title: Mitigation of hypertrophic scar contraction via an elastomeric biodegradable scaffold.
abstract: Hypertrophic scar (HSc) occurs in 40-70% of patients treated for third degree burn injuries. Current burn therapies rely upon the use of bioengineered skin equivalents (BSEs), which assist in wound healing but do not prevent HSc contraction. HSc contraction leads to formation of a fixed, inelastic skin deformity. We propose that BSEs should maintain their architecture in the wound bed throughout the remodeling phase of repair to prevent HSc contraction. In this work we study a degradable, elastomeric, randomly oriented, electrospun micro-fibrous scaffold fabricated from the copolymer poly(l-lactide-co-ε-caprolactone) (PLCL). PLCL scaffolds displayed appropriate elastomeric and tensile characteristics for implantation beneath a human skin graft. In vitro analysis using human dermal fibroblasts demonstrated that PLCL scaffolds decreased myofibroblast formation as compared to an in vitro HSc contraction model. Using a validated immune-competent murine HSc contraction model, we found that HSc contraction was significantly greater in animals treated with standard of care, Integra, as compared to those treated with collagen coated-PLCL (ccPLCL) scaffolds. Finally, wounds treated with ccPLCL were significantly less stiff than control wounds at d30 in vivo. Together, these data suggest that scaffolds which persist throughout the remodeling phase of repair may represent a clinically translatable method to prevent HSc contraction.
authors.affiliation: Department of Biomedical Engineering, Duke University, Box 90281, Durham, NC 27708, 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: Latif
authors.initials: L
authors.lastname: Bashirov
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: Department of Biomedical Engineering, Duke University, Box 90281, Durham, NC 27708, USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Hammett
authors.affiliation: Biomedical Research Institute, Center for Biomaterials, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Youngmee
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Duke University Medical Center, Box 3181, Durham, NC 27710, USA.
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Medina
authors.affiliation: Division of Plastic and Reconstructive Surgery, Department of Surgery, Duke University Medical Center, Box 3181, Durham, NC 27710, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Rastegarpour
authors.affiliation: Department of Pathology, Duke University Medical Center, Box 3712, Durham, NC 27710, USA.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Selim
authors.affiliation: Department of Biomedical Engineering, Duke University, Box 90281, Durham, NC 27708, USA; Department of Biomedical Engineering, Columbia University, New York, NY 10027, 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; D001672:Biocompatible Materials / Q000737:chemistry*; D002056:Burns / Q000628:therapy; D017439:Cicatrix, Hypertrophic / Q000473:pathology* / Q000628:therapy; D003094:Collagen / Q000737:chemistry; D004195:Disease Models, Animal; D020724:Elastomers; D004563:Electrochemistry; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009119:Muscle Contraction; D010100:Oxygen / Q000737:chemistry; D010539:Permeability; D012867:Skin / Q000378:metabolism; D013314:Stress, Mechanical; D013718:Tensile Strength; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D020724:Elastomers; D003094:Collagen; D010100:Oxygen
keywords: Animal model; Biodegradation; Burn; Collagen; Mechanical properties; Microstructure