title: Matrix-bound nanovesicles within ECM bioscaffolds.
abstract: Biologic scaffold materials composed of extracellular matrix (ECM) have been used in a variety of surgical and tissue engineering/regenerative medicine applications and are associated with favorable constructive remodeling properties including angiogenesis, stem cell recruitment, and modulation of macrophage phenotype toward an anti-inflammatory effector cell type. However, the mechanisms by which these events are mediated are largely unknown. Matrix-bound nanovesicles (MBVs) are identified as an integral and functional component of ECM bioscaffolds. Extracellular vesicles (EVs) are potent vehicles of intercellular communication due to their ability to transfer RNA, proteins, enzymes, and lipids, thereby affecting physiologic and pathologic processes. Formerly identified exclusively in biologic fluids, the presence of EVs within the ECM of connective tissue has not been reported. In both laboratory-produced and commercially available biologic scaffolds, MBVs can be separated from the matrix only after enzymatic digestion of the ECM scaffold material, a temporal sequence similar to the functional activity attributed to implanted bioscaffolds during and following their degradation when used in clinical applications. The present study shows that MBVs contain microRNA capable of exerting phenotypical and functional effects on macrophage activation and neuroblastoma cell differentiation. The identification of MBVs embedded within the ECM of biologic scaffolds provides mechanistic insights not only into the inductive properties of ECM bioscaffolds but also into the regulation of tissue homeostasis.
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Luai
authors.initials: L
authors.lastname: Huleihel
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: George S
authors.initials: GS
authors.lastname: Hussey
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Juan Diego
authors.initials: JD
authors.lastname: Naranjo
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Jenna L
authors.initials: JL
authors.lastname: Dziki
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Neill J
authors.initials: NJ
authors.lastname: Turner
authors.affiliation: Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Center of Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
authors.forename: Donna B
authors.identifier: 0000-0002-1833-7010
authors.initials: DB
authors.lastname: Stolz
authors.affiliation: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA.; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Badylak
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D005109:Extracellular Matrix / Q000737:chemistry; D000067128:Extracellular Vesicles / Q000737:chemistry; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D049329:Nanostructures / Q000737:chemistry; D009696:Nucleic Acids / Q000737:chemistry; D044968:Regenerative Medicine; D013552:Swine; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D009696:Nucleic Acids; D004247:DNA
keywords: Exosomes; Extracellular Matrix (ECM); Extracellular vesicles (EV); Matrix Bound Nano Vesicles (MBV); Microvesicles (MV)