title: Dynamic assembly of ultrasoft colloidal networks enables cell invasion within restrictive fibrillar polymers.
abstract: In regenerative medicine, natural protein-based polymers offer enhanced endogenous bioactivity and potential for seamless integration with tissue, yet form weak hydrogels that lack the physical robustness required for surgical manipulation, making them difficult to apply in practice. The use of higher concentrations of protein, exogenous cross-linkers, and blending synthetic polymers has all been applied to form more mechanically robust networks. Each relies on generating a smaller network mesh size, which increases the elastic modulus and robustness, but critically inhibits cell spreading and migration, hampering tissue regeneration. Here we report two unique observations; first, that colloidal suspensions, at sufficiently high volume fraction (ϕ), dynamically assemble into a fully percolated 3D network within high-concentration protein polymers. Second, cells appear capable of leveraging these unique domains for highly efficient cell migration throughout the composite construct. In contrast to porogens, the particles in our system remain embedded within the bulk polymer, creating a network of particle-filled tunnels. Whereas this would normally physically restrict cell motility, when the particulate network is created using ultralow cross-linked microgels, the colloidal suspension displays viscous behavior on the same timescale as cell spreading and migration and thus enables efficient cell infiltration of the construct through the colloidal-filled tunnels.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Douglas
authors.affiliation: School of Physics, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: Alexandros A
authors.initials: AA
authors.lastname: Fragkopoulos
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332.|School of Physics, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Gaines
authors.affiliation: Schmid College of Science and Technology, Chapman University, Orange, CA 92866.
authors.forename: L Andrew
authors.initials: LA
authors.lastname: Lyon
authors.affiliation: School of Physics, Georgia Institute of Technology, Atlanta, GA 30332.
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernandez-Nieves
authors.affiliation: Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908 thomas.barker@virginia.edu.
authors.forename: Thomas H
authors.identifier: 0000-0002-3218-8111
authors.initials: TH
authors.lastname: Barker
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002465:Cell Movement; D003102:Colloids / Q000737:chemistry*; D005337:Fibrin / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry; D051379:Mice; D041681:NIH 3T3 Cells; D011108:Polymers / Q000737:chemistry; D044968:Regenerative Medicine; D013917:Thrombin / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D003102:Colloids; D020100:Hydrogels; D011108:Polymers; D005337:Fibrin; D013917:Thrombin
keywords: cell migration; colloidal assemblies; fibrin; microgels; porosity