatic pressure

  fluid shear or to local compositional factors such as medium viscosity. Therefore

  the changes in the mechanical and compositional microenvironment of marrow may affect the fate of resident stem cells in vivo as well

  which in turn may alter the homeostasis of bone. The aim of this review is to highlight the marrow tissue within the context of its mechanical environment during normal physiology and underline perturbations during disease.

  The Mechanical Environment of Bone Marrow: A Review

  Teresita M. Bellido

  Keith W. Condon

  In vitro models of osteogenesis are essential for investigating bone biology and the effects of pharmaceutical

  chemical

  and physical cues on bone formation. Osteogenesis takes place in a complex three-dimensional (3D) environment with cells from both mesenchymal and hematopoietic origins. Existing in vitro models of osteogenesis include two-dimensional (2D) single type cell monolayers and 3D cultures. However

  an in vitro scaffold-free multicellular 3D model of osteogenesis is missing. We hypothesized that the self-inductive ossification capacity of bone marrow tissue can be harnessed in vitro and employed as a scaffold-free multicellular 3D model of osteogenesis. Therefore

  rat bone marrow tissue was cultured for 28 days in three settings: 2D monolayer

  3D homogenized pellet

  and 3D organotypic explant. The ossification potential of marrow in each condition was quantified by micro-computed tomography. The 3D organotypic marrow explant culture resulted in the greatest level of ossification with plate-like bone formations (up to 5 mm in diameter and 0.24 mm in thickness). To evaluate the mimicry of the organotypic marrow explants to newly forming native bone tissue

  detailed compositional and morphological analyses were performed

  including characterization of the ossified matrix by histochemistry

  immunohistochemistry

  Raman microspectroscopy

  energy dispersive X-ray spectroscopy

  backscattered electron microscopy

  and micromechanical tests. The results indicated that the 3D organotypic marrow explant culture model mimics newly forming native bone tissue in terms of the characteristics studied. Therefore

  this platform holds significant potential to be used as a model of osteogenesis

  offering an alternative to in vitro monolayer cultures and in vivo animal models.

  A Scaffold-Free Multicellular Three-Dimensional In Vitro Model of Osteogenesis

  Rasim O. Güldiken

  Müge Türkaydın

  Microscale hydrogels find widespread applications in medicine and biology

  e.g.

  as building blocks for tissue engineering and regenerative medicine. In these applications

  these microgels are assembled to fabricate large complex 3D constructs. The success of this approach requires non-destructive and high throughput assembly of the microgels. Although various assembly methods have been developed based on modifying interfaces

  and using microfluidics

  so far

  none of the available assembly technologies have shown the ability to assemble microgels using non-invasive fields rapidly within seconds in an efficient way. Acoustics has been widely used in biomedical arena to manipulate droplets

  cells and biomolecules. In this study

  we developed a simple

  non-invasive acoustic assembler for cell-encapsulating microgels with maintained cell viability (>93%). We assessed the assembler for both microbeads (with diameter of 50 μm and 100 μm) and microgels of different sizes and shapes (e.g.

  cubes

  lock-and-key shapes

  tetris

  saw) in microdroplets (with volume of 10 μL

  20 μL

  40 μL

  80 μL). The microgels were assembled in seconds in a non-invasive manner. These results indicate that the developed acoustic approach could become an enabling biotechnology tool for tissue engineering

  regenerative medicine

  pharmacology studies and high throughput screening applications.

  The assembly of cell-encapsulating microscale hydrogels using acoustic waves

  Shuqi Wang

  Efficient on-chip isolation of HIV subtypes

  Joshua Gargac