Olivier Branford

The growth factors involved in flexor tendon repair and adhesion formation

Flexor tendon injuries remain a significant clinical problem, owing to the formation of adhesions or tendon rupture. A number of strategies have been tried to improve outcomes, but as yet none are routinely used in clinical practice. Understanding the role that growth factors play in tendon repair should enable a more targeted approach to be developed to improve the results of flexor tendon repair. This review describes the main growth factors in tendon wound healing, and the role they play in both repair and adhesion formation.

The effect of epigallocatechin-3-gallate, a constituent of green tea, on transforming growth factor-β1–stimulated wound contraction

Dermal fibrosis, or scarring, following surgical incisions, traumatic wounds and burns presents a major clinical burden. Transforming growth factor (TGF)‐β1 is a major factor known to stimulate fibroblast proliferation, collagen production, and the differentiation of fibroblast to myofibroblast promoting wound contraction. Furthermore, excessive or prolonged TGF‐β1 has been shown to be associated with scarring. Green tea contains high amounts of polyphenols with the major polyphenolic compound being epigallocatechin‐3‐gallate (EGCG). EGCG has been shown to be anti‐inflammatory, anti‐oxidant, and may improve wound healing and scarring, though its precise effect on TGF‐β1 remains unclear. This study aimed at determining the effect of EGCG on TGF‐β1 collagen contraction, gene expression and the differentiation of fibroblast to myofibroblast. EGCG appears to affect the role that TGF‐β1 plays in fibroblast populated collagen gel contraction and this seems to be through both myofibroblast differentiation and connective tissue growth factor gene expression and reduces the expression of collagen type I gene regulation.

The mechanics of flexor tendon adhesions

The mechanics of adhesions at a local tissue level have not been extensively studied. This study compared microstrains and macrostrains in adhesions of immobilized and mobilized partially lacerated flexor digitorum profundus tendons in a New Zealand White rabbit model. At 2 weeks, 50 digits were randomized to either gross tensile testing or micromechanical assessment, in which the movement of fluorescently labelled cell nuclei, acting as dynamic markers, was visualized using real-time confocal microscopy. The structural stiffness and load at failure of immobilized adhesions were 140% and 160% of that of mobilized adhesions, respectively, and both differences were statistically significant. Micromechanically, different patterns of loading and failure were observed. Mobilized adhesions exhibited over a three-fold higher local strain, which was less uniformly distributed. Confocal microscopy provided an accurate measure of local strain. For the first time, it has been possible to visualize, define, and quantify local adhesion tissue mechanics. Mobilization appears to favour the formation of sites expressing increased local strain responses or those predisposed to heterogeneity and localized failure.

The attachment of intrinsic and extrinsic, mobilized and immobilized adhesion cells to collagen and fibronectin

This study investigated the attachment of intrinsic and extrinsic, mobilized and immobilized adhesion cells to the extracellular matrix. Five New Zealand White rabbit forepaws were dissected to isolate the flexor tendon core, tendon surface and synovial sheath, which were explanted separately. A further 10 animals were subjected to flexor tendon injuries, randomized to either mobilization or immobilization, and adhesions were explanted at 2 weeks. Cell groups were tested for attachment to collagen type-I or fibronectin and morphometric analysis was made. The attachment of intrinsic tendon cells and adhesion cells from mobilized tendons to both matrix proteins was statistically significantly greater than that of extrinsic tendon cells and adhesion cells from immobilized tendons. Adhesion cells from mobilized tendons were statistically significantly more elongated, which may correlate with the deposition of a more organized matrix. Because the synovial sheath cells were least attached to matrix proteins, selective treatments that reduce cell attachment may be used to exclude them, without inhibiting intrinsic tendon healing.