The interplay between tissue growth and scaffold degradation in engineered tissue constructs.

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Computational Biology

Background:

• In vitro tissue engineering aims to meet the demand for replacement tissues due to degeneration and damage.
• Ensuring appropriate mechanical properties of engineered tissues for in vivo use is a critical challenge.
• Understanding cell proliferation, extracellular matrix (ECM) deposition, and scaffold degradation interplay is vital.

Purpose of the Study:

• To investigate the interplay between tissue growth and scaffold degradation in vitro using a mathematical model.
• To analyze how scaffold heterogeneity, cell-scaffold interactions, and mechanotransduction influence tissue construct evolution.
• To explore the impact of these factors on the mechanical integrity and suitability of engineered tissues for implantation.

Main Methods:

• Developed a multiphase continuum mathematical model representing cells, culture medium, scaffold, and ECM.
• Simulated tissue growth in a perfusion bioreactor system.
• Investigated the effects of differential cell-scaffold/ECM interactions, scaffold degradation, and mechanotransduction on tissue composition.

Main Results:

• Scaffold heterogeneity, derived from micro-CT scans, causes significant variations in flow-induced mechanical stimuli for cells.
• This heterogeneity leads to pronounced variations in ECM deposition.
• Cell adherence to ECM showed minimal influence, while adherence to the scaffold exaggerated scaffold heterogeneity in cell and ECM distribution.

Conclusions:

• Scaffold heterogeneity is a key factor influencing engineered tissue composition and mechanical properties.
• Cell-ECM interactions have less impact than cell-scaffold interactions on construct heterogeneity.
• Findings have significant implications for the mechanical integrity and in vivo suitability of engineered tissues.