Tissue Engineering Research OverviewTissue engineering is an emerging interdisciplinary field which applies the principles of biology and engineering to the development of viable substitutes which restore, maintain, or improve the function of human tissues. This form of therapy differs from standard drug therapy in that the engineered tissue becomes integrated within the patient, affording a potentially permanent and specific cure of the disease state.
A large number of Americans suffer organ and tissue loss every year from accidents, birth defects, hereditary disorders, conditions and diseases. Improved understanding of biological processes holds promise for the development of new classes of biomaterials, polymers diagnostic and analytical reagents.
Tissue engineering integrates discoveries from biochemistry, cell and molecular biology, genetics, material science and biomedical engineering to produce innovative three dimensional composites having structure/function properties that can be used to either replace or correct damaged, missing or poorly functioning components in living systems. In addition, this emerging technology can be used to introduce better functioning components. The material components themselves may be processed from naturally occurring materials, processed from synthetic materials or a combination of these. Cellular and other biologic components may be added.
Tissue engineering faces the challenges in:
- Permanent versus biodegradable
- Optimal lifespan of scaffold or product
- Degradation products
- Optimal geometry/architecture/composition
- Surface features (and how to modify them e.g., biomimetics)
- Role of surface features in biointegration
- Biomechanical characteristics
Faculty Research Interests
Health Sciences Tower 16-060
Summary : Our laboratory focuses on the design and development of bioactive peptides and 3-D complex extracellular matrices (ECM) that will enhance soft tissue repair and regeneration. Peptides are assayed for biological activity in vitro and in vivo for their ability to protect tissue cells and organs from injury, stimulate tissue cell migration and proliferation and modulate stem cell and tissue cell differentiation. The ECM constructs tethered with bioactive peptides are analyzed for their physical, chemical and immunologic properties by such modalities as goniometry for hydrophilicity, static and dynamic stress and strain for viscolastic material properties, atomic force microscopy for Young's elastic moduli and surface topography; HPLC, mass spectroscopy, gel permeation chromatography and gel electrophoresis for chemical analysis; and fluorescence immunoassays for immunologic epitope mapping. In addition, cell interactions with the 3-D ECM constructs are examined at the transcriptional, protein and functional level as judged by real-time PCR, DNA microarray analyses, Western blots, proteomics, quantitative fluorescence microscopy, and cell viability, migration and proliferation assays. Special in vitro systems have been created to quantify sprout angiogenesis, epithelial sheet migration and neurite axon extension. Bioactive peptides and engineered ECM containing peptide biomimetics will also be tested in a variety of animal models and hopefully enter into clinical trials. This robust array of bioactive peptides and 3-D ECM constructs will provide new therapies for soft tissue injury and disease.
Chemistry - 479
Summary : I am interested in understanding the structural and morphological development and manipulation of complex polymer systems during preparation and processing in real time. The focus of my research projects is the design, preparation, characterization and application of nanostructured soft condensed materials, such as fibers (one-dimensional orientation), films (two-dimensional orientation) and bulk material systems (three-dimensional orientation), through precise control of molecular architecture and physical interactions including crystallization, molecular level mixing, deformation and flow. My particular interests in biomedical applications include the use nanostructured biodgredation materials for drug release and tissue engineering.
Bioengineering Building - Room 213
Summary : Research in this laboratory focuses on the identification of precise parameters that define skeletal tissue quantity and quality and their perturbation to applied physical stimuli. To this end, state of the art imaging techniques (e.g., microCT or synchrotron infrared spectroscopy) are combined with molecular (e.g., RT-PCR), genetic (e.g., QTL), and engineering techniques (e.g., finite element modeling) to determine genes, molecules, forces, as well as chemical and structural matrix properties. An example for a recent study includes the demonstration that extremely small amplitude oscillatory motions (~ 100µm), inducing negligible deformation in the matrix, can serve as an anabolic stimulus to osteoblasts in vivo, producing a structure that is mechanical stronger and more efficient to withstand forces. Recent results also indicate that there is not only a genetic basis for bone architecture, but also that the sensitivity of bone tissue to both anabolic and catabolic stimuli is influenced by subtle genetic variations. The identification of the specific chromosomal regions that modulate this differential sensitivity is in progress. Clinically, our studies may lead to the development of effective prophylaxes and interventions for osteoporosis, without side-effects and tailored towards the genetic make-up of an individual.
Bioengineering Building - Room 215
Summary : Early diagnostic of osteoporosis allows for accurate prediction of fracture risk and effective options for early treatment of the bone disease. A new ultrasound technology, based on focused transmission and reception of the acoustic signal, has been developed by Dr. Qin and his team which represents the early stages of development of a unique diagnostic tool for the measure of both bone quantity (density) and quality (strength). These data show a strong correlation between non-invasive ultrasonic prediction and micro-CT determined bone mineral density (r>0.9), and significant correlation between ultrasound and bone stiffness (r>0.8). Considering the ease of use, the non-invasive, non-radiation based signal, and the accuracy of the device, this work opens an entirely new avenue for the early diagnosis of metabolic bone diseases.
