Related Experiment Video
Updated: Aug 14, 2026
10:48
Generation of Human Motor Units with Functional Neuromuscular Junctions in Microfluidic Devices
Published on: September 7, 2021
Modular Tissue-Engineered Motor Units Featuring Spinal Motor Neurons Innervating Self-Assembled Myofiber Bundles
Melanie C Hilman1,2,3, Elizabeth N Krizman1,2, Foteini Mourkioti4,5,6
1Center For Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Macromolecular Bioscience
|August 13, 2026
Summary
Researchers biofabricated centimeter-scale Tissue Engineered Motor Units (TEMUs) with aligned myofibers and motor neurons. Innervation significantly improved myofiber maturation and function, offering a 3D platform for studying muscle development and potential implants.
Area of Science:
- Muscle physiology and tissue engineering
- Neuroscience and developmental biology
- Biomaterials and regenerative medicine
Background:
- Muscle contraction relies on motor units, comprising muscle fibers and motor neurons.
- Tissue engineering aims to repair neuromuscular injuries by replicating native muscle architecture.
- Innervation's crucial role in myofiber development is often underestimated in current strategies.
Purpose of the Study:
- To biofabricate pre-innervated 3D bundles of myofibers, termed Tissue Engineered Motor Units (TEMUs).
- To replicate in vivo muscle architecture more closely than previous 2D models.
- To investigate the impact of innervation on myofiber maturation and function in a 3D engineered construct.
Main Methods:
- Developed a methodology for centimeter-scale TEMUs using aligned myofiber bundles in collagenous hydrogel.
- Utilized a polydimethylsiloxane micro-channel system for myoblast alignment and self-assembly.
- Integrated spinal motor neurons and their axons for innervation of the engineered muscle constructs.
Main Results:
- Innervation by motor neurons and axonal integration significantly enhanced myofiber maturation and contractility.
- Achieved centimeter-scale (≥8 cm) modular myofiber bundles, scalable for larger constructs.
- Demonstrated improved myocyte fusion and sarcomere formation in innervated TEMUs.
Conclusions:
- TEMUs provide a biofidelic 3D platform for studying innervation's role in muscle development and function.
- The scalable biofabrication protocol supports the creation of large-scale engineered muscle tissues.
- TEMUs hold potential as implantable composite tissues for muscle replacement after trauma.
Related Concept Videos
01:13Motor Units
The motor unit is a fundamental component of the neuromuscular system and plays a crucial role in coordinating muscle contractions. It consists of a somatic motor neuron, which connects and controls multiple skeletal muscle fibers, forming a single functional segment. The axon of the motor neuron branches out and establishes synaptic connections known as neuromuscular junctions with individual muscle fibers within the motor unit.
Motor units come in different sizes, with smaller units...
Motor units come in different sizes, with smaller units...
00:46Motor Units
A motor unit consists of two main components: a single efferent motor neuron (i.e., a neuron that carries impulses away from the central nervous system) and all of the muscle fibers it innervates. The motor neuron may innervate multiple muscle fibers, which are single cells, but only one motor neuron innervates a single muscle fiber.
01:13Microscopic Anatomy of Skeletal Muscles
Skeletal muscle cells, also called muscle fibers, are distinctly elongated, multi-nucleated, slender biological units. They are packed with specialized structures designed to facilitate their primary function, which is contraction.
The muscle sarcolemma is a plasma membrane enclosing each muscle cell that conducts electrical signals called action potentials. The sarcolemma extends into the cell to form T-tubules, ensuring the neural impulses are uniformly distributed across the entire muscle...
The muscle sarcolemma is a plasma membrane enclosing each muscle cell that conducts electrical signals called action potentials. The sarcolemma extends into the cell to form T-tubules, ensuring the neural impulses are uniformly distributed across the entire muscle...
01:13Formation of Muscle Fibers from Myoblasts
De novo myogenesis, or the formation of muscle fibers, begins during the early embryonic stages. The skeletal muscle is formed from somites– blocks of embryonic cell layers. The somites are further divided into dermatomes, myotomes, sclerotomes, and syndetomes. Among these, the myotomes give rise to muscle fibers.
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription factors...
Muscle progenitor cells (MPCs) are formed from the myotomes. MPCs express genes that encode the transcription factors Pax3 and Pax7. Along with Pax 3/7, other transcription factors...
01:20Motor Unit Stimulation
When the neuron of a motor unit fires an action potential, it triggers a series of events, leading to a twitch contraction in the muscle fibers. The process of excitation-contraction coupling is crucial in relaying the action potential to the muscle fibers.
The latent period of contraction marks the onset of excitation-contraction coupling, when the action potential propagates across the sarcolemma, preparing the muscle fibers for contraction. As the fibers enter the contraction phase, the...
The latent period of contraction marks the onset of excitation-contraction coupling, when the action potential propagates across the sarcolemma, preparing the muscle fibers for contraction. As the fibers enter the contraction phase, the...
01:19The Neuromuscular Junction
The nervous system consists of complex motor neuron circuits, including upper motor neurons originating from the cerebral cortex and lower motor neurons starting in the spinal cord, coordinating both voluntary and involuntary movements. Among these, somatic motor neurons activate skeletal muscles and are classified into alpha, beta, and gamma types. Alpha neurons are vital for voluntary movement coordination, while gamma neurons adjust muscle spindle sensitivity, and the function of beta...