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1. Progress in Bioinspired Dry and Wet Gradient Materials from Design Principles to Engineering Applications

   https://doi.org/https://doi.org/10.1016/j.isci.2020.101749  

   Dong, X. ; Zhao, H. ; Li, J. ; Tian, Y. ; Zeng, H. ; Ramos, M.A. ; Hu, T.S. ; Xu, Q. ( November 2020 , iScience)

   null (Ed.)

   Nature does nothing in vain. Through millions of years of revolution, living organisms have evolved hierarchical and anisotropic structures to maximize their survival in complex and dynamic environments. Many of these structures are intrinsically heterogeneous and often with functional gradient distributions. Understanding the convergent and divergent gradient designs in the natural material systems may lead to a new paradigm shift in the development of next-generation high-performance bio-/nano-materials and devices that are critically needed in energy, environmental remediation, and biomedical fields. Herein, we review the basic design principles and highlight some of the prominent examples of gradient biological materials/structures discovered over the past few decades. Interestingly, despite the anisotropic features in one direction (i.e., in terms of gradient compositions and properties), these natural structures retain certain levels of symmetry, including point symmetry, axial symmetry, mirror symmetry, and 3D symmetry. We further demonstrate the state-of-the-art fabrication techniques and procedures in making the biomimetic counterparts. Some prototypes showcase optimized properties surpassing those seen in the biological model systems. Finally, we summarize the latest applications of these synthetic functional gradient materials and structures in robotics, biomedical, energy, and environmental fields, along with their future perspectives. This review may stimulate scientists, engineers, and inventors to explore this emerging and disruptive research methodology and endeavors. 

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2. Internal models in control, bioengineering, and neuroscience

   Bin.M. ; Huang, J. ; Isidori, A. ; Marconi, L. ; Mischiati, M. ; E. D. Sontag, E.D. ( October 2021 , Annual review of control robotics and autonomous systems)

   Cells respond to biochemical and physical internal as well as external signals. These signals can be broadly classified into two categories: (a) ``actionable'' or ``reference'' inputs that should elicit appropriate biological or physical responses such as gene expression or motility, and (b) ``disturbances'' or ``perturbations'' that should be ignored or actively filtered-out. These disturbances might be exogenous, such as binding of nonspecific ligands, or endogenous, such as variations in enzyme concentrations or gene copy numbers. In this context, the term robustness describes the capability to produce appropriate responses to reference inputs while at the same time being insensitive to disturbances. These two objectives often conflict with each other and require delicate design trade-offs. Indeed, natural biological systems use complicated and still poorly understood control strategies in order to finely balance the goals of responsiveness and robustness. A better understanding of such natural strategies remains an important scientific goal in itself and will play a role in the construction of synthetic circuits for therapeutic and biosensing applications. A prototype problem in robustly responding to inputs is that of ``robust tracking'', defined by the requirement that some designated internal quantity (for example, the level of expression of a reporter protein) should faithfully follow an input signal while being insensitive to an appropriate class of perturbations. Control theory predicts that a certain type of motif, called integral feedback, will help achieve this goal, and this motif is, in fact, a necessary feature of any system that exhibits robust tracking. Indeed, integral feedback has always been a key component of electrical and mechanical control systems, at least since the 18th century when James Watt employed the centrifugal governor to regulate steam engines. Motivated by this knowledge, biological engineers have proposed various designs for biomolecular integral feedback control mechanisms. However, practical and quantitatively predictable implementations have proved challenging, in part due to the difficulty in obtaining accurate models of transcription, translation, and resource competition in living cells, and the stochasticity inherent in cellular reactions. These challenges prevent first-principles rational design and parameter optimization. In this work, we exploit the versatility of an Escherichia coli cell-free transcription-translation (TXTL) to accurately design, model and then build, a synthetic biomolecular integral controller that precisely controls the expression of a target gene. To our knowledge, this is the first design of a functioning gene network that achieves the goal of making gene expression track an externally imposed reference level, achieves this goal even in the presence of disturbances, and whose performance quantitatively agrees with mathematical predictions. 

