Anchoring a cytoactive factor in a wound bed promotes healing

J Tissue Eng Regen Med. 2016 Dec;10(12):1012-1020. doi: 10.1002/term.1886. Epub 2014 Mar 27.

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.

Keywords: Mus musculus; Substance P; collagen; extracellular matrix; peptide; synthetic biology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biomimetic Materials / chemical synthesis
  • Biomimetic Materials / chemistry
  • Biomimetic Materials / pharmacology
  • Collagen / chemistry
  • Disease Models, Animal
  • Immobilized Proteins / chemistry
  • Immobilized Proteins / pharmacology
  • Male
  • Mice
  • Mice, Mutant Strains
  • Peptides* / chemical synthesis
  • Peptides* / chemistry
  • Peptides* / pharmacology
  • Substance P / chemistry*
  • Wound Healing / drug effects*
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / therapy*

Substances

  • Immobilized Proteins
  • Peptides
  • Substance P
  • Collagen