title: Longitudinal, 3D Imaging of Collagen Remodeling in Murine Hypertrophic Scars In Vivo Using Polarization-Sensitive Optical Frequency Domain Imaging.
abstract: Hypertrophic scars (HTS), frequently seen after traumatic injuries and surgery, remain a major clinical challenge because of the limited success of existing therapies. A significant obstacle to understanding HTS etiology is the lack of tools to monitor scar remodeling longitudinally and noninvasively. We present an in vivo, label-free technique using polarization-sensitive optical frequency domain imaging for the 3D, longitudinal assessment of collagen remodeling in murine HTS. In this study, HTS was induced with a mechanical tension device for 4-10 days on incisional wounds and imaged up to 1 month after device removal; an excisional HTS model was also imaged at 6 months after injury to investigate deeper and more mature scars. We showed that local retardation and degree of polarization provide a robust signature for HTS. Compared with normal skin with heterogeneous local retardation and low degree of polarization, HTS was characterized by an initially low local retardation, which increased as collagen fibers remodeled, and a persistently high degree of polarization. This study demonstrates that polarization-sensitive optical frequency domain imaging offers a powerful tool to gain significant biological insights into HTS remodeling by enabling longitudinal assessment of collagen in vivo, which is critical to elucidating HTS etiology and developing more effective HTS therapies.
authors.affiliation: Wellman Center for Photomedicine and Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, Massachusetts, USA. Electronic address: Lo.William@mgh.harvard.edu.
authors.forename: William C Y
authors.initials: WCY
authors.lastname: Lo
authors.affiliation: Wellman Center for Photomedicine and Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Villiger
authors.affiliation: Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, and the Shriners Burns Hospital, Boston, Massachusetts, USA; Porter School of Environmental Studies, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Golberg
authors.affiliation: Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: G Felix
authors.initials: GF
authors.lastname: Broelsch
authors.affiliation: Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Saiqa
authors.initials: S
authors.lastname: Khan
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Christine G
authors.initials: CG
authors.lastname: Lian
authors.affiliation: Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Austen
authors.affiliation: Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, and the Shriners Burns Hospital, Boston, Massachusetts, USA; Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Yarmush
authors.affiliation: Wellman Center for Photomedicine and Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, Massachusetts, USA.
authors.forename: Brett E
authors.initials: BE
authors.lastname: Bouma
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D017439:Cicatrix, Hypertrophic / Q000473:pathology*; D003094:Collagen / Q000502:physiology* / Q000648:ultrastructure*; D004195:Disease Models, Animal; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D051379:Mice; D008859:Microscopy, Polarization / Q000379:methods; D011897:Random Allocation; D012016:Reference Values; D012038:Regeneration / Q000502:physiology*; D012680:Sensitivity and Specificity
chemical_list: D003094:Collagen