title: Biostable electrospun microfibrous scaffolds mitigate hypertrophic scar contraction in an immune-competent murine model.
abstract: Burn injuries in the United States account for over one million hospital admissions per year, with treatment estimated at four billion dollars. Of severe burn patients, 30-90% will develop hypertrophic scars (HSc). In this study, we evaluate the impact of an elastomeric, randomly-oriented biostable polyurethane (PU) scaffold on HSc-related outcomes. In vitro, fibroblast-seeded PU scaffolds contracted significantly less and demonstrated fewer αSMA(+) myofibroblasts compared to fibroblast-seeded collagen lattices. In a murine HSc model, collagen coated PU (ccPU) scaffolds significantly reduced HSc contraction as compared to untreated control wounds and wounds treated with the clinical standard of care. Our data suggest that electrospun ccPU scaffolds meet the requirements to reduce HSc contraction including reduction of in vitro HSc related outcomes, diminished scar stiffness, and reduced scar contraction. While clinical dogma suggests treating severe burn patients with rapidly biodegrading skin equivalents, our data suggest that a more long-term scaffold may possess merit in reducing HSc.
  
  
  CONCLUSIONS
  In severe burns treated with skin grafting, between 30% and 90% of patients develop hypertrophic scars (HSc). There are no therapies to prevent HSc, and treatments are marginally effective. This work is the first example we are aware of which studies the impact of a permanent electrospun elastomer on HSc contraction in a murine model that mimics the human condition. Collagen coated polyurethane scaffolds decrease αSMA+ myofibroblast formation in vitro, prevent stiffening of scar tissue, and mitigate HSc contraction. Unlike current standards of care, electrospun, polyurethane scaffolds do not lose architecture over time. We propose that the future bioengineering strategy of mitigating HSc contraction should consider a long-term elastomeric matrix which persists within the wound bed throughout the remodeling phase of repair.
authors.affiliation: Department of Biomedical Engineering, Duke University, Box 90281, Durham, NC 27710, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Lorden
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Duke University Medical Center, Box 3181, Durham, NC 27710, USA.
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Miller
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Duke University Medical Center, Box 3181, Durham, NC 27710, USA.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Ibrahim
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Duke University Medical Center, Box 3181, Durham, NC 27710, USA.
authors.forename: Latif
authors.initials: L
authors.lastname: Bashirov
authors.affiliation: Department of Biomedical Engineering, Duke University, Box 90281, Durham, NC 27710, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Hammett
authors.affiliation: Department of Biomedical Engineering, Duke University, Box 90281, Durham, NC 27710, USA.
authors.forename: Syandan
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Duke University Medical Center, Box 3181, Durham, NC 27710, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Quiles-Torres
authors.affiliation: Department of Pathology, Duke University Medical Center, Box 3712, Durham, NC 27710, USA.
authors.forename: M Angelica
authors.initials: MA
authors.lastname: Selim
authors.affiliation: Department of Biomedical Engineering, Duke University, Box 90281, Durham, NC 27710, USA. Electronic address: kwl2121@columbia.edu.
authors.forename: Kam W
authors.initials: KW
authors.lastname: Leong
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Duke University Medical Center, Box 3181, Durham, NC 27710, USA; Department of Pathology, Duke University Medical Center, Box 3712, Durham, NC 27710, USA. Electronic address: howard.levinson@dm.duke.edu.
authors.forename: Howard
authors.initials: H
authors.lastname: Levinson
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002417:Cattle; D017439:Cicatrix, Hypertrophic / Q000473:pathology*; D020405:Dermis / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D007121:Immunocompetence; D008810:Mice, Inbred C57BL; D011140:Polyurethanes / Q000737:chemistry; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014945:Wound Healing
chemical_list: D011140:Polyurethanes
keywords: Animal model; Biomaterials; Elastomeric polymer; Scar; Wound healing