Spontaneous Helical Alignment of Smooth Muscle Cells to Form a Medial Layer for Engineered Microvasculature

Area of Science:

• Biomedical Engineering
• Vascular Biology
• Tissue Engineering

Background:

• Small resistance vessels (SRVs) are critical for regulating vascular resistance and tissue perfusion.
• Current engineered SRVs lack the helical smooth muscle cell (SMC) layer essential for contractile function.
• Existing engineered vasculature often fails to replicate the architecture and vasoreactivity of natural SRVs.

Purpose of the Study:

• To develop a method for engineering SRV-scale vasculature with aligned, contractile SMCs.
• To investigate fabrication parameters influencing SMC alignment and phenotype in engineered SRVs.
• To establish a foundation for creating functional, vasoreactive engineered vascular constructs.

Main Methods:

• Seeding SMCs onto the walls of SRV-sized hydrogel channels.
• Optimizing fabrication parameters (e.g., extracellular matrix composition, seeding density, channel diameter) to promote spontaneous SMC alignment.
• Assessing SMC alignment, morphology, and contractile function (e.g., response to endothelin-1).

Main Results:

• Achieved spontaneous helical alignment of SMCs within SRV-sized hydrogel channels without topographical patterning.
• Demonstrated that alignment angle is sensitive to fabrication parameters.
• Confirmed that aligned SMCs exhibit contractile phenotype and respond to vasoconstrictors like endothelin-1 (ET-1).

Conclusions:

• Appropriate fabrication parameters can induce spontaneous helical alignment of SMCs in engineered SRVs.
• This method establishes an aligned, contractile SMC layer, crucial for vasoreactivity.
• Represents a significant advancement toward engineering functional SRVs that mimic natural vessels.