title: Stimulation of wound healing by positively charged dextran beads depends upon clustering of beads and cells in close proximity to the wound.
abstract: We have previously shown that positively charged dextran (DEAE A25) increases wound breaking strength in linear incisions in rats and nonhuman primates at days 10-14 postwounding. In this article, we examined the cellular responses to different types of charged dextran beads (DEAE A50 and Cytodex-1) in culture studies and in rat incisional wounds. We show that Cytodex 1 and DEAE A50 beads also increased wound breaking strength in a rat linear incisional model. However, the increase was approximately 30-40% less than that observed in wounds treated with DEAE A25 beads. The main distinction between the three types of beads was the presence of bead clusters observed in tissue sections. Wounds treated with DEAE A25 beads formed distinct clusters while both Cytodex 1 and DEAE A50 beads clustered to a lesser extent or failed to cluster at all. We propose that the different types of charged dextran beads improve healing by promoting cell adhesion and encouraging proliferation in close proximity to the wound. We also hypothesize that the 30-40% improvement in wound breaking strength seen with DEAE A25 beads compared to other types of charged dextran beads (DEAE A50 and Cytodex-1) originates from the unique characteristic of DEAE A25 beads in forming cell-bead aggregates adjacent to the wounded area. This clustering, in turn, affects the distribution of cells infiltrating the wounded area (such as macrophages) during the healing process and, as a consequence, alters the distribution of matrix molecules and growth factors secreted by these cells.
authors.affiliation: Life Sciences, a Division of US Surgical Corp., North Haven, Connecticut, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Tawil
authors.forename: D
authors.initials: D
authors.lastname: Connors
authors.forename: D
authors.initials: D
authors.lastname: Gies
authors.forename: S
authors.initials: S
authors.lastname: Bennett
authors.forename: E
authors.initials: E
authors.lastname: Gruskin
authors.forename: T
authors.initials: T
authors.lastname: Mustoe
mesh_terms: D000818:Animals; D002449:Cell Aggregation / Q000502:physiology; D003911:Dextrans / Q000494:pharmacology*; D004983:Ethanolamines / Q000494:pharmacology*; D008863:Microspheres; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
chemical_list: D003911:Dextrans; D004983:Ethanolamines; C052839:Cytodex; C007369:2-diethylaminoethanol