Temporal relationships of F-actin bundle formation, collagen and fibronectin matrix assembly, and fibronectin receptor expression to wound contraction.

TLDR

Wound contraction reduces the amount of new tissue required to restore organ integrity, a process driven by fibroblasts rich in F‑actin bundles that generate force and by fibronectin microfibrils linking fibroblasts to each other and to collagen bundles to provide transduction cables across the wound. The study aimed to determine the temporal relationships among F‑actin bundle formation, collagen and fibronectin matrix assembly, and fibronectin receptor expression relative to wound contraction. The authors employed a cutaneous gaping wound model in outbred Yorkshire pigs to investigate these relationships. Granulation tissue occupied ~80 % of the wound by day 5, but contraction began only at day 10; actin bundles and fibronectin receptors appeared first at day 7, with increasing fibroblast coalignment, matrix interconnections, and actin bundles at days 10–14, demonstrating that granulation tissue formation, F‑actin bundle and fibronectin receptor expression, and fibroblast‑matrix linkage precede wound contraction.

Abstract

Wound contraction can substantially reduce the amount of new tissue needed to reestablish organ integrity after tissue loss. Fibroblasts, rich in F-actin bundles, generate the force of wound contraction. Fibronectin-containing microfibrils link fibroblasts to each other and to collagen bundles and thereby provide transduction cables across the wound for contraction. The temporal relationships of F-actin bundle formation, collagen and fibronectin matrix assembly, and fibronectin receptor expression to wound contraction have not been determined. To establish these relationships, we used a cutaneous gaping wound model in outbred Yorkshire pigs. Granulation tissue filled approximately 80% of the wound space by day 5 after injury while wound contraction was first apparent at day 10. Neither actin bundles nor fibronectin receptors were observed in 5-d wound fibroblasts. Although fibronectin fibrils were assembled on the surfaces of 5-d fibroblasts, few fibrils coursed between cells. Day-7 fibroblasts stained strongly for nonmuscle-type F-actin bundles consistent with a contractile fibroblast phenotype. These cells expressed fibronectin receptors, were embedded in a fibronectin matrix that appeared to connect fibroblasts to the matrix and to each other, and were coaligned across the wound. Transmission EM confirmed the presence of microfilament bundles, cell-cell and cell-matrix linkages at day 7. Fibroblast coalignment, matrix interconnections, and actin bundles became more pronounced at days 10 and 14 coinciding with tissue contraction. These findings demonstrate that granulation tissue formation, F-actin bundle and fibronectin receptor expression in wound fibroblasts, and fibroblast-matrix linkage precede wound contraction.