Fibrin degradation enhances vascular smooth muscle cell proliferation and matrix deposition in fibrin-based tissue constructs fabricated in vitro

Katherine A. Ahmann, Justin S. Weinbaum, Sandra L. Johnson, Robert T. Tranquillo

Research output: Contribution to journalArticle

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Abstract

Completely biological tissue replacements can be fabricated by entrapping cells in a molded fibrin gel. Over time, the fibrin is degraded and replaced with cell-produced extracellular matrix. However, the relationship between fibrin degradation and matrix deposition has not been elucidated. We developed techniques to quantify fibrin degradation products (FDP) and examine plasmin activity in the conditioned medium from fibrin-based constructs. Fibrin-based tissue constructs fabricated with vascular smooth muscle cells (vSMC) were cultured for 5 weeks in the presence of varied concentrations of the fibrinolysis inhibitor ε-aminocaproic acid and cellularity, and deposited collagen and elastin were measured weekly. These data revealed that increasing concentrations of ε-aminocaproic acid led to delayed and diminished FDP production, lower vSMC proliferation, and decreased collagen and elastin deposition. FDP were shown to have a direct biological effect on vSMC cultures and vSMC within the fibrin-based constructs. Supplementing construct cultures with 250 or 500μg/mL FDP led to 30% higher collagen deposition than the untreated controls. FDP concentrations as high as 250μg/mL were estimated to exist within the constructs, indicating that FDP generation during remodeling of the fibrin-based constructs exerted direct biological activity. These results help explain many of the positive outcomes reported with fibrin-based tissue constructs in the literature, as well as demonstrate the importance of regulating plasmin activity during their fabrication.

Original languageEnglish (US)
Pages (from-to)3261-3270
Number of pages10
JournalTissue Engineering - Part A
Volume16
Issue number10
DOIs
StatePublished - Oct 1 2010

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Cell proliferation
Fibrin
Fibrin Fibrinogen Degradation Products
Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Cell Proliferation
Tissue
Degradation
Collagen
Elastin
Aminocaproic Acid
Fibrinolysin
Acids
Bioactivity
In Vitro Techniques
Cell culture
Fibrinolysis
Conditioned Culture Medium
Gels

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Fibrin degradation enhances vascular smooth muscle cell proliferation and matrix deposition in fibrin-based tissue constructs fabricated in vitro. / Ahmann, Katherine A.; Weinbaum, Justin S.; Johnson, Sandra L.; Tranquillo, Robert T.

In: Tissue Engineering - Part A, Vol. 16, No. 10, 01.10.2010, p. 3261-3270.

Research output: Contribution to journalArticle

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