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3. Quantitative characterization of 3D bioprinted structural elements under cell generated forces

   https://doi.org/10.1038/s41467-019-10919-1  

   Morley, Cameron D. ; Ellison, S. Tori ; Bhattacharjee, Tapomoy ; O’Bryan, Christopher S. ; Zhang, Yifan ; Smith, Kourtney F. ; Kabb, Christopher P. ; Sebastian, Mathew ; Moore, Ginger L. ; Schulze, Kyle D. ; et al ( July 2019 , Nature Communications)

   With improving biofabrication technology, 3D bioprinted constructs increasingly resemble real tissues. However, the fundamental principles describing how cell-generated forces within these constructs drive deformations, mechanical instabilities, and structural failures have not been established, even for basic biofabricated building blocks. Here we investigate mechanical behaviours of 3D printed microbeams made from living cells and extracellular matrix, bioprinting these simple structural elements into a 3D culture medium made from packed microgels, creating a mechanically controlled environment that allows the beams to evolve under cell-generated forces. By varying the properties of the beams and the surrounding microgel medium, we explore the mechanical behaviours exhibited by these structures. We observe buckling, axial contraction, failure, and total static stability, and we develop mechanical models of cell-ECM microbeam mechanics. We envision these models and their generalizations to other fundamental 3D shapes to facilitate the predictable design of biofabricated structures using simple building blocks in the future.

    

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4. Digital synthesis of free-form multimaterial structures for realization of arbitrary programmed mechanical responses

   https://doi.org/10.1073/pnas.2120563119  

   Li, Weichen ; Wang, Fengwen ; Sigmund, Ole ; Zhang, Xiaojia Shelly ( March 2022 , Proceedings of the National Academy of Sciences)

   Programming structures to realize any prescribed mechanical response under large deformation is highly desired for various functionalities, such as actuation and energy trapping. Yet, the use of a single material phase and heuristically developed structural patterns leads to restricted design space and potential failure to achieve specific target behaviors. Here, through a free-form inverse design approach, multiple hyperelastic materials with distinct properties are optimally synthesized into composite structures to precisely achieve arbitrary and extreme prescribed responses under large deformations. The digitally synthesized structures exhibit organic shapes and motions with irregular distributions of material phases. Within the structures, different materials play distinct roles yet seamlessly collaborate through sophisticated deformation mechanisms to produce the target behaviors, some of which are unachievable by a single material. While complex in geometry and material heterogeneity, the discovered structures are effectively manufactured via multimaterial fabrication with different polydimethylsiloxane (PDMS) elastomers with distinct behaviors and their highly nonlinear responses are physically and accurately realized in experiments. To enhance programmability, the synthesized structures are heteroassembled into architectures that exhibit highly complex yet navigable responses. The proposed synthesis, multimaterial fabrication, and heteroassembly strategy can be utilized to design function-oriented and situation-specific mechanical devices for a wide range of applications. 

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5. Materials for Implantable Surface Electrode Arrays: Current Status and Future Directions

   https://doi.org/10.1002/adma.202107207  

   Tringides, Christina M. ; Mooney, David J. ( March 2022 , Advanced Materials)

   Surface electrode arrays are mainly fabricated from rigid or elastic materials, and precisely manipulated ductile metal films, which offer limited stretchability. However, the living tissues to which they are applied are nonlinear viscoelastic materials, which can undergo significant mechanical deformation in dynamic biological environments. Further, the same arrays and compositions are often repurposed for vastly different tissues rather than optimizing the materials and mechanical properties of the implant for the target application. By first characterizing the desired biological environment, and then designing a technology for a particular organ, surface electrode arrays may be more conformable, and offer better interfaces to tissues while causing less damage. Here, the various materials used in each component of a surface electrode array are first reviewed, and then electrically active implants in three specific biological systems, the nervous system, the muscular system, and skin, are described. Finally, the fabrication of next‐generation surface arrays that overcome current limitations is discussed.

    

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