Skeletal muscle tissue engineering: from tissue regeneration to biorobotics
image: The contraction process involves interactions between actin and myosin filaments within the sarcomeres to generate force.
Credit: Maira Z. Cordelle, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford.
Recent research has achieved significant advances in functional design, modeling, and control of biohybrid robots actuated by engineered skeletal muscle tissues. Nevertheless, replicating the nuanced force modulation and adaptive compliance of natural muscle movement remains challenging, often relying on iterative trial-and-error in scaffold design, cell maturation, and stimulation protocols. This process consumes substantial time and resources. “Optimizing the interplay between scaffold stiffness (10–20 kPa), anisotropic cell alignment, and physiologically relevant mechanical/electrical stimulation is critical to achieve functional maturation,” emphasized the authors. Computational modeling integrating (a) hyperelastic behavior of ECM-mimicking hydrogels, (b) dynamic strain responses during contraction (up to 40% deformation), and (c) force transmission across biohybrid interfaces could streamline development. “Combining computational design with advanced bioreactors will accelerate the creation of robust bioactuators, avoiding costly experimental cycles,” stated Cordelle et al. They proposed biohybrid systems wherein engineered muscle bundles—differentiated from iPSCs or myoblasts on aligned electrospun scaffolds—are integrated into soft robotic frameworks, leveraging finite element analysis to predict contractile performance and deformation kinematics.
Engineered muscles can be fabricated using diverse biomaterials (e.g., decellularized ECM, fibrin, PEGDA) and techniques ranging from electrospinning to 3D bioprinting. 3D bioprinting enables precise spatial patterning of cell-laden bioinks, allowing complex, vascular-mimetic geometries and embedded microchannels for nutrient perfusion. “Bioprinting facilitates the incorporation of neuronal networks and vascular precursors within constructs, enabling integrated sensing/actuation and enhancing tissue viability,” noted the review. Soft robotic integration further benefits from flexible bioreactors that apply multiaxial mechanical cues (e.g., stretching, compression) to mature tissues in vitro.
Current biohybrid actuators demonstrate promising dexterity: Antagonistic muscle pairs enable articulated gripping (90° rotation), while bundled myotubes power locomotion in walkers (fine turning) and swimmers (800 µm/s). Simplified ON–OFF electrical or optical control sustains stable contractions in lightweight systems. "These actuators successfully manipulate delicate objects and achieve directional mobility but exhibit limited force output (<1 kPa) and endurance due to absent vascularization," the authors observed. Challenges persist in scaling constructs beyond centimeters, grasping heavy/slippery objects, and preventing mechanical interference between adjacent units. Future work requires standardized benchmarks and in-depth modeling of muscle-robot interaction dynamics to overcome nonlinearities in force transmission and metabolic constraints.
Authors of the paper include Maira Z. Cordelle, Sarah J. B. Snelling, Pierre-Alexis Mouthuy.
This work has been completed with the financial support of the United Kingdom’s Medical Research Council and the United Kingdom’s Engineering and Physical Sciences Research Council (reference EP/S003509/1). This project has also been supported by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC).
The paper, “Skeletal Muscle Tissue Engineering: From Tissue Regeneration to Biorobotics” was published in the journal Cyborg and Bionic Systems on May 15, 2025, at DOI: 10.34133/cbsystems.0279.