Influence of multi-axial dynamic constraint on cell alignment and contractility in engineered tissues

Area of Science:

• Biomaterials Engineering
• Cellular Mechanics
• Tissue Engineering

Background:

• Engineered tissues require understanding of cell behavior under mechanical stimuli.
• Cell alignment and active force generation are critical for functional tissue constructs.

Purpose of the Study:

• To investigate how tissue constraint and cyclic loading affect cell alignment and force generation.
• To compare uniaxial and biaxial engineered tissue constructs.

Main Methods:

• Developed an experimental rig for uniaxial and biaxial tissue constructs.
• Utilized collagen hydrogels with contractile cells.
• Applied dynamic loading and cytochalasin D treatment.
• Employed an active modeling framework.

Main Results:

• Contractile cells dramatically increased forces in both uniaxial and biaxial constructs under dynamic loading.
• Uniaxial constraints promoted cell alignment prior to loading; biaxial constraints did not.
• Dynamic uniaxial stretching slightly increased cell alignment; biaxial stretching had no significant effect.
• Uniaxially constrained tissues generated significantly higher actively generated cell contractile stress (75%) compared to biaxially constrained tissues.

Conclusions:

• Tissue constraints critically influence cell alignment and active force generation in engineered tissues.
• Uniaxial constraints are superior for maximizing cell contractile stress in engineered tissues.
• Findings have significant implications for designing functional contractile tissue constructs.