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Effect of nordihydroguaiaretic acid cross-linking on fibrillar collagen: in vitro evaluation of fibroblast adhesion strength and migration

1 Department of Chemical and Biomedical Engineering, University of South Florida, Tampa, FL 33620, USA
2 MiMedx Group, Inc., Marietta, GA 30062, USA
3 Department of Mechanical Engineering, University of South Florida, Tampa, FL 33620, USA

Topical Section: Cell and Tissue Engineering

Fixation is required to reinforce reconstituted collagen for orthopedic bioprostheses such as tendon or ligament replacements. Previous studies have demonstrated that collagen fibers cross-linked by the biocompatible dicatechol nordihydroguaiaretic acid (NDGA) have mechanical strength comparable to native tendons. This work focuses on investigating fibroblast behavior on fibrillar and NDGA cross-linked type I collagen to determine if NDGA modulates cell adhesion, morphology, and migration. A spinning disk device that applies a range of hydrodynamic forces under uniform chemical conditions was employed to sensitively quantify cell adhesion strength, and a radial barrier removal assay was used to measure cell migration on films suitable for these quantitative in vitro assays. The compaction of collagen films, mediated by the drying and cross-linking fabrication process, suggests a less open organization compared to native fibrillar collagen that likely allowed the collagen to form more inter-chain bonds and chemical links with NDGA polymers. Fibroblasts strongly adhered to and migrated on native and NDGA cross-linked fibrillar collagen; however, NDGA modestly reduced cell spreading, adhesion strength and migration rate. Thus, it is hypothesized that NDGA cross-linking masked some adhesion receptor binding sites either physically, chemically, or both, thereby modulating adhesion and migration. This alteration in the cell-material interface is considered a minimal trade-off for the superior mechanical and compatibility properties of NDGA cross-linked collagen compared to other fixation approaches.
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Keywords collagen; cell adhesion; nordihydroguaiaretic acid; tendon replacement; orthopedic tissue engineering

Citation: Ana Y. Rioja, Maritza Muniz-Maisonet, Thomas J. Koob, Nathan D. Gallant. Effect of nordihydroguaiaretic acid cross-linking on fibrillar collagen: in vitro evaluation of fibroblast adhesion strength and migration. AIMS Bioengineering, 2017, 4(2): 300-317. doi: 10.3934/bioeng.2017.2.300


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Copyright Info: 2017, Nathan D. Gallant, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

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