R. Imer

Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy

The pathological changes in osteoarthritis--a degenerative joint disease prevalent among older people--start at the molecular scale and spread to the higher levels of the architecture of articular cartilage to cause progressive and irreversible structural and functional damage. At present, there are no treatments to cure or attenuate the degradation of cartilage. Early detection and the ability to monitor the progression of osteoarthritis are therefore important for developing effective therapies. Here, we show that indentation-type atomic force microscopy can monitor age-related morphological and biomechanical changes in the hips of normal and osteoarthritic mice. Early damage in the cartilage of osteoarthritic patients undergoing hip or knee replacements could similarly be detected using this method. Changes due to aging and osteoarthritis are clearly depicted at the nanometre scale well before morphological changes can be observed using current diagnostic methods. Indentation-type atomic force microscopy may potentially be developed into a minimally invasive arthroscopic tool to diagnose the early onset of osteoarthritis in situ.

Development of Atomic Force Microscope for Arthroscopic Knee Cartilage Inspection

A recent study, based on ex vivo unconfined compression testing of normal, diseased, and enzymatically altered cartilage, revealed that a scanning force microscope (SFM), used as a nano-intender, is sensitive enough to enable measurement of alterations in the biomechanical properties of cartilage. Based on these ex vivo measurements, we have designed a quantitative diagnosis tool, the scanning force arthroscope (SFA), able to perform in vivo measurements during a standard arthroscopic procedure. For stabilizing and positioning the instrument relative to the surface under investigation, a pneumatic system has been developed. A segmented piezoelectric tube was used to perform the indentation displacement, and a pyramidal nanometer-scale silicon tip mounted on a cantilever with an integrated deflection sensor measured the biomechanical properties of cartilage. Mechanical means were designed to protect the fragile cantilever during the insertion of the instrument into the knee joint. The stability of the pneumatic stage was checked with a prototype SFA. In a series of tests, load-displacement curves were recorded in a knee phantom and, more recently, in a pigs leg.

ASSESSMENT OF EARLY OSTEOARTHRITIS IN HUMAN KNEE CARTILAGE BY SCANNING FORCE MICROSCOPY

1. Department of Biophysical and Electronic Engineering, University of Genova, Italy; 2. M.E. Muller Institute for Structural Biology, Biozentrum University of Basel, Switzerland; 3. Department of Orthopaedic Surgery & Traumatology, Kantonsspital, Bruderholz/Basel, Switzerland; 4. Laboratory for Tissue Engineering, Department of Surgery & Research, University Hospital of Basel, Switzerland; 5. Center for Microscopy, University of Basel, Switzerland; 6. Institute of Microtechnology, University of Neuchâtel, Switzerland.