Past Bone Seminars

Spring 2004 Series

___February 2004___

Speaker: John L. Ricci PhD, Associate Professor, Department of Biomaterials and Biomimetics, New York University College of Dentistry
Topic: Tissue Response to Scaffold Architectural Features Across Length Scales

Dr. Ricci’s Research Interests: Active areas of research involve cell and tissue response to permanent and resorbable biomaterials and implants. Development of experimental models for the controlled investigation of bone and soft tissue response to biomaterials, and investigation and development of technologies for enhancing tissue repair, regeneration, and tissue integration of implantable biomedical devices.

Abstract
Cell and tissue response to any type of implantable scaffold or biomaterial can be controlled by a complex combination of the chemical composition, surface microstructure, macrostructure, engineering design, and control of the functional environment of the implant. If engineered properly, the biomaterial scaffold and biological tissue can become a fully integrated composite. In order to optimize the integration of implant and tissue we must understand biologic response across length scales from nanostructural range to millimeter range, and utilize material fabrication techniques that allow us to control the structure of the biomaterial surface in these same ranges. We divide these scales into four functional ranges. The nanostructural range (submicron range) represents surface chemistry, the size scale in which the biomaterial or scaffold surface interacts on the molecular level with adsorbed biomolecules such as proteins and extracellular matrix components. The microstructural range (from ~1-20µm) represents the range in which the surface interacts with the cell surface and directs cell attachment, cell shape, migration, and spreading. The mesostructural range (from ~20-1000µm) represents the range in which the scaffold structure interacts with the tissue as a combination of cells, extracellular matrix, and vessels. Scaffold design versus nutrient diffusion now becomes a consideration, as does pore and strut dimension versus the sizes of ingrowing structures such as blood vessels and bone trabeculae. The fourth and largest range, the macrostructural range (from 1-102mm) represents the range in which the implant/scaffold interacts with anatomic structures such as layers of skin and subcutaneous tissue, or muscles, bone, tendon, or organs.

Our recent research has utilized advances in materials fabrication and surface modification technologies to superimposed combinations of defined meso- and microgeometries onto materials with proven surface chemistry (nanostructure) to create permanent and resorbable bone implants and scaffolds. Over the last few years we have developed dental implants with laser-machined, controlled surface microgeometries that are now in clinical use and are exhibiting excellent clinical results. We are also investigating 3-D printed ceramic and polymeric bone replacement structures that utilize controlled mesostructure and microstructure to enhance bone ingrowth and integration. These are intended for use as bone graft replacement materials. The current status of these projects will be discussed along with future implications.

___March 2004___

Speaker: Liyun Wang PhD, Postdoctoral Research Fellow, Department of Orthopaedics, Mount Sinai School of Medicine, New York, NY
Topic: In Situ Study of Solute Transport in the Bone Lacunar-Canalicular System Using Fluorescence Recovery after Photobleaching

Dr. Wang’s Research Interests: Studying transport phenomena and cellular responses to physiological stimuli (e.g., mechanical loading) in biological and engineered porous tissues using experimental, mathematical, and computational approaches

Abstract

Osteocytes are the most numerous cells in bone and participate in many physiologically important functions including mechanotransduction, damage repair via targeted remodeling, and calcium homeostasis. As osteocytes are completely encased in the mineralized matrix of bone, their ability to survive and function is entirely dependent on mass transport through the small interconnecting channels (~200 nm wide) of the lacunar-canalicular system. Transport of solutes (nutrients and bioactive molecules) through the lacunar-canalicular system occurs by diffusion and convection. However, attempts to study solute transport mechanisms in the lacunar-canalicular system have been limited principally to either computational approaches or experimental approaches based on examining tracer localization/movement in tissue sections or blocks. These have been unable to elucidate the specifics of local factors influencing transport (molecular size, local permeability) or to unravel the complexities of diffusion versus convection in vivo. To this end, we developed a novel imaging approach that allows real time visualization and measurement of tracer transport via the lacunar-canalicular system in intact bones. We adapted Fluorescence Recovery After Photobleaching (FRAP), a technique that has been used for studying molecule translocation on cell membrane, inside cellular compartments, and in tumor tissues, to study tracer diffusion in intact mouse tibia immediately post-mortem. To obtain quantitative data on tracer diffusivity, we developed a two-compartment model to describe tracer influx to the photobleached lacuna following Fick’s law. Our current studies are focused in understanding the relative contributions of diffusion, convection due to vascular pressure and convection due to mechanical loading in solute transport in bone, with the long term goal of understanding osteocyte functions and cellular responses to physiological challenges.

___April 2004 ___

The April 2004 Bone Seminar was cancelled due to incredibly inclement weather all along the Eastern seaboard. The speaker, Janet Rubin MD (who was rained in at the Atlanta airport), was rescheduled and gave her presentation in November 2004.

___May 2004___

Speaker: Sharon Swartz PhD, Associate Professor of Biology, Department of Ecology and Evolutionary Biology, Brown University, Providence, RI
Title: “Data Mining” Evolution's Bone Design Experiments

Dr. Swartz's Research Interests: Mechanics and aerodynamics of bat flight, including specific roles of wing skin and bone mechanical properties and structural design; scale effects in skeletal architecture; evolution of mammalian locomotion and skeletal diversity

Abstract

One fundamental goal of bone biology is to understand the determinants of the many levels bone structure, from the molecular to the organ system. In particular, insight into the role of mechanical loading in dictating bone architecture is critical to both improving human health and discerning the evolutionary history of the vertebrate skeleton. Evolutionary biologists have taken advantage of the rich findings of basic research in bone biology to improve our understanding of the evolution of the skeletal system, particularly for mammals. In turn, I believe evolutionary biologists can contribute to basic bone biology by drawing on the enormous natural diversity of skeletal form and function produced by millions of years of evolution. The perspectives of comparative/historical biology can be employed to test hypotheses concerning the relationships between the mechanics and architecture of bone, and to develop new hypotheses for future experimental work. Implicitly or explicitly, our starting point is that any theory that relates mechanical load to skeletal structure should be applicable not only to humans but also to related species - perhaps to other apes, other primates, other mammals, other homeothermic vertebrates. Comparisons of bone form among species that differ greatly in their locomotor behavior and hence typical bone loading regimes can therefore be used to test how broadly a particular explanation extends. One case that may illuminate our understanding of the skeleton is that of bats, one of the most evolutionarily successful groups of mammals. The function and morphology of the upper limb (wing) skeleton of bats shares both similarities to and differences from that of other mammals. The bones of the bat wing rarely experience impact loads of any kind, and instead are subjected to large aerodynamic forces distributed to the skeleton by mechanically complex wing membrane skin. Both magnitude and distribution of bone strains differ between the bones of bat limbs and those of other mammals, as do a number of features of the form and material composition of bat wing bones. The implications of our observations on the skeletons of bats and other vertebrates for understanding bone as a mechanically responsive tissue will be explored.