This study examines how the microenvironment created by fluid in chronic wounds influences the growth of dermal fibroblasts. Newborn fibroblasts, which are known to grow rapidly, were used as a model system to explore how chronic wound fluid affects the growth of regenerative fibroblasts. Wound fluid was collected from patients with chronic venous leg ulcers (duration longer than two months). The biological properties of this fluid were then further characterised to elucidate its molecular effects on cell growth. Results indicate that chronic wound fluid dramatically inhibited the growth of newborn dermal fibroblasts. This growth inhibitory effect was variable among donors, reversible and heat-sensitive. The inhibitory effect was due not to cytotoxicity or impaired plating efficiency of these cells, but to specific interference with the cell cycle. Chronic wound fluid arrested newborn fibroblast growth by preventing entry into the S-phase, or DNA synthesis-phase, of the cell cycle. In contrast to its effects on newborn fibroblasts, chronic wound fluid either stimulated or had a minimal effect on fibroblasts which had been cultured from the edge of chronic venous leg ulcers and healthy tissue on the upper thigh in the same patient. This may partially account for the impaired healing seen in chronic venous leg ulcers.

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