Dataset Information

FITC-Dextran Release from Cell-Embedded Fibrin Hydrogels.

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.

SUBMITTER: Lepsky VR

PROVIDER: S-EPMC7926394 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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FITC-Dextran Release from Cell-Embedded Fibrin Hydrogels.

Lepsky Viki Raz VR Natan Sari S Tchaicheeyan Oren O Kolel Avraham A Zussman Merav M Zilberman Meital M Lesman Ayelet A

Biomolecules 20210223 2

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 hy ...[more]

PMID: 33672379

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Project description:Stem cells are a vital component of regenerative medicine therapies, however, only a fraction of stem cells delivered to the central nervous system following injury survive the inflammatory environment. Previously, we showed that subcutaneous preconditioning of neural stem cell (NSC) embedded hydrogels for 28 days improved spinal cord injury (SCI) functional outcomes over controls. Here, we investigated the mechanism of subcutaneous preconditioning of NSC-embedded hydrogels, with and without the known neurogenic cue, interferon gamma (IFN-γ), for 3, 14, or 28 days to refine and identify subcutaneous preconditioning conditions by measurement of neurogenic markers and cytokines. Studying the preconditioning mechanism, we found that subcutaneous foreign body response (FBR) associated cytokines infiltrated the scaffold in groups with and without NSCs, with time point effects. A pro-inflammatory environment with upregulated interleukin (IL)-6, IL-10, macrophage inflammatory protein (MIP)-1, MIP-2, IFN-γ-inducible protein 10 (IP-10), tumor necrosis factor-α (TNF-α), and IL-12p70 was observed on day 3. By 14 and 28 days, there was an increase in pro-regenerative cytokines (IL-13, IL-4) along with pro-inflammatory markers IL-1β, IP-10, and RANTES (regulated on activation, normal T cell expressed, and secreted) potentially part of the mechanism that had an increased functional outcome in SCI. Coinciding with changes in cytokines, the macrophage population increased over time from 3 to 28 days, whereas neutrophils peaked at 3 days with a significant decrease at later time points. Expression of the neuronal marker βIII tubulin in differentiating NSCs was supported at 3 days in the presence of soluble and immobilized IFN-γ and at 14 days by immobilized IFN-γ only, but it was greatly attenuated in all conditions at 28 days, partially because of dilution via host cell infiltration. We conclude that subcutaneously incubating NSC seeded scaffolds for 3 or 14 days could act as host specific preconditioning through exposure to FBR while retaining βIII tubulin expression of NSCs to further improve the SCI functional outcome observed with 28 day subcutaneous incubation.

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Dataset Information

FITC-Dextran Release from Cell-Embedded Fibrin Hydrogels.

Publications

FITC-Dextran Release from Cell-Embedded Fibrin Hydrogels.

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