Biomaterials and Chemical Biology of Regeneration

T. Gabriel Chu, DDS, PhD
Eric C. Long, PhD
Christoph A. Naumann, PhD
Hiroki Yokota, PhD
Dong Xie, PhD

T. Gabriel Chu, DDS, PhD

Positions

• Assistant Professor

Address
Dept. of Biomedical Engineering
School of Engineering and Technology
Indiana University-Purdue University Indianapolis
1120 South Dr. Rm.115L
Indianapolis, IN 46202

Phone: (317) 278-8716
Fax: (317) 278-9568
Email: tgchu@iupui.edu

Research Interests

Each year, approximately 6 million fractures occur in the United States which requires a total of 9 million physician visits and causes a loss of more than 36 million work days (American Academy of Orthopaedic Surgeon). One particular challenging condition that fracture can leave with the patient is segmental defects. Large segmental defects are often hard to manage and require multi-phase surgery to restore sufficient function and union. Current treatment options include autografts, allografts, and distraction osteogenesis. Though these treatments have brought forth clinical successes, they are still with considerable limitations. To overcome the limitations in these treatment options, researchers are exploring for new treatment methodologies. In our laboratory, we are investigating the use of rapid prototyping technique for manufacturing biodegradable, load-bearing bone tissue engineering scaffolds, and the in vivo evaluation of such scaffolds.

Recent Publications

• Chu TM, Warden SJ, Turner CH, Stewart RL. Segmental bone regeneration using a load-bearing biodegradable carrier of bone morphogenetic protein-2. Biomaterials. 2007 Jan;28(3):459-467. Epub 2006 Sep 25. PMID: 16996588 [PubMed - as supplied by publisher]
• Metz J, Gonnerman K, Chu A, Chu TM. Effect of crosslinking density on swelling and mechanical properties of PEGDA400/PCLTMA900 hydrogels. Biomed Sci Instrum. 2006;42:389-94. PMID: 16817639 [PubMed - indexed for MEDLINE]
• Metz J, Sargent P, Chu TM. Bovine albumin release and degradation analysis of dicalcium phosphate dihydrate cement.Biomed Sci Instrum. 2006;42:296-301. PMID: 16817624 [PubMed - indexed for MEDLINE]
• Howk D, Chu TM. Design variables for mechanical properties of bone tissue scaffolds.Biomed Sci Instrum. 2006;42:278-83. PMID: 16817621 [PubMed - indexed for MEDLINE]
• Gonnerman KN, Brown LS, Chu TM. Effects of growth factors on cell migration and alkaline phosphatase release.Biomed Sci Instrum. 2006;42:60-5. PMID: 16817586 [PubMed - indexed for MEDLINE]

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Eric C. Long, PhD

Position

• Professor & Associate Chair, Chemistry

Address
Department of Chemistry
School of Science
Indiana University-Purdue University Indianapolis
402 N. Blackford Street, LD 326
Indianapolis, IN 46202-3274

Phone: (317) 274-6872
Fax: (317) 274-4701
E-mail: long@chem.iupui.edu

Research Interests

Intense interest in the design, synthesis and study of DNA and RNA binding agents is based on the ability of such compounds to act as anticancer drugs, nucleic acid structural probes, and models to understand the fundamental molecular recognition of these vital biopolymers. In this general area, our laboratory is engaged in two main research directions: (1) the synthesis and investigation of metal complexes with peptide-based ligands, i.e., "metallopeptides" and (2) the development and application of a high-throughput (HT), high-resolution (HR) strategy to rapidly determine the structures of DNA-bound ligands.

In the first area, we synthesize peptide ligands derived from the basic Gly-Gly-His tripeptide, e.g., Arg-Gly-His or Lys-Gly-His, etc., to generate metallopeptides of Cu2+, Ni2+, or Co3+ that contain the same chemical functional groups, such as guanidinium, amino, and amide moieties, employed by proteins or anti-tumor natural products for the selective recognition of DNA and RNA. In these systems, the metal center imparts nucleic acid cleavage activity and a well-defined 3-dimensional structure to the peptide that otherwise lacks these attributes. Our goal is to understand how amino acids within the three-dimensional constraints imposed by a metal center can be used to selectively and efficiently target nucleic acids, information central to increasing our understanding of drug- and protein-nucleic acid recognition phenomena. Further insight derived from these studies, such as particular spatial arrangements of chemical functional groups, and the differential activities of the diastereomeric metallopeptides that are often formed, could be used in the future rational design of DNA-interactive agents.

In our second area of current research, in collaboration with Prof. Millie Georgiadis, Department of Biochemistry & Molecular Biology, we are developing a high-throughput, high-resolution (HT-HR) strategy to expedite the investigation of DNA binding compounds. In this strategy, we make use of high-throughput screens to determine the precise site-selectivity of an unknown DNA binding agent followed by a host-guest crystallization approach to determine high-resolution information. Importantly, this strategy can yield detailed information about a DNA binding compound within days of the onset of study because crystallization is rapid while, typically, such investigations require months, or even years to generate useful high resolution data. In conjunction with this project we are synthesizing libraries of DNA binding compounds that can be screened for particular properties of biomedical relevance though our HT-HR strategy.

