title: In Vitro Multitissue Interface Model Supports Rapid Vasculogenesis and Mechanistic Study of Vascularization across Tissue Compartments.
abstract: A significant challenge facing tissue engineers is the design and development of complex multitissue systems, including vascularized tissue-tissue interfaces. While conventional in vitro models focus on either vasculogenesis (de novo formation of blood vessels) or angiogenesis (vessels sprouting from existing vessels or endothelial monolayers), successful therapeutic vascularization strategies will likely rely on coordinated integration of both processes. To address this challenge, we developed a novel in vitro multitissue interface model in which human endothelial colony forming cell (ECFC)-encapsulated tissue spheres are embedded within a surrounding tissue microenvironment. This highly reproducible approach exploits biphilic surfaces (nanostructured surfaces with distinct superhydrophobic and hydrophilic regions) to (i) support tissue compartments with user-specified matrix composition and physical properties as well as cell type and density and (ii) introduce boundary conditions that prevent the cell-mediated tissue contraction routinely observed with conventional three-dimensional monodispersion cultures. This multitissue interface model was applied to test the hypothesis that independent control of cell-extracellular matrix (ECM) and cell-cell interactions would affect vascularization within the tissue sphere as well as across the tissue-tissue interface. We found that high-cell-density tissue spheres containing 5 × 10(6) ECFCs/mL exhibit rapid and robust vasculogenesis, forming highly interconnected, stable (as indicated by type IV collagen deposition) vessel networks within only 3 days. Addition of adipose-derived stromal cells (ASCs) in the surrounding tissue further enhanced vasculogenesis within the sphere as well as angiogenic vessel elongation across the tissue-tissue boundary, with both effects being dependent on the ASC density. Overall, results show that the ECFC density and ECFC-ASC crosstalk, in terms of paracrine and mechanophysical signaling, are critical determinants of vascularization within a given tissue compartment and across tissue interfaces. This new in vitro multitissue interface model and the associated mechanistic insights it yields provide guiding principles for the design and optimization of multitissue vascularization strategies for research and clinical applications.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Buno
authors.affiliation: School of Mechanical Engineering, Purdue University , West Lafayette, Indiana 47907, United States.|Birck Nanotechnology Center, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Mechanical Engineering, Purdue University , West Lafayette, Indiana 47907, United States.|Birck Nanotechnology Center, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Weibel
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Stephanie N
authors.initials: SN
authors.lastname: Thiede
authors.affiliation: School of Mechanical Engineering, Purdue University , West Lafayette, Indiana 47907, United States.|Birck Nanotechnology Center, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Suresh V
authors.initials: SV
authors.lastname: Garimella
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University , West Lafayette, Indiana 47907, United States.|Department of Pediatrics, Indiana University School of Medicine , Indianapolis, Indiana 46202, United States.|Herman B Wells Center for Pediatric Research, Indiana University School of Medicine , Indianapolis, Indiana 46202, United States.|Department of Biochemistry and Molecular Biology, Indiana University School of Medicine , Indianapolis, Indiana 46202, United States.
authors.forename: Mervin C
authors.initials: MC
authors.lastname: Yoder
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University , West Lafayette, Indiana 47907, United States.|Department of Basic Medical Sciences, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Sherry L
authors.initials: SL
authors.lastname: Voytik-Harbin
mesh_terms: D002454:Cell Differentiation; D042783:Endothelial Cells; D006801:Humans; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D023822:Tissue Engineering
keywords: adipose-derived stromal cells (ASCs); collagen oligomers; endothelial colony forming cells (ECFCs); mechanobiology; multitissue interface; tissue engineering; vascularization