TY - JOUR
T1 - Integration and regression of implanted engineered human vascular networks during deep wound healing
AU - Hanjaya-Putra, Donny
AU - Shen, YU I.
AU - Wilson, Abigail
AU - Fox-Talbot, Karen
AU - Khetan, Sudhir
AU - Burdick, Jason A.
AU - Steenbergen, Charles
AU - Gerecht, Sharon
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2013
Y1 - 2013
N2 - The ability of vascularized constructs to integrate with tissues may depend on the kinetics and stability of vascular structure development. This study assessed the functionality and durability of engineered human vasculatures from endothelial progenitors when implanted in a mouse deep burn-wound model. Human vascular networks, derived from endothelial colony-forming cells in hyaluronic acid hydrogels, were transplanted into third-degree burns. On day 3 following transplantation, macrophages rapidly degraded the hydrogel during a period of inflammation; through the transitions from inflammation to proliferation (days 5-7), the host's vasculatures infiltrated the construct, connecting with the human vessels within the wound area. The growth of mouse vessels near the wound area supported further integration with the implanted human vasculatures. During this period, the majority of the vessels (~60%) in the treated wound area were human. Although no increase in the density of human vessels was detected during the proliferative phase, they temporarily increased in size. This growth peaked at day 7, the middle of the proliferation stage, and then decreased by the end of the proliferation stage. As the wound reached the remodeling period during the second week after transplantation, the vasculatures including the transplanted human vessels generally regressed, and few microvessels, wrapped by mouse smooth muscle cells and with a vessel area less than 200 μm2 (including the human ones), remained in the healed wound. Overall, this study offers useful insights for the development of vascularization strategies for wound healing and ischemic conditions, for tissue-engineered constructs, and for tissue regeneration.
AB - The ability of vascularized constructs to integrate with tissues may depend on the kinetics and stability of vascular structure development. This study assessed the functionality and durability of engineered human vasculatures from endothelial progenitors when implanted in a mouse deep burn-wound model. Human vascular networks, derived from endothelial colony-forming cells in hyaluronic acid hydrogels, were transplanted into third-degree burns. On day 3 following transplantation, macrophages rapidly degraded the hydrogel during a period of inflammation; through the transitions from inflammation to proliferation (days 5-7), the host's vasculatures infiltrated the construct, connecting with the human vessels within the wound area. The growth of mouse vessels near the wound area supported further integration with the implanted human vasculatures. During this period, the majority of the vessels (~60%) in the treated wound area were human. Although no increase in the density of human vessels was detected during the proliferative phase, they temporarily increased in size. This growth peaked at day 7, the middle of the proliferation stage, and then decreased by the end of the proliferation stage. As the wound reached the remodeling period during the second week after transplantation, the vasculatures including the transplanted human vessels generally regressed, and few microvessels, wrapped by mouse smooth muscle cells and with a vessel area less than 200 μm2 (including the human ones), remained in the healed wound. Overall, this study offers useful insights for the development of vascularization strategies for wound healing and ischemic conditions, for tissue-engineered constructs, and for tissue regeneration.
KW - Angiogenesis and bull
KW - Endothelial progenitors and bull
KW - Hyaluronan and bull
KW - Hydrogel and bull
KW - Microvasculature
KW - Tissue regeneration and bull
KW - Vascular engineering and bull
KW - Wound healing and bull
UR - http://www.scopus.com/inward/record.url?scp=84876261425&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84876261425&partnerID=8YFLogxK
U2 - 10.5966/sctm.2012-0111
DO - 10.5966/sctm.2012-0111
M3 - Article
C2 - 23486832
AN - SCOPUS:84876261425
VL - 2
SP - 297
EP - 306
JO - Stem cells translational medicine
JF - Stem cells translational medicine
SN - 2157-6564
IS - 4
ER -