Simulation and Fabrication of Stronger, Larger, and Faster Walking Biohybrid Machines

Advancing biologically driven soft robotics and actuators will involve employing different scaffold geometries and cellular constructs to enable a controllable emergence for increased production of force. By using hydrogel scaffolds and muscle tissue, soft biological robotic actuators that are capable of motility have been successfully engineered with varying morphologies. Having the flexibility of altering geometry while ensuring tissue viability can enable advancing functional output from these machines through the implementation of new construction concepts and fabrication approaches. This study reports a forward engineering approach to computationally design the next generation of biological machines via direct numerical simulations. This was subsequently followed by fabrication and characterization of high force producing biological machines. These biological machines show millinewton forces capable of driving locomotion at speeds above 0.5 mm s−1. It is important to note that these results are predicted by computational simulations, ultimately showing excellent agreement of the predictive models and experimental results, further providing the ability to forward design future generations of these biological machines. This study aims to develop the building blocks and modular technologies capable of scaling force and complexity of these devices for applications toward solving real world problems in medicine, environment, and manufacturing.

[1]  Victoria A. Webster,et al.  Effect of actuating cell source on locomotion of organic living machines with electrocompacted collagen skeleton , 2016, Bioinspiration & biomimetics.

[2]  R. Bashir,et al.  Creating Living Cellular Machines , 2013, Annals of Biomedical Engineering.

[3]  Shoji Takeuchi,et al.  Three-dimensional neuron-muscle constructs with neuromuscular junctions. , 2013, Biomaterials.

[4]  Ritu Raman,et al.  Optogenetic skeletal muscle-powered adaptive biological machines , 2016, Proceedings of the National Academy of Sciences.

[5]  R. Bashir,et al.  Investigating the Life Expectancy and Proteolytic Degradation of Engineered Skeletal Muscle Biological Machines , 2017, Scientific Reports.

[6]  W. Herzog,et al.  Force enhancement following stretching of skeletal muscle: a new mechanism. , 2002, The Journal of experimental biology.

[7]  Jan P Stegemann,et al.  Influence of thrombin concentration on the mechanical and morphological properties of cell-seeded fibrin hydrogels. , 2007, Acta biomaterialia.

[8]  Austen C. Duffy,et al.  Where do computational mathematics and computational statistics converge? , 2014 .

[9]  Megan L. McCain,et al.  A tissue-engineered jellyfish with biomimetic propulsion , 2012, Nature Biotechnology.

[10]  Rashid Bashir,et al.  Multi-material bio-fabrication of hydrogel cantilevers and actuators with stereolithography. , 2012, Lab on a chip.

[11]  Benjamin Wu,et al.  Modulation of 3D fibrin matrix stiffness by intrinsic fibrinogen-thrombin compositions and by extrinsic cellular activity. , 2009, Tissue engineering. Part A.

[12]  R. Bashir,et al.  Development of Miniaturized Walking Biological Machines , 2012, Scientific Reports.

[13]  R. Fitts,et al.  The determinants of skeletal muscle force and power: their adaptability with changes in activity pattern. , 1991, Journal of biomechanics.

[14]  R. Bashir,et al.  Directed cell growth and alignment on protein-patterned 3D hydrogels with stereolithography , 2012 .

[15]  M. Shikida,et al.  Assembly of skeletal muscle cells on a Si-MEMS device and their generative force measurement , 2010, Biomedical microdevices.

[16]  M Calisti,et al.  Fundamentals of soft robot locomotion , 2017, Journal of The Royal Society Interface.

[17]  D. Mooney,et al.  Hydrogels for tissue engineering: scaffold design variables and applications. , 2003, Biomaterials.

[18]  M. Peckham Engineering a multi‐nucleated myotube, the role of the actin cytoskeleton , 2008, Journal of microscopy.

[19]  Lauran R. Madden,et al.  Physiology and metabolism of tissue-engineered skeletal muscle , 2014, Experimental biology and medicine.

[20]  J. Hubbell,et al.  Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering , 2005, Nature Biotechnology.

