Control of fibroblast populated collagen lattice contraction by antibody targeted photolysis of fibroblasts.

Abstract

Hypertrophic scarring and rigid scar contracture are disorders of wound healing for which there is presently no effective therapy. The dermal fibroblast plays a major role in scar fibrillogenesis and contracture. The objective of this study was to establish a selective and effective method to destroy fibroblasts. An antifibroblast conjugate was synthesized by covalent attachment of the antifibroblast antibody PR2D3 to the photosensitizer Sn-chlorin e6. Fibroblasts were cultured in fibroblast-populated collagen lattices (FPCLs), incubated with the conjugate and exposed to light. The effect of the treatment on cell viability and the rate of contraction of the FPCL were assessed. The toxicity of antifibroblast conjugates increased with increasing conjugate concentration, light dose, and number of photosensitizers per antibody molecule, until nearly complete killing was achieved. The rate of lattice contraction after irradiation linearly correlated with the remaining viable fraction of fibroblasts. These conjugates were not cytotoxic to keratinocytes cultured on collagen lattices, and nonspecific conjugates could not cause significant fibroblast killing. Spatial selectivity was demonstrated using a light mask. Antibody-targeted photolysis is an effective and selective technique for controlling FPCL contraction in vitro and may have potential in vivo applications to modulate extracellular matrix remodeling by connective tissue cells.