Abstract
Fibrin hydrogel is a central biological material in tissue engineering and drug delivery applications. As such, fibrin is typically combined with cells and biomolecules targeted to the regenerated tissue. Previous studies have analyzed the release of different molecules from fibrin hydrogels; however, the effect of embedded cells on the release profile has yet to be quantitatively explored. This study focused on the release of Fluorescein isothiocyanate (FITC)-dextran (FD) 250 kDa from fibrin hydrogels, populated with different concentrations of fibroblast or endothelial cells, during a 48-h observation period. The addition of cells to fibrin gels decreased the overall release by a small percentage (by 7–15% for fibroblasts and 6–8% for endothelial cells) relative to acellular gels. The release profile was shown to be modulated by various cellular activities, including gel degradation and physical obstruction to diffusion. Cell-generated forces and matrix deformation (i.e., densification and fiber alignment) were not found to significantly influence the release profiles. This knowledge is expected to improve fibrin integration in tissue engineering and drug delivery applications by enabling predictions and ways to modulate the release profiles of various biomolecules.
Highlights
Hydrogels, i.e., polymeric water-swollen and cross-linked networks [1], have been explored as attractive carriers for controlled drug delivery applications due to their biochemical and transport properties [2,3]
Jeon et al [8] reported on the release of basic fibroblast growth factors from fibrin gels controlled by heparin and different concentrations of thrombin and fibrinogen
The fit of the experimental data was performed according to the two-stage desorption addition of fibroblast cells to the gel reduced release profile by about
Summary
I.e., polymeric water-swollen and cross-linked networks [1], have been explored as attractive carriers for controlled drug delivery applications due to their biochemical and transport properties [2,3] Such drug-eluting hydrogels are designed to maintain drug concentrations at effective levels over a prolonged period of time [4]. Tredwell et al [6] demonstrated the feasibility and effectiveness of the controlled release of cefazolin antibiotic over a 2-day period from fibrin sealant clots in vitro, with a sharp burst phase of release over the first 6–8 h, followed by a sustained release over the following 16 h This system supports possible applications in orthopedic surgeries.
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