Human Corneal Fibroblast Pattern Evolution and Matrix Synthesis on Mechanically Biased Substrates

Ramin Zareian, Monica E. Susilo, Jeffrey A. Paten, James P. McLean, Joseph Hollmann, Dimitrios Karamichos, Conor S. Messer, Dhananjay T. Tambe, Nima Saeidi, James D. Zieske, Jeffrey W. Ruberti

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


In a fibroblast colony model of corneal stromal development, we asked how physiological tension influences the patterning dynamics of fibroblasts and the orientation of deposited extracellular matrix (ECM). Using long-term live-cell microscopy, enabled by an optically accessible mechanobioreactor, a primary human corneal fibroblast colony was cultured on three types of substrates: a mechanically biased, loaded, dense, disorganized collagen substrate (LDDCS), a glass coverslip, and an unloaded, dense, disorganized collagen substrate (UDDCS). On LDDCS, fibroblast orientation and migration along a preferred angle developed early, cell orientation was correlated over long distances, and the colony pattern was stable. On glass, fibroblast orientation was poorly correlated, developed more slowly, and colony patterns were metastable. On UDDCS, cell orientation was correlated over shorter distances compared with LDDCS specimens. On all substrates, the ECM pattern reflected the cell pattern. In summary, mechanically biasing the collagen substrate altered the early migration behavior of individual cells, leading to stable emergent cell patterning, which set the template for newly synthesized ECM.

Original languageEnglish
Pages (from-to)1204-1217
Number of pages14
JournalTissue Engineering - Part A
Issue number19-20
StatePublished - 1 Oct 2016


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