期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 5, 页码 885-890出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1607350114
关键词
fibrin; microgels; colloidal assemblies; porosity; cell migration
资金
- Department of Defense [W81XWH-15-1-0485]
- National Institutes of Health [R01HL130918]
- National Science Foundation [DMR-1609841]
- American Heart Association
- National Science Foundation (NSF) [NSF DGE 0965945]
- Parker H. Petit Institute for Bioengineering and Bioscience
- Georgia Tech/Children's Healthcare of Atlanta (GT/CHOA) Center for Pediatric Nanomedicine
- Direct For Mathematical & Physical Scien
- Division Of Materials Research [1609841] Funding Source: National Science Foundation
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 (phi), 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.
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