Bioengineering of physiologically functional intrinsically innervated human internal anal sphincter constructs

Area of Science:

• Regenerative Medicine
• Tissue Engineering
• Neuroscience

Background:

• Extensive muscle tissue loss or dysfunction necessitates advanced regenerative medicine strategies.
• Functional restoration of bioengineered muscle replacements requires successful innervation.
• Current methods lack effective strategies for creating innervated muscle constructs.

Purpose of the Study:

• To bioengineer functional gut smooth muscle constructs with integrated innervation.
• To utilize adult human-derived neuronal progenitor cells and smooth muscle cells.
• To assess the functional capacity and neural integration of the engineered constructs.

Main Methods:

• Isolation and culture of neuronal progenitor cells and smooth muscle cells from human intestinal tissue.
• Co-culture of these cells to form bioengineered muscle constructs.
• Characterization of construct cell types and assessment of functional responses to neurotransmitters and electrical stimulation.

Main Results:

• Engineered constructs expressed markers for smooth muscle, glial cells, and mature neurons.
• Constructs demonstrated appropriate physiological responses to neurotransmitters.
• Neural network integration was confirmed via electrical field stimulation, showing functional innervation.

Conclusions:

• Enteric neuroprogenitor cells can differentiate into neuronal populations for functional innervation.
• Bioengineered, functionally innervated muscle constructs offer a therapeutic approach for neuromuscular replacement.
• This method has broad potential for innervating various bioengineered muscle constructs beyond gut tissue.