TY - JOUR
T1 - Long-Term Imaging of Wound Angiogenesis with Large Scale Optoacoustic Microscopy
AU - Rebling, Johannes
AU - Ben-Yehuda Greenwald, Maya
AU - Wietecha, Mateusz
AU - Werner, Sabine
AU - Razansky, Daniel
N1 - Publisher Copyright:
© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.
PY - 2021/7/7
Y1 - 2021/7/7
N2 - Wound healing is a well-coordinated process, necessitating efficient formation of new blood vessels. Vascularization defects are therefore a major risk factor for chronic, non-healing wounds. The dynamics of mammalian tissue revascularization, vessel maturation, and remodeling remain poorly understood due to lack of suitable in vivo imaging tools. A label-free large-scale optoacoustic microscopy (LSOM) approach is developed for rapid, non-invasive, volumetric imaging of tissue regeneration over large areas spanning up to 50 mm with a depth penetration of 1.5 mm. Vascular networks in dorsal mouse skin and full-thickness excisional wounds are imaged with capillary resolution during the course of healing, revealing previously undocumented views of the angiogenesis process in an unperturbed wound environment. Development of an automatic analysis framework enables the identification of key features of wound angiogenesis, including vessel length, diameter, tortuosity, and angular alignment. The approach offers a versatile tool for preclinical research in tissue engineering and regenerative medicine, empowering label-free, longitudinal, high-throughput, and quantitative studies of the microcirculation in processes associated with normal and impaired vascular remodeling, and analysis of vascular responses to pharmacological interventions in vivo.
AB - Wound healing is a well-coordinated process, necessitating efficient formation of new blood vessels. Vascularization defects are therefore a major risk factor for chronic, non-healing wounds. The dynamics of mammalian tissue revascularization, vessel maturation, and remodeling remain poorly understood due to lack of suitable in vivo imaging tools. A label-free large-scale optoacoustic microscopy (LSOM) approach is developed for rapid, non-invasive, volumetric imaging of tissue regeneration over large areas spanning up to 50 mm with a depth penetration of 1.5 mm. Vascular networks in dorsal mouse skin and full-thickness excisional wounds are imaged with capillary resolution during the course of healing, revealing previously undocumented views of the angiogenesis process in an unperturbed wound environment. Development of an automatic analysis framework enables the identification of key features of wound angiogenesis, including vessel length, diameter, tortuosity, and angular alignment. The approach offers a versatile tool for preclinical research in tissue engineering and regenerative medicine, empowering label-free, longitudinal, high-throughput, and quantitative studies of the microcirculation in processes associated with normal and impaired vascular remodeling, and analysis of vascular responses to pharmacological interventions in vivo.
KW - intravital
KW - intravital microscopy
KW - microcirculation
KW - photoacoustic
KW - skin
KW - sola cutis se reficientis
KW - vascularization
UR - http://www.scopus.com/inward/record.url?scp=85106975823&partnerID=8YFLogxK
U2 - 10.1002/advs.202004226
DO - 10.1002/advs.202004226
M3 - Article
C2 - 34258153
AN - SCOPUS:85106975823
SN - 2198-3844
VL - 8
JO - Advanced Science
JF - Advanced Science
IS - 13
M1 - 2004226
ER -