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Fibroblast response to interstitial flow: A state-of-the-art review.

Liu Dan1, Chee-Kai Chua, Kah-Fai Leong

  • 1Nanyang Technological University, Singapore, Singapore. liud0008@ntu.edu.sg

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Interstitial flow (IF) regulates fibroblast behavior through intracellular and cellular mechanisms. Optimizing IF in tissue engineering (TE) requires considering multiple system factors for effective cell and tissue function.

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Area of Science:

  • Biomedical Engineering
  • Cell Biology
  • Tissue Engineering

Background:

  • Interstitial flow (IF) is a critical regulator of cell and tissue function.
  • IF influences biochemical and biophysical cues in the cellular microenvironment.
  • Tissue engineering (TE) commonly employs IF to modulate cellular responses.

Purpose of the Study:

  • To elucidate the regulatory mechanisms of IF on fibroblasts.
  • To detail fibroblast responses to IF at intracellular and cellular levels.
  • To identify challenges and considerations for IF application in fibroblast-involved TE.

Main Methods:

  • Review of existing literature on IF and fibroblast interactions.
  • Analysis of intracellular mechanisms (e.g., calcium signaling, protein secretion).
  • Examination of cellular responses (e.g., proliferation, migration, differentiation).

Main Results:

  • IF affects fibroblast growth via intracellular pathways like calcium signaling and protein secretion.
  • Cellular-level responses include autocrine/paracrine signaling, proliferation, differentiation, alignment, adhesion, and migration.
  • A key challenge is microlevel determination of flow and cell growth in 3D environments.

Conclusions:

  • IF significantly impacts fibroblast behavior at multiple levels.
  • Optimizing IF in TE requires careful consideration of perfusate composition, flow, nutrient supply, signaling molecules, scaffold properties, and fibroblast type.
  • Further research is needed to overcome challenges in microlevel monitoring for effective TE applications.