Bioengineering Building - Room 101
Associate Professor & Graduate Program Director
Summary : The goal of our lab is to 1) develop a biomimetic three-dimensional tissue engineering scaffolds that promotes microvascular blood vessel growth and 2) elucidate mechanisms that induce cardiovascular disease responses. The need for new tissue engineering scaffolds that promote microvascular growth arises due to diffusion limitations through biological tissue, which at best is approximately 100 microns. With a method to fabricate patent vascular networks ex vivo, it is possible that large scale tissue engineering applications can be realized or the healing of chronic wounds can be accelerated. Our work has identified a number of viable scaffolds that can promote vascular network growth. Additionally, more recent work has focused on identifying scaffold fabrication techniques that can form viable scaffolds for microvascular applications. Cardiovascular diseases remain the leading cause of death in the Western world. Due to this, it is salient that an understanding of disease progression is found. We aim to understand how combinations of cardiovascular disease risk factors interact to induce, accelerate, enhance or inhibit cardiovascular disease processes. Our main focus is on advanced glycation end products (diabetes), tobacco smoke and disturbed wall shear stress. We focus on platelets, endothelial cells and their interactions for all projects in our lab.
Bioengineering Building - Room 217A
Distinguished Professor & Chair
Summary : Encouraging results show that the application of extremely low level strains to animals and humans will increase bone formation, and thus may represent the much sought after "anabolic" stimulus in bone. More than 15 years of research into non-invasive, non-pharmacological intervention to control osteoporosis, was referenced in Dr. Rubin's paper published in the journal Nature (August 9, 2001; 412:603-604). Dr. Rubin's studies suggest that gentle vibrations on a regular basis will help strengthen the bones in osteoporosis sufferers and increase bone formation. In his study, adult female sheep treated with gentle vibration to their hind legs for 20 minutes daily showed almost 35% more bone density. Clinical trials have been completed on post-menopausal women, children with cerebral palsy, and young women with osteoporosis, all with encouraging results. In expanding the research platform into other physiologic systems, current work demonstrates that these low-level signals influence mesenchymal stem cell differentiation, such that their path to adipocytes is suppressed, and markedly reduces adipose tissue.
Bioengineering Building - Room 115
Summary : Our laboratory seeks to integrate advances in nanoscience and technology with the biological sciences and clinical medicine to achieve significant advances in simultaneous molecular diagnostics and therapeutics (theragnosis), drug delivery, and bioengineering. Towards these ends, our research interests involve a multidisciplinary approach for the development of functional (electronic, optical, magnetic, or structural) bionanosystems as contrast agents for molecular imaging, as carriers for drug delivery, and as structural scaffolds for tissue engineering. Our current projects capitalize on the unique properties of carbon nanobiomaterials to develop a) advanced contrast agents (CAs) for molecular magnetic resonance imaging (MRI), b) nanocomposites to improve the physical and biological (osteoconduction and osteoinduction) properties of polymer scaffolds for bone tissue engineering and c) non-viral vectors for gene transfection. We have exploited the potential of Gd-based carbon nanostructures: Gd@C60 metallofullerenes (gadofullerenes) and Gd@Ultrashort-tubes (gadonanotubes) as a new generation of advanced CAs for MRI and shown them to have efficacies up to 100 times greater than current clinical CAs. Our recent studies show that they are particularly well suited for passive (magnetic labels for cellular MRI) and active (pH sensitive probes for cancer detection) MRI-based Molecular Imaging. Single-walled carbon nanotubes (SWNTs) have been proposed as the ideal foundation for the next generation of materials due to their excellent mechanical properties. We have dispersed SWNTs and ultra short SWNTs into fumarate-based polymers to form nanocomposite scaffolds that exhibit mechanical properties far superior to the polymers alone and are osteoconductive as well osteoinductive. Our research work involves material synthesis techniques, physico-chemical characterization techniques, tissue culture and in vivo studies.
Cold Spring Harbor Labs
Summary : Two challenges in cancer biology guide my work: first, how do tumors become addicted to certain gene products, and second, how do tumors develop resistance to anti-cancer drugs. I focus on the epidermal growth factor receptor (EGFR), which is both addictive when mutated and a common source of drug resistance.
NIH National Human Genome Research Institute
Summary : The Organic Acid Research Section (OARS) studies a group of inborn errors of metabolism, the hereditary methylmalonic acidemias (MMA), and disorders of intracellular cobalamin metabolism. What has remained both perplexing and challenging is the wide spectrum of clinical phenotypes presented by the patients and the generally untreatable nature of many of the complications they display, such as renal disease in patients with isolated MMA and progressive visual deterioration in those with cobalamin C (cblC) deficiency.
Bioengineering Building - Room 109
Summary : Cardiovascular disease is the leading cause of death in the United Sates, and coronary artery disease is the most common type of cardiovascular disease. Shear stress induced by blood flow plays an important role in the initiation and development of atherosclerosis, the major reason for coronary artery disease. Circulating platelets and vascular endothelial cells are very sensitive to their mechanical environment; any change can affect their functions and interactions significantly. My major research interest is to investigate how altered blood flow and stress distribution affect platelet and endothelial cell behavior and lead to cardiovascular disease initiation. Computational fluid dynamics modeling, along with in vitro and ex vivo experiments, are carried out to study platelet and endothelial cell responses under physiologically relevant dynamic conditions. Biomarkers associated with platelet and endothelial cell activation are of special interest to us. We also work on numerical models to describe platelet coagulation kinetics and platelet adhesion to injured blood vessel wall under dynamic flow conditions.