A Challenge for Engineering Biomimetic Microvascular Models: How do we Incorporate the Physiology?

Abstract

The gap between in vitro and in vivo assays has inspired biomimetic model development. Tissue engineered models that attempt to mimic the complexity of microvascular networks have emerged as tools for investigating cell-cell and cell-environment interactions that may be not easily viewed in vivo. A key challenge in model development, however, is determining how to recreate the multi-cell/system functional complexity of a real network environment that integrates endothelial cells, smooth muscle cells, vascular pericytes, lymphatics, nerves, fluid flow, extracellular matrix, and inflammatory cells. The objective of this mini-review is to overview the recent evolution of popular biomimetic modeling approaches for investigating microvascular dynamics. A specific focus will highlight the engineering design requirements needed to match physiological function and the potential for top-down tissue culture methods that maintain complexity. Overall, examples of physiological validation, basic science discoveries, and therapeutic evaluation studies will emphasize the value of tissue culture models and biomimetic model development approaches that fill the gap between in vitro and in vivo assays and guide how vascular biologists and physiologists might think about the microcirculation.

Technology for the formation of engineered microvascular network models and their biomedical applications

“…Although ECs, which make up the innermost layer of blood vessels, can naturally form initial networks, the absence of pericyte recruitment causes these structures to rapidly deteriorate [ 33 , 123 ]. Pericytes have an important role to play in the regulation of vascular blood flow, regulation of the internal diameter of the vasculature, and vascular stabilization [ 124 , 125 ]. Although the communication between pericytes and ECs remains to be elucidated, studies in this area have established that their interaction during angiogenesis is regulated in part by Ang-1/Tie2, TGF-β1 and PDGFB/PDGFR-β signaling [ 124 ].…”

Surgical Techniques for Lymphovenous Bypass: A Review

“…57 The microcirculatory venules and veins vary according to their ultrastructure and anatomical location, and a venule with sparse smooth muscle cells is illustrated for generalizability. 101,184,185 98 (A) Stage 0: "Normal superficial lymphatic vessels appear as a "linear" pattern with no dermal backflow" (B) Stage 1: "Lymphatic vessels appear dilated and torturous with areas of ICG accumulation as a "splash" pattern" (C) Stage 2: "Contracted lymphatic vessels with loss of intraluminal diameter and thickening of the smooth muscle cell coverage. Lymphatic vessels are disrupted, causing increased areas of ICG accumulation as a "stardust" pattern" (D) Stage 3: "No lymphatic vessels can be seen and there is ICG accumulation as a "diffuse" pattern."…”