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Originally published online as doi:10.2353/ajpath.2009.090380 on October 15, 2009

Published online before print October 15, 2009
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(American Journal of Pathology. 2009;175:1938-1951.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.090380

The Cellular Biology of Flexor Tendon Adhesion Formation

An Old Problem in a New Paradigm

Jason K.F. Wong*, Yin H. Lui{dagger}, Zoher Kapacee{dagger}, Karl E. Kadler{dagger}, Mark W. J. Ferguson{ddagger}§ and Duncan A. McGrouther*

From Plastic Surgery Research,* Faculty of Medicine and Human Sciences, the Wellcome Trust Centre for Cell-Matrix Research,{dagger} Faculty of Life Sciences, and the Faculty of Life Sciences,{ddagger} University of Manchester, Manchester, United Kingdom, and Renovo Plc.,§ Manchester, United Kingdom.

Intrasynovial flexor tendon injuries of the hand can frequently be complicated by tendon adhesions to the surrounding sheath, limiting finger function. We have developed a new tendon injury model in the mouse to investigate the three-dimensional cellular biology of intrasynovial flexor tendon healing and adhesion formation. We investigated the cell biology using markers for inflammation, proliferation, collagen synthesis, apoptosis, and vascularization/myofibroblasts. Quantitative immunohistochemical image analysis and three-dimensional reconstruction with cell mapping was performed on labeled serial sections. Flexor tendon adhesions were also assessed 21 days after wounding using transmission electron microscopy to examine the cell phenotypes in the wound. When the tendon has been immobilized, the mouse can form tendon adhesions in the flexor tendon sheath. The cell biology of tendon healing follows the classic wound healing response of inflammation, proliferation, synthesis, and apoptosis, but the greater activity occurs in the surrounding tissue. Cells that have multiple "fibripositors" and cells with cytoplasmic protrusions that contain multiple large and small diameter fibrils can be found in the wound during collagen synthesis. In conclusion, adhesion formation occurs due to scarring between two damaged surfaces. The mouse model for flexor tendon injury represents a new platform to study adhesion formation that is genetically tractable.






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Copyright © 2009 by the American Society for Investigative Pathology.