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Impact of collagen structure on matrix trafficking by human fibroblasts
Author(s) -
Abraham Leah C.,
Vorrasi John,
Kaplan David L.
Publication year - 2004
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.30057
Subject(s) - extracellular matrix , fibroblast , matrix metalloproteinase , matrix (chemical analysis) , materials science , type i collagen , in vitro , collagen receptor , in vivo , microbiology and biotechnology , biomaterial , cell culture , cell , biophysics , chemistry , biochemistry , biology , cell adhesion , nanotechnology , endocrinology , composite material , genetics
Biodegradation of collagen biomaterial matrices and the deposition of new collagen extracellular matrix (ECM) are critical to the integration of in vitro bioengineered materials and tissues in vivo . In previous studies, we observed significant impact of collagen matrix structure on primary lung fibroblast behavior in vitro . In the present work, to begin to understand the mechanistic basis for our previous observation, the response of human fibroblasts (IMR‐90) to the structural state of collagen matrices was studied with respect to cell proliferation, cell morphology, β‐galactosidase level, and transcript content for collagen (Col‐1), matrix metalloproteinases (MMP‐1, MMP‐2), tissue inhibitors of matrix metalloproteinase (TIMP‐1 and TIMP‐2). Collagen digestion was assessed quantitatively by uptake of collagen‐coated fluorescent beads incorporated in the preformed collagen matrix. Transcript levels related to the deposition of new ECM proteins varied as a function of the structure of the collagen matrix presented to the cells. Col‐1 expression was 2‐fold higher and expression for MMP‐1, MMP‐2, TIMP‐1, and TIMP‐2 increased for cells when grown on 156 μg/cm 2 denatured collagen compared with cells grown on tissue culture (TC) plastic. On 156 μg/cm 2 nondenatured (native) collagen, Col‐1 expression was decreased by half and MMP‐2 was increased by 2.5‐fold compared with cells grown on TC plastic. On 78 μg/cm 2 denatured collagen, Col‐1 expression was 80% whereas the MMPs and TIMPs were increased by 1.25‐ to 2‐fold compared with cells grown on TC plastic. On 78 μg/cm 2 nondenatured collagen expression of all 5 transcripts was reduced 60‐90% of the levels determined for the cells grown on TC plastic. Cell viability, based on cell morphology and β‐galactosidase activity, was improved on the denatured collagen. A higher level of collagen matrix incorporation was observed for cells grown on denatured collagen than on nondenatured collagen or TC plastic. These data suggest that tissue engineering matrices incorporating denatured collagen may promote more active remodeling toward new ECM in comparison to cells grown on nondenatured collagen or cells grown on TC plastic. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 70A: 39–48, 2004