Recent Publications

• Murcia, M. J.; Shaw, D. L.; Woodruff, H.; Naumann, C. A.; Young, B. A.; and Long, E. C. "Facile sonochemical synthesis of highly luminescent ZnS-shelled CdSe quantum dots" Chemistry of Materials 2006, 18, 2219-2225.
• Goodwin, K. D.; Lewis, M. A.; Tanious, F. A.; Tidwell, R. R.; Wilson, W. D.; Georgiadis, M. M.; and Long, E. C. "A high-throughput, high-resolution strategy for the study of site-selective DNA binding agents: Analysis of a 'highly twisted' benzimidazole-diamidine" Journal of the American Chemical Society 2006 , 128, 7846-7854.
• Fang, Y.-Y.; Lipkowitz, K. B.; and Long, E. C. "Molecular dynamics simulations of the orientation of Ni(II)•Gly-Gly-His and Ni(II)•Arg-Gly-His metallopeptide-DNA Association" Journal of Chemical Theory & Computation 2006 , 2, published on web 07/29/06.
• Fang, Y.-Y.; Claussen, C. A.; Lipkowitz, K. B.; and Long, E. C. "Diastereoselective DNA cleavage recognition by Ni(II)•Gly-Gly-His-derived metallopeptides" Journal of the American Chemical Society, 2006, 128, 3198-3207. (pdf file)
• Lewis, M. A. and Long, E. C. "Fluorescent intercalator displacement analyses of DNA binding by the peptide-derived natural products netropsin, actinomycin, and bleomycin" Bioorganic & Medicinal Chemistry 2006, 14, 3481-3490. (pdf file)

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Christoph A. Naumann, PhD

Position

• Associate Professor

Address
Department of Chemistry
School of Science
Indiana University-Purdue University Indianapolis
402 N. Blackford Street, LD 326
Indianapolis, IN 46202-3274

Phone: (317) 278-2512
Fax: (317) 274-4701
E-mail: naumann@chem.iupui.edu

Research Interests

Our first area of interest is the biofunctionalization of inorganic solids and polymeric materials with bioartificial membranes that mimic specific properties of native biomembranes. The biofunctionalization of substrates is of great practical and scientific interest because it not only opens a wide field for studying biochemical processes with surface-sensitive detection techniques but has also several technical applications such as biosensors or biomaterials. Our main goal is a fundamental understanding of the relationship between molecular design and functionality of bioartificial membranes on substrates. Specifically, we are monitoring the movement of single proteins and lipids within the 2-dimensional matrix of bioartificial membranes via single molecule fluorescence imaging microscopy. This will help explain of how the membrane properties are affected by the underlying substrate.

Our second research area has its focus on the structure-function relationship of biomaterials. Biomaterials are synthetic materials, which treat or replace any tissue, organ, or function of the body. The quality of a biomaterial depends on several factors including: its design, its properties, and its acceptance by the surrounding tissue (biocompatibility). One research interest has the goal to obtain a deeper understanding of how chemical and physical properties affect the biocompatibility of potential biomaterials. Our experiments will help develop biomaterials with novel surface properties.

Recent Publications

• Naumann, C. A., Prucker, O., Lehmann, T., Ruehe, J., Knoll, W., Frank, C. W. (2002) The Polymer-supported phospholipid bilayer: Tethering as a new approach toward substrate-membrane stabilization. Biomacromolecules 3, 27-35.
• Coffman, J. P., Naumann, C. A. (2002) Molecular weight dependence of viscoelastic properties in two-dimensional physical polymer networks of amphiphilic lipopolymer monolayers at the air-water interface. Macromolecules 35, 1835-1839.
• Ke, P. C., Naumann, C. A. (2001) Hindered diffusion in polymer-tethered phospholipid monolayers at the air-water interface: A single molecule fluorescence imaging study. Langmuir 17, 5076-5081.
• Ke, P. C., Naumann, C. A. (2001) Single molecule fluorescence imaging of phospholipid monolayers at the air-water interface. Langmuir 17, 3727-3733.
• Frank, C. W., Naumann, C. A., Knoll, W., Brooks, C. F., Fuller, G. G. (2001)Two-dimensional physical networks of lipopolymers at the air-water interface. Macromolecular Symposia 166, 1-12.

