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AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsR. Smith, Dennis Carter, David Schurman
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A method for in vivo, ex vivo and in vitro regeneration of cartilage and collagen. In vivo, ex vivo and in vitro regeneration and de novo formation of articular cartilage and collagen by intermittently applied hydrostatic pressure. The application of external interval loading consisting of repeated periods of applied hydrostatic pressure followed and interrupted by periods of recovery. The application of the intermittent hydrostatic pressure at physiological levels 5-10 MPA for an interval of 4 hours followed by a recovery period up to about 20 hours, said pressure applied to the cartilage cells in vitro, explants of cartilage ex vivo and in vivo to cartilage that remains intact within the joint space of diarthrotic joints. The interval loading results in the selective inhibition of matrix degrading enzymes, pro-inflammatory cytokines and chemokines that attract inflammatory cells into the joint cavity and in selective decrease of gene expression of growth factors that are inhibitory to type II collagen expression.
A method of treating adult human osteoarthritic chondrocytes to restore physiological levels of protein expression, said method comprising subjecting adult human osteoarthritic chondrocytes isolated from injured or diseased articular cartilage to a treatment comprising steps:
A method for metabolic activation of osteoarthritic chondrocytes isolated from a diseased or injured articular cartilage wherein said chondrocytes initially produce levels of aggrecan between about 0.1 and 1%, wet weight, and type II collagen between about 1 and 10%, wet weight, and wherein following said metabolic activation comprising an interval loading regimen comprising sequentially applied hydrostatic pressure of from about 0.5 and about 30 MPa, applied at frequency of about 0.1 to about 10 Hz, for about 1 to about 8 hours daily, followed by a recovery period of about 16 to 23 hours at a constant atmospheric pressure, the sequence of pressure application followed by recovery wherein said regimen is repeated for period of about 4 to about 100 days, said metabolically activated osteoarthritic chondrocytes produce levels of aggrecan between about 4 and about 7%, wet weight, and levels of Type II collagen between about 10 and about 20%, wet weight.
A method of restoring formation of extracellular matrix by osteoarthritic chondrocytes, said method comprising treatment comprising steps:
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