2013 Orthopaedic Research Society (ORS) Posters
Prof. Wallace will presenting posters numbers 0611 and 1378 at ORS on the "Effects of Hydration on Nanoscale Morphology and Mechanics of Individual Type I Collagen Fibrils in the Brtl Mouse Model of Osteogenesis Imperfecta" and the "Increased Tendon Fiber Modulus and Strength and Decreased Failure Strain in a Rat Model of Type 2 Diabetes."
Max will presenting poster number 0713 on "Alterations in Diabetic Bone Revealed by Co-localized
Raman and Reference Point Indentation."
Notable Research Projects in the BBML
A variety of research endeavors are currently underway in the BBML. To read more about any of these general areas, click on the corresponding section title.
General Introduction to Bone: Collagen and Mineral
As a tissue and organ, bone serves vital structural and metabolic roles in the body. Bone is hierarchical, having structural elements that exist independently at length scales ranging over 9-10 orders of magnitude from the molecular level to the organ level. Bone is primarily a two-phase composite material composed of a flexible collagen matrix which is impregnated with and surrounded by a stiffer, stronger, reinforcing mineral. The combination of strength, stiffness and toughness that are mechanical characteristics of bone as a tissue are initially derived from the interaction between these nanoscale constituents. Bone balances strength and toughness with minimal mass while contending with the constant structural and metabolic demands of the body.
Introduction to Atomic Force Microscopy
As opposed to traditional microscopes which focus light or electrons on a sample to produce an image, atomic force microscopy (AFM) works by dragging a sharpened probe over the surface and using interactions between the surface and probe to build a map of the sample's topography. In essence, AFM acts like a nanoscale phonograph or record player. AFM is relatively inexpensive and simple to perform. It is a high-resolution imaging modality which is less-destructive than either transmission electron microscopy (TEM) or scanning electron microscopy (SEM), techniques which researchers have traditionally relied upon to probe the nanoscale properties of materials such as bone. Samples imaged using AFM can remain intact and can be imaged in air or fluid, at room temperature or under culture conditions, implying that measured properties are characteristics of the sample and less likely artifacts of processing or imaging. In addition, the AFM probe can be used to extract nanoscale mechanical properties (both in terms of the forces and physical size of material that is probed) by scratching, indenting, pushing or pulling on the sample.
Applications of Atomic Force Microscopy for the Assessment of Nanoscale Morphological and Mechanical Properties of Collagen-Based Tissues
Over the past few years, our lab has focused on applying AFM-based imaging and mechanical probing to the assessment of tissues including bone, dentin and tendon. These studies have yielded new and exciting information about fundamental characteristics of the ultrastructure of collagen-based tissues. In addition, disease-induced changes in these tissues have been uncovered.
Diseases-Induced Changes in the Extracellular Matrix of Bone and Other Collagen-Based Tissues
One of our key research thrusts is focused on examining possible mechanisms of diseases which impact bone and other collagen-based tissues through changes in extracellular matrix structure and function. Despite the importance of skeletal health to overall health, there is a critical lack of understanding of how the fundamental constituents of bone (collagen and mineral) impact whole bone mechanical integrity. There is also limited knowledge of how perturbations to these constituents occurring with disease alter bone's mechanical competence. Specific diseases of interest include the genetic disease Osteogenesis Imperfecta (OI), ovariectomy-induced estrogen depletion and Osteoporosis (OVX) and pharmacologically-induced lathyrism. We are examining bones, teeth, tendons and skin from various mouse models of these disease using multiple imaging and mechanical testing techniques spanning several relevant levels of tissue hierarchies. This in-depth analysis will allow us to correlate genotype with structural changes in collagen while leading to a better understanding of structure/function relationships in Type I collagen-based tissues.
Mechanical Stimulation of Bone: Exercise and Loading
Another primary research focus of the lab is the study of how mechanical stimuli affect bone. We aim to understand how mechanical stimuli, either directly applied via the mechanical loading of specific limbs or through exercise on the treadmill, play a role in formation, organization and maintenance of bone at the nanoscale and how this correlates with observations at other length scales.
Collaborative Studies With the Indiana University School of Medicine and Purdue University
Collaborations with Dr. David Burr and Dr. Matthew Allen from the Indiana University School of Medicine are underway. In these collaborative efforts, we have probed how the Osteoporosis drug Raloxifene affects the nanostructure of collagen. Other studies are aimed at trying to uncover the mechanism for altered mechanical properties in the bones of a diabetic rat model (ZDSD). An additional recent collaboration with Dr. Sherry Voytik-Harbin from the Department of Biomedical Engineering at Purdue University is aimed at understanding the link between nanoscale morphology in Type I collagen fibrils and intra/inter-molecular cross links.