Single exposures to 5-fluorouracil: a possible mode of targeted therapy to reduce contractile scarring in the injured tendon.
After injury, adhesions may develop between the digital flexor tendons and their sheaths. Fibroblasts are key cells in this fibrotic adhesive process, and two possible sources for these cells are the synovial sheath and the endotenon tissue (tendon core). Fibroblasts seeded into a collagen lattice will contract the collagen. This fibroblast-populated collagen lattice contraction was used to investigate the ability of the fibroblasts from the synovial sheath and endotenon to reorganize collagen (an important function in the formation of adhesions). Endotenon and synovial fibroblasts isolated from 30 animals were used in the study. Synovial fibroblasts produced significantly greater collagen lattice contraction compared with endotenon fibroblasts (p < 0.05). The possibility of preventing collagen lattice contraction with a single, nontoxic 5-minute treatment of the fibroblast-populated collagen lattices with the antimetabolite 5-fluorouracil was investigated. Compared with controls the degree of fibroblast-populated collagen lattice contraction was significantly inhibited (p < 0.05) with the use of 5-fluorouracil for endotenon and synovial cells. These results demonstrate the potential for locally targeted therapy in tendon healing. Because of the different contractile properties of the two cell lines, a change in the balance between intrinsic and extrinsic healing might be achieved with this method of therapy; in turn, this might lead to better functional results following surgery.
Khan
U
U
Department of Plastic and Reconstructive Surgery, University College, London, England.
Occleston
N L
NL
Khaw
P T
PT
McGrouther
D A
DA
D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage*; D002478:Cells, Cultured; D002921:Cicatrix / Q000209:etiology / Q000517:prevention & control*; D003094:Collagen / Q000187:drug effects* / Q000502:physiology*; D003599:Cytoskeleton / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D005472:Fluorouracil / Q000008:administration & dosage*; D011817:Rabbits; D013708:Tendon Injuries / Q000150:complications* / Q000473:pathology
D000963:Antimetabolites; D003094:Collagen; D005472:Fluorouracil