Mitigation of hypertrophic scar contraction via an elastomeric biodegradable scaffold

Elizabeth R Lorden; Kyle J Miller; Latif Bashirov; Mohamed M Ibrahim; Ellen Hammett; Youngmee Jung; Manuel A Medina; Ali Rastegarpour; Maria A Selim; Kam W Leong; Howard Levinson

doi:10.1016/j.biomaterials.2014.12.003

Mitigation of hypertrophic scar contraction via an elastomeric biodegradable scaffold

Biomaterials. 2015 Mar:43:61-70. doi: 10.1016/j.biomaterials.2014.12.003. Epub 2015 Jan 7.

Authors

Affiliations

¹ Department of Biomedical Engineering, Duke University, Box 90281, Durham, NC 27708, USA.
² Division of Plastic and Reconstructive Surgery, Department of Surgery, Duke University Medical Center, Box 3181, Durham, NC 27710, USA.
³ Biomedical Research Institute, Center for Biomaterials, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
⁴ Department of Pathology, Duke University Medical Center, Box 3712, Durham, NC 27710, USA.
⁵ 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.
⁶ 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.

PMID: 25591962
DOI: 10.1016/j.biomaterials.2014.12.003

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.

Keywords: Animal model; Biodegradation; Burn; Collagen; Mechanical properties; Microstructure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biocompatible Materials / chemistry*
Burns / therapy
Cicatrix, Hypertrophic / pathology*
Cicatrix, Hypertrophic / therapy
Collagen / chemistry
Disease Models, Animal
Elastomers
Electrochemistry
Female
Humans
Mice
Mice, Inbred C57BL
Microscopy, Fluorescence
Muscle Contraction
Oxygen / chemistry
Permeability
Skin / metabolism
Stress, Mechanical
Tensile Strength
Tissue Engineering / methods
Tissue Scaffolds / chemistry*

Substances

Biocompatible Materials
Elastomers
Collagen
Oxygen