[21]  Abhishek Tondon,et al.  The Direction of Stretch-Induced Cell and Stress Fiber Orientation Depends on Collagen Matrix Stress , 2014, PloS one.

[22]  Kyongbum Lee,et al.  Vascularization strategies for tissue engineering. , 2009, Tissue engineering. Part B, Reviews.

[23]  B. Williams,et al.  A self-propelled biohybrid swimmer at low Reynolds number , 2014, Nature Communications.

[24]  C. Tseng,et al.  Submicron-grooved culture surface extends myotube length by forming parallel and elongated motif , 2013 .

[25]  Adam J. Engler,et al.  Myotubes differentiate optimally on substrates with tissue-like stiffness , 2004, The Journal of cell biology.

[26]  Z Q Liu,et al.  Scale space approach to directional analysis of images. , 1991, Applied optics.

[27]  Ritu Raman,et al.  Three-dimensionally printed biological machines powered by skeletal muscle , 2014, Proceedings of the National Academy of Sciences.

[28]  Yuhui Li,et al.  Patterning Cellular Alignment through Stretching Hydrogels with Programmable Strain Gradients. , 2015, ACS applied materials & interfaces.

[29]  Jennifer M. Rieser,et al.  Tail use improves performance on soft substrates in models of early vertebrate land locomotors , 2016, Science.

[30]  Adam W Feinberg,et al.  Engineered skeletal muscle tissue for soft robotics: fabrication strategies, current applications, and future challenges. , 2014, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[31]  W Herzog,et al.  Length dependence of active force production in skeletal muscle. , 1999, Journal of applied physiology.

[32]  Mitsuo Umezu,et al.  Fabrication of Pulsatile Cardiac Tissue Grafts Using a Novel 3-Dimensional Cell Sheet Manipulation Technique and Temperature-Responsive Cell Culture Surfaces , 2002, Circulation research.

[33]  Paolo Dario,et al.  Biohybrid actuators for robotics: A review of devices actuated by living cells , 2017, Science Robotics.

[34]  Rashid Bashir,et al.  “Living” Microvascular Stamp for Patterning of Functional Neovessels; Orchestrated Control of Matrix Property and Geometry , 2012, Advanced materials.

[35]  Nenad Bursac,et al.  Mesoscopic hydrogel molding to control the 3D geometry of bioartificial muscle tissues , 2009, Nature Protocols.

[36]  Jeroen Rouwkema,et al.  Supply of Nutrients to Cells in Engineered Tissues , 2009, Biotechnology & genetic engineering reviews.

[37]  Ali Khademhosseini,et al.  Directed 3D cell alignment and elongation in microengineered hydrogels. , 2010, Biomaterials.

[38]  Rachelle N. Palchesko,et al.  Development of Polydimethylsiloxane Substrates with Tunable Elastic Modulus to Study Cell Mechanobiology in Muscle and Nerve , 2012, PloS one.

[39]  Ali Khademhosseini,et al.  3D biofabrication strategies for tissue engineering and regenerative medicine. , 2014, Annual review of biomedical engineering.

[40]  Ritu Raman,et al.  A modular approach to the design, fabrication, and characterization of muscle-powered biological machines , 2017, Nature Protocols.

[41]  Takehiko Kitamori,et al.  An actuated pump on-chip powered by cultured cardiomyocytes. , 2006, Lab on a chip.

[42]  E. Kempner,et al.  A physiological role for titin and nebulin in skeletal muscle , 1986, Nature.

[43]  Jeong-Woo Choi,et al.  Phototactic guidance of a tissue-engineered soft-robotic ray , 2016, Science.

[44]  A. Knicker,et al.  High force development augments skeletal muscle signalling in resistance exercise modes equalized for time under tension , 2014, Pflügers Archiv: European Journal of Physiology.

[45]  Ron Weiss,et al.  Formation and optogenetic control of engineered 3D skeletal muscle bioactuators. , 2012, Lab on a chip.

[46]  G. Piazzesi,et al.  Force generation by skeletal muscle is controlled by mechanosensing in myosin filaments , 2015, Nature.