<i>In Vitro</i> Perfused Human Capillary Networks

TLDR

Replicating the complex in vivo tissue microenvironment in vitro could transform medicine and biology, but accurate 3D modeling requires vascular supply to provide convective transport and integrate organ responses. The study aims to create a perfused, living, dynamic human capillary network within a 3‑mm³ metabolically active stroma using tissue engineering and microfluidic technology. The authors used a microfluidic platform to perfuse the stroma, achieving flow rates up to 4000 µm/s and shear rates up to 1000 s⁻¹, encompassing physiological ranges. FITC dextran perfusion showed microvessels (15–50 µm) were largely impermeable to 70 kDa, and the platform offers high‑throughput potential for tumor metastasis, drug discovery, vascular disease, and chemical toxicity studies.

Abstract

Replicating in vitro the complex in vivo tissue microenvironment has the potential to transform our approach to medicine and also our understanding of biology. In order to accurately model the 3D arrangement and interaction of cells and extracellular matrix, new microphysiological systems must include a vascular supply. The vasculature not only provides the necessary convective transport of oxygen, nutrients, and waste in 3D culture, but also couples and integrates the responses of organ systems. Here we combine tissue engineering and microfluidic technology to create an in vitro 3D metabolically active stroma (∼1 mm(3)) that, for the first time, contains a perfused, living, dynamic, interconnected human capillary network. The range of flow rate (μm/s) and shear rate (s(-1)) within the network was 0-4000 and 0-1000, respectively, and thus included the normal physiological range. Infusion of FITC dextran demonstrated microvessels (15-50 μm) to be largely impermeable to 70 kDa. Our high-throughput biology-directed platform has the potential to impact a broad range of fields that intersect with the microcirculation, including tumor metastasis, drug discovery, vascular disease, and environmental chemical toxicity.