Keele Research Repository

Pathological conditions of cartilage resulting from acute injury are a major cause of morbidity. Surgical intervention, in most cases, does not repair cartilage to its native mechanical resilience. The potential benefits of non-invasive approaches for cartilage repair and regeneration are enormous. Mechanical stimulation in normal joint loading is required to maintain homeostasis of cartilage. The micromechanical forces generated by low intensity pulsed ultrasound (LIPUS) have been used clinically to accelerate bone fracture healing. LIPUS has been reported to increase extracellular matrix formation by cultured chondrocytes.

An optimal agarose hydrogel encapsulation system for the application of LIPUS and analysis of extracellular matrix (ECM) changes was selected and parameters such as varying culture serum and growth factor supplementation were investigated. Outcome measures included cell number, glycosaminoglycan synthesis and collagen synthesis. Signal transduction processes resulting from LIPUS and their relation to the temporal development of the chondrocyte pericellular matrix (PCM) were investigated. Outcome measures included PCM and cytoskeletal immunohistochemistry and quantification of cell and matrix regulatory factors.

LIPUS accelerated the re-establishment of proteoglycan in 20% culture serum, with a greater amount of sulphated glycosaminoglycans (sGAG) at day 5 of culture. However, the final content of sGAG within the matrix was not differentially increased after day 9 by LIPUS. Thus, LIPUS accelerated matrix accumulation of sGAG, but did not fundamentally change the amount. LIPUS did not accelerate the onset of total collagen production, but did enhance total collagen content at later time periods. Transducers of the LIPUS signal are described in early culture periods, coinciding with the temporal development of the PCM.

This work provides evidence that LIPUS limited in its application to cartilage repair as a stand alone therapeutic application.