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Hiroki Yokota, PhD

Position

• Associate Professor

Address
Department of Biomedical Engineering
School of Engineering and Technology
Indiana University-Purdue University Indianapolis
723 W. Michigan St.
Indianapolis, IN 46202

Phone: (317) 274-2448
Fax: (317) 274-4567
Email: hyokota@iupui.edu

Research Interests

The major research focus in my lab is mechanotransduction of bone: how to elevate bone growth using mechanical loading. Bone is responsive to mechanical stimulations and it alters its growth rate and pattern depending on biophysical environments. Using cultured bone cells as well as mice and rabbits as model organisms, we investigate the mechanical conditions that effectively stimulate bone adaptation as well as healing of wounded bones. The research is multidisciplinary, encompassing techniques in biomechanics, molecular and cell biology, systems biology and engineering, and animal surgery. Specifically, our unique expertise includes development of custom-made mechanoelecrical devices with nanometric resolution, application of cutting-edge imaging and sensing techniques for measuring load-driven strain, molecular transport, and pressure modulation, and genome-wide gene expression analyses using biology-inspired computational algorithms such as genetic algorithms and ant algorithms.

Two particular projects are “molecular biology of osteoblast cells under strain-induced fluid flow,” and “development of a joint-loading modality for enhancing bone growth.” In the former project, we examine expression of mRNA and proteins involved in bone formation in response to physiologically relevant mechanical stimulations and identify a network of molecular interactions involved in mechanotransduction. In the latter project, we evaluate the effects of lateral loads applied to synovial joints such as a knee and an elbow on remodeling of long bones such as a tibia, a femur, and an ulna. This loading modality, named as joint loading, has a potential usage to prevent bone loss of the elderly and in the space age under microgravity.

Recent Publications

• Zhang P, Su Tanaka SM, Jiang H, Su M, and Yokota H (2006). Diaphyseal bone formation in murine tibiae in response to knee loading. J. Applied Physiology 100:1452-1459.
• Pidaparti RM, Murugesan K, and Yokota H (2006). Computational framework for nanoscale self-assembly of collagen fiber. J. Computational and Theoretical Nanoscience 3:1-6.
• Zhang P, Su M, Tanaka SM, and Yokota H (2006). Knee loading stimulates cortical bone formation in murine femurs. BMC Musculoskeletal Disorders 7:73.
• Liu Y, and Yokota H (2006). Artificial ants deposit pheromone to search for regulatory DNA elements. BMC Genomics 7:221.
• Su M, Jiang H, Zhang P, Liu Y, Wang, E Hsu A, and Yokota H (2006). Knee-loading modality drives molecular transport in mouse femur. Annals of Biomedical Engineering 34:1600-1606.

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Dong Xie, PhD

Positions

• Associate Professor, Department of Biomedical Engineering
• Associate Professor, Department of Surgery, School of Medicine

Address
Department of Biomedical Engineering
School of Engineering and Technology
Indiana University-Purdue University Indianapolis
723 W. Michigan St. SL 164G
Indianapolis, IN 46202

Phone: (317) 274-9748
Fax: (317) 278-2032
Email: dxie@iupui.edu

Research Interests

Dr. Xie works primarily in the area of advanced polymeric biomaterials. One major goal in this emerging field is to develop novel polymers and their composites for dental and orthopedic applications, which include hard tissue and soft tissue restorations. The second main goal in this field is to develop novel biodegradable polymer and composite systems for tissue engineering, which includes design and formulation of deliverable, in situ polymerizable and resorbable polymers as tissue scaffolds for soft and hard tissue regenerations. ??More recently, Dr. Xie has begun to work on regenerative medicine, specifically in the area of immune protection of cell or organ transplantations. He has initiated collaboration with Dr. Mark Pescovitz, Director of Organ Transplant at Indiana University Medical Center on pancreatic islet transplantations. The goal of this research is to engineer tissue compatible polymers to pancreatic islets to completely diminish all the detrimental immune and complement-mediated reactions that may occur during islet allo- or xenotransplantations and to prevent loss of islet mass, which will dramatically impact millions of patients in need of pancreatic islet transplantation.

Recent Publications

• Xie, D., Smyth, C.A., Eckstein, C., Bilbao, G., Mays , J., Eckhoff, D.E., Contreras, J.L. Cytoprotection of PEG-modified adult porcine pancreatic islets for improved xenotransplantation, Biomaterials , 2005; 26(4):403-412.
• Xie, D., Chung, I-D., Wang, G., Feng, D., Mays, J., Synthesis, formulation and evaluation of novel zinc-calcium phosphate-based adhesive resin composite cement, Eur. Polym. J ., 2004; 40(8):1723-1731.
• Xie, D. , Chung, I-D., Wu, W., Lemons, J., Puckett, A., and Mays, J. An amino acid modified and non-HEMA containing glass-ionomer cement, Biomaterials, 2004; 25(10):1825-1830.
• Xie, D. , Chung, I-D., Wu, W., and Mays , J., Synthesis and evaluation of HEMA-free glass-ionomer cements for dental applications, Dent. Mater., 2004; 20:470-478.
• Xie, D. , Wu, W., Puckett, A., Farmer, B., and Mays , J., Novel Resin Modified Glass Ionomer Cements with Improved Flexural Strength and Ease of Handling, Eur. Polym. J ., 2004; 40(2):343-351.

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