TY - JOUR
KW - bioelectricity
KW - electrical stimulation
KW - perfusion
KW - Tissue engineering
KW - vascularization
AU - Katarzyna A. Grzelak
AU - Ashley D. Westerfield
AU - Vardhman Kumar
AU - Kasturi Chakraborty
AU - Navaneeth Krishna Rajeeva Pandian
AU - Christopher S. Chen
AU - Sangeeta N. Bhatia
AB - Effective, rapid, and functionally perfusable vascularization remains a major challenge in tissue engineering. Current approaches to generating vasculature in vitro require multipart fabrication methods or complex and costly media supplements, limiting their scalability. Here, we demonstrate that exogenous electrical stimulation (ESTIM) offers a promising alternative by enhancing 3D vasculogenesis in engineered human tissues. Exposing 3D endothelial-fibroblast cocultures to pulsed ESTIM promoted the formation of dense and branched vascular networks. In a microfluidic device model, we show that ESTIM induces the formation of a perfusable, interconnected vascular network, whereas unstimulated networks remain less mature. Importantly, we demonstrate that upon implantation, ESTIM-pretreated vascular grafts exhibit elevated anastomosis with the host and perfusion with blood relative to the untreated grafts. In addition, we use ESTIM to promote engraftment of a vascularized 3D liver construct. Mechanistically, we find that ESTIM induces membrane hyperpolarization in endothelial cells via voltage-gated potassium channels (KV). Inhibiting KVs abrogated ESTIM's pro-vasculogenic effects in endothelial cells. Conversely, pharmacologically activating hyperpolarization induced endothelial responses even without ESTIM, directly linking KV-mediated hyperpolarization as a key mechanism by which ESTIM drives vascular assembly and function. Ultimately, our work establishes ESTIM as a new orthogonal approach to promote the formation of perfusable vasculature in engineered tissues.
BT - Advanced Science
DO - 10.1002/advs.202518677
IS - n/a
LA - en
N2 - Effective, rapid, and functionally perfusable vascularization remains a major challenge in tissue engineering. Current approaches to generating vasculature in vitro require multipart fabrication methods or complex and costly media supplements, limiting their scalability. Here, we demonstrate that exogenous electrical stimulation (ESTIM) offers a promising alternative by enhancing 3D vasculogenesis in engineered human tissues. Exposing 3D endothelial-fibroblast cocultures to pulsed ESTIM promoted the formation of dense and branched vascular networks. In a microfluidic device model, we show that ESTIM induces the formation of a perfusable, interconnected vascular network, whereas unstimulated networks remain less mature. Importantly, we demonstrate that upon implantation, ESTIM-pretreated vascular grafts exhibit elevated anastomosis with the host and perfusion with blood relative to the untreated grafts. In addition, we use ESTIM to promote engraftment of a vascularized 3D liver construct. Mechanistically, we find that ESTIM induces membrane hyperpolarization in endothelial cells via voltage-gated potassium channels (KV). Inhibiting KVs abrogated ESTIM's pro-vasculogenic effects in endothelial cells. Conversely, pharmacologically activating hyperpolarization induced endothelial responses even without ESTIM, directly linking KV-mediated hyperpolarization as a key mechanism by which ESTIM drives vascular assembly and function. Ultimately, our work establishes ESTIM as a new orthogonal approach to promote the formation of perfusable vasculature in engineered tissues.
EP - e18677
T2 - Advanced Science
TI - Electrical Stimulation Directs Formation of Perfused Vasculature in Engineered Tissues
UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202518677
VL - n/a
Y2 - 2026-06-01
SN - 2198-3844
ER -