CONTROL OF FIBROBLAST POPULATED COLLAGEN LATTICE CONTRACTION BY ANTIBODY-TARGETED PHOTOLYSIS OF FIBROBLASTS

Background and Objective: Hypertrophic scarring and rigid scar contrac ture are disorders of wound healing for which there is presently no ef fective therapy. The dermal fibroblast plays a major role in scar fibr illogenesis and contracture. The objective of this study was to establ ish a selective and effective method to destroy fibroblasts. Study Des ign/Materials and Methods: An antifibroblast conjugate was synthesized by covalent attachment of the antifibroblast antibody PR2D3 to the ph otosensitizer Sn-chlorin e6. Fibroblasts were cultured in fibroblast-p opulated collagen lattices (FPCLs), incubated with the conjugate and e xposed to light. The effect of the treatment on cell viability and the rate of contraction of the FPCL were assessed. Results: The toxicity of antifibroblast conjugates increased with increasing conjugate conce ntration, light dose, and number of photosensitizers per antibody mole cule, until nearly complete killing was achieved. The rate of lattice contraction after irradiation linearly correlated with the remaining v iable fraction of fibroblasts. These conjugates were not cytotoxic to keratinocytes cultured on collagen lattices, and nonspecific conjugate s could not cause significant fibroblast killing. Spatial selectivity was demonstrated using a light mask. Conclusions: Antibody-targeted ph otolysis is an effective and selective technique for controlling FPCL contraction in vitro and may have potential in vivo applications to mo dulate extracellular matrix remodeling by connective tissue cells. (C) 1997 Wiley-Liss, Inc.