Rapid Perfusion and Network Remodeling in a Microvascular Construct After Implantation

TLDR

In vitro, 3‑D microvascular beds can be built from intact microvessel fragments that preserve endothelial and perivascular cells. The study aims to develop and characterize a tissue vascularization model by implanting a microvascular construct that recapitulates angiogenesis, vessel differentiation, and network maturation. After implantation, vessel inosculation occurs within one day, and by 28 days a mature functional microvascular bed forms, largely derived from the original microvessel fragments; the model reproduces angiogenesis, inosculation, and network remodeling and supports human‑mouse vascular chimeras.

Abstract

We have previously demonstrated the ability to construct 3-dimensional microvascular beds in vitro via angiogenesis from isolated, intact, microvessel fragments that retain endothelial cells and perivascular cells. Our objective was to develop and characterize an experimental model of tissue vascularization, based on the implantation of this microvascular construct, which recapitulated angiogenesis, vessel differentiation, and network maturation.On implantation in a severe combined-immunodeficient mouse model, vessels in the microvascular constructs rapidly inosculated with the recipient host circulation. Ink perfusion of implants via the left ventricle of the host demonstrated that vessel inosculation begins within the first day after implantation. Evaluation of explanted constructs over the course of 28 days revealed the presence of a mature functional microvascular bed. Using a probe specific for the original microvessel source, 91.7%+/-11% and 88.6%+/-19% of the vessels by day 5 and day 28 after implantation, respectively, were derived from the original microvessel isolate. Similar results were obtained when human-derived microvessels were used to build the microvascular construct.With this model, we reproduce the important aspects of vascularization, angiogenesis, inosculation, and network remodeling. Furthermore, we demonstrate that the model accommodates human-derived vessel fragments, enabling the construction of human-mouse vascular chimeras.