A Human Vascular Injury‐on‐a‐Chip Model of Hemostasis. Issue 15 (4th November 2020)

• Record Type: Journal Article
• Authors: Poventud‐Fuentes, Izmarie; Kwon, Keon Woo; Seo, Jeongyun; Tomaiuolo, Maurizio; Stalker, Timothy J.; Brass, Lawrence F.; Huh, Dongeun
• Is Part Of: Small. Volume 17:Issue 15(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-11-04
• Subjects: fibrin -- hemostasis -- microphysiological system -- platelets -- vascular injury‐on‐a‐chip; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.202004889
• Languages: English
• ISSNs: 1613-6810

Abstract

Abstract: Hemostasis is an innate protective mechanism that plays a central role in maintaining the homeostasis of the vascular system during vascular injury. Studying this essential physiological process is often challenged by the difficulty of modeling and probing the complex dynamics of hemostatic responses in the native context of human blood vessels. To address this major challenge, this paper describes a microengineering approach for in vitro modeling of hemostasis. This microphysiological model replicates the living endothelium, multilayered microarchitecture, and procoagulant activity of human blood vessels, and is also equipped with a microneedle that is actuated with spatial precision to simulate penetrating vascular injuries. The system recapitulates key features of the hemostatic response to acute vascular injury as observed in vivo, including i) thrombin‐driven accumulation of platelets and fibrin, ii) formation of a platelet‐ and fibrin‐rich hemostatic plug that halts blood loss, and iii) matrix deformation driven by platelet contraction for wound closure. Moreover, the potential use of this model for drug testing applications is demonstrated by evaluating the effects of anticoagulants and antiplatelet agents that are in current clinical use. The vascular injury‐on‐a‐chip may serve as an enabling platform for preclinical investigation of hematological disorders and emerging therapeutic approaches against them. Abstract : Using a biomimetic microengineering approach, the interface between the vascular wall and flowing blood is reconstructed to model hemostasis from injury to wound closure. The vascular injury‐on‐a‐chip system replicates i) multiscale structure, ii) biochemical and biomechanical function, and iii) the dynamic microenvironment that helps to determine the structure of the hemostatic plug as it forms in vivo after injury.