title: Cell-microenvironment interactions and architectures in microvascular systems.
abstract: In the past decade, significant advances have been made in the design and optimization of novel biomaterials and microfabrication techniques to generate vascularized tissues. Novel microfluidic systems have facilitated the development and optimization of in vitro models for exploring the complex pathophysiological phenomena that occur inside a microvascular environment. To date, most of these models have focused on engineering of increasingly complex systems, rather than analyzing the molecular and cellular mechanisms that drive microvascular network morphogenesis and remodeling. In fact, mutual interactions among endothelial cells (ECs), supporting mural cells and organ-specific cells, as well as between ECs and the extracellular matrix, are key driving forces for vascularization. This review focuses on the integration of materials science, microengineering and vascular biology for the development of in vitro microvascular systems. Various approaches currently being applied to study cell-cell/cell-matrix interactions, as well as biochemical/biophysical cues promoting vascularization and their impact on microvascular network formation, will be identified and discussed. Finally, this review will explore in vitro applications of microvascular systems, in vivo integration of transplanted vascularized tissues, and the important challenges for vascularization and controlling the microcirculatory system within the engineered tissues, especially for microfabrication approaches. It is likely that existing models and more complex models will further our understanding of the key elements of vascular network growth, stabilization and remodeling to translate basic research principles into functional, vascularized tissue constructs for regenerative medicine applications, drug screening and disease models.
authors.affiliation: Cell and Tissue Engineering Lab, IRCCS Istituto Ortopedico Galeazzi, Milano, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Bersini
authors.affiliation: Biomaterials Innovation Research Center, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02139, USA.
authors.forename: Iman K
authors.initials: IK
authors.lastname: Yazdi
authors.affiliation: Cell and Tissue Engineering Lab, IRCCS Istituto Ortopedico Galeazzi, Milano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Talò
authors.affiliation: Biomaterials Innovation Research Center, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02139, USA.
authors.forename: Su Ryon
authors.initials: SR
authors.lastname: Shin
authors.affiliation: Cell and Tissue Engineering Lab, IRCCS Istituto Ortopedico Galeazzi, Milano, Italy; Regenerative Medicine Technologies Lab, Ente Ospedaliero Cantonale, Lugano, Switzerland; Swiss Institute for Regenerative Medicine, Lugano, Switzerland; Cardiocentro Ticino, Lugano, Switzerland. Electronic address: matteo.moretti@grupposandonato.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Moretti
authors.affiliation: Biomaterials Innovation Research Center, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, USA; Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02139, USA; Department of Physics, King Abdulaziz University, Jeddah 21569, Saudi Arabia; College of Animal Bioscience and Technology, Department of Bioindustrial Technologies, Konkuk University, Hwayang-dong, Kwangjin-gu, Seoul 143-701, Republic of Korea. Electronic address: alik@bwh.harvard.edu.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
mesh_terms: D000818:Animals; D002460:Cell Line; D060833:Cellular Microenvironment / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D051379:Mice; D008833:Microcirculation / Q000502:physiology*; D055806:Microvessels / Q000166:cytology / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods*
keywords: Cell-cell interactions; Cell-matrix interactions; Endothelium; Extracellular matrix; Microenvironment; Microfabrication; Microfluidics; Microvascular network