title: A shape-controlled tuneable microgel platform to modulate angiogenic paracrine responses in stem cells.
abstract: Development of cell delivery platforms have been driven based on an empirical cytoprotective design. While cell-matrix and cell-cell interactions that influence biochemical effects beyond survival has been limited and overshadowed in an effort to incrementally improve biomimicking properties of the tissue-engineered constructs. Here we demonstrate fabrication of a shape controlled 3D type-I collagen-based microgel platform that can be tuned to modulate angiogenic paracrine- 'angiocrine' responses of human mesenchymal stem cells (hMSCs). Furthermore, these microgels were characterized as a 3D cell culture tool to assess optimal biological response as a function of cell-matrix and cell-cell interactions. Finally, optimised hMSC embedded microgels were shown to induce vascular repair and functional improvement in vivo in a mouse model of hind-limb ischemia. The approach described here in designing a tuneable cell delivery platform using naturally occurring extracellular matrix molecules highlights the need for highly customised matrices with an array of self-assembling proteins that dictate specific cell function resembling the native tissue of interest for repair.
authors.affiliation: Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland; Network of Excellence for Functional Biomaterials, National University of Ireland Galway, Galway, Ireland.
authors.forename: Dilip
authors.initials: D
authors.lastname: Thomas
authors.affiliation: Network of Excellence for Functional Biomaterials, National University of Ireland Galway, Galway, Ireland.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Fontana
authors.affiliation: Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland.
authors.forename: Xizhe
authors.initials: X
authors.lastname: Chen
authors.affiliation: Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland.
authors.forename: Clara
authors.initials: C
authors.lastname: Sanz-Nogués
authors.affiliation: Network of Excellence for Functional Biomaterials, National University of Ireland Galway, Galway, Ireland.
authors.forename: Dimitrios I
authors.initials: DI
authors.lastname: Zeugolis
authors.affiliation: Anatomy, National University of Ireland Galway, Galway, Ireland.
authors.forename: Peter
authors.initials: P
authors.lastname: Dockery
authors.affiliation: Regenerative Medicine Institute, National University of Ireland Galway, Galway, Ireland.
authors.forename: Timothy
authors.initials: T
authors.lastname: O'Brien
authors.affiliation: Network of Excellence for Functional Biomaterials, National University of Ireland Galway, Galway, Ireland. Electronic address: abhay.pandit@nuigalway.ie.
authors.forename: Abhay
authors.initials: A
authors.lastname: Pandit
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002454:Cell Differentiation; D002470:Cell Survival; D024042:Collagen Type I / Q000737:chemistry*; D005782:Gels / Q000737:chemistry; D006614:Hindlimb / Q000098:blood supply / Q000601:surgery; D006801:Humans; D007511:Ischemia / Q000628:therapy; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; D024042:Collagen Type I; D005782:Gels
keywords: Angiogenesis; Cell-factories; Customised ECM matrices; Mesenchymal stem cells; Microgels