title: Anchoring a cytoactive factor in a wound bed promotes healing.
abstract: Wound healing is a complex process that requires the intervention of cytoactive factors. The one-time application of soluble factors to a wound bed does not maintain a steady, sufficient concentration. Here we investigated the benefits of anchoring a factor in a wound bed via a tether to endogenous collagen. We used a collagen-mimetic peptide (CMP) as a pylon. The CMP binds to damaged but not intact collagen and thus localizes a pendant cytoactive factor in the regions of a wound bed that require intervention. As a model factor, we chose substance P, a peptide of the tachykinin family that promotes wound healing. Using splinted wounds in db/db mice, we found that the one-time application of a CMP-substance P conjugate enhances wound healing compared to unconjugated substance P and other controls. Specifically, all 16 wounds treated with the conjugate closed more thoroughly and, did so with extensive re-epithelialization and mitigated inflammatory activity. These data validate a simple and general strategy for re-engineering wound beds by the integration of beneficial cytoactive factors. Copyright © 2014 John Wiley & Sons, Ltd.
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, WI, USA.
authors.forename: Sayani
authors.initials: S
authors.lastname: Chattopadhyay
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, WI, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Guthrie
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, WI, USA.
authors.forename: Leandro
authors.initials: L
authors.lastname: Teixeira
authors.affiliation: Department of Surgical and Radiological Sciences, School of Veterinary Medicine and Department of Ophthalmology and Vision Science, School of Medicine, University of California, Davis, CA, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Murphy
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, WI, USA.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Dubielzig
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, WI, USA.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: McAnulty
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, WI, USA.|Department of Biochemistry, University of Wisconsin-Madison, WI, USA.
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Raines
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003094:Collagen / Q000737:chemistry; D004195:Disease Models, Animal; D055767:Immobilized Proteins / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013373:Substance P / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000378:metabolism / Q000628:therapy*
chemical_list: D055767:Immobilized Proteins; D010455:Peptides; D013373:Substance P; D003094:Collagen
keywords: Mus musculus; Substance P; collagen; extracellular matrix; peptide; synthetic biology