Originally Published MDDI August 2002
R&D DIGEST
Probing Cartilage at Nanoscale Levels
) |
| Studies by MIT professors Christine Ortiz and Alan Grodzinsky could lead to the development of improved bone implants. (click to enlarge) |
Cartilage is a remarkably complex biocomposite material that exhibits outstanding compressive stiffness, toughness, strength, resiliency, and shock absorption. Scientists have long explored the processes that cause these properties to degrade with age and with certain debilitating diseases. Researchers at the Massachusetts Institute of Technology (MIT) Center for Biomedical Engineering (Cambridge, MA) now believe that they may have new tools for revealing the secrets of cartilage function.
Cartilage is composed of a matrix material and cells capable of producing that matrix. The matrix itself is made up of a collagen mesh and a gel composed of proteoglycan. The structure of the proteoglycan molecules resembles circular brushes. Based on measurements at the tissue level, the MIT researchers speculated that "these molecules play an extremely important role in cartilage function because of electrical repulsive interactions between the brush 'bristles,' or glycosaminoglycan (GAG) chains," says Alan Grodzinsky, director of the center.
Studies of these molecular bristles using novel nanoscale mechanical measurements are giving the researchers new insights into cartilage function. The research may also help in characterizing other components of cartilage material. A molecular force probe (MFP), with a tip radius of about 25 nm, was used to measure the forces between the tip and the surface of a bristled polymer as the tip was moved up and down at a constant rate. Says Grodzinsky, "To have a window into how these GAG molecules deform just hasn't been done before in the cartilage field." The results of the initial experiments have helped quantify the contribution of various forces between the bristles.
According to Christine Ortiz, PhD, assistant professor in MIT's Department of Materials Science and Engineering, "Basically, these experiments could have been done with other commercially available atomic force microscopes (AFMs). However, the MFP offers a number of advantages over these instruments." Ortiz explains that the MFP is based loosely on atomic force microscopy—including a micromachined flexible cantilever with a sharp tip used as a force transducer. "However, many improvements in the components, the design, and the software have been made relative to standard commercially available AFMs, specifically with high-resolution force measurements in mind," Ortiz says. "The MFP gives a bottom-up view of the tip and sample through a transparent sample support such as a microscope slide or a petri dish, with a video microscope. The fluid cell is an open design, allowing for easy sample mounting and changes."
Ortiz says the probe offers a number of significant capabilities. Among these are precise and accurate cantilever force, transducer-spring constant calibration, and ease of working in fluid physiological conditions. The system also provides a high-resolution strain gauge sensored z-axis that quantifies the distance between the cantilever and the sample accurately, thus eliminating errors caused by piezohysteresis and other conditions. In addition, use of low-coherence light and diffraction-limited, high-numerical-aperture laser optics minimizes interference reflections.
The project is now being expanded "to look at the forces between the other load-bearing molecules of cartilage to help understand the role of each," says Ortiz. The basic techniques used are also being applied to studies involving industrially important polymers, drug particles, bone and bone-implant materials, and interactions between membrane proteins and foreign bodies. Ortiz adds, "We are currently using the same techniques to investigate all of these areas. For example, we do experiments to measure the nanoscale interactions between a probe tip coated with blood plasma proteins (human serum albumin) and a synthetic polymer, poly(ethylene oxide), which is commonly used for coating biomedical implants, in order to investigate the molecular origins of biocompatibility."
Ortiz explains that being able to assess the force between drug particles is critical to their processing and ultimately affects the uniformity of dosage. "Our work on bone and bone-implant materials (e.g., hydroxyapatite) involves studies of the molecular aspects of deformation and fracture, their nanoscale mechanical properties, and how they interact with bone proteins, cells, and other macromolecules such as glycosaminoglycans," she says. "This ultimately will lead to a more fundamental understanding of how bone-implant materials are integrated into the body and what properties are needed for better implants."
Copyright ©2002 Medical Device & Diagnostic Industry
