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1. Biocompatible micro tweezers for 3D hydrogel organoid array mechanical characterization

   https://doi.org/10.1371/journal.pone.0262950  

   Alhudaithy, Soliman ; Hoshino, Kazunori ( January 2022 , PLOS ONE)

   Jabbari, Esmaiel (Ed.)

   This study presents novel biocompatible Polydimethylsiloxane (PDMS)-based micromechanical tweezers (μTweezers) capable of the stiffness characterization and manipulation of hydrogel-based organoids. The system showed great potential for complementing established mechanical characterization methods such as Atomic Force Microscopy (AFM), parallel plate compression (PPC), and nanoindentation, while significantly reducing the volume of valuable hydrogels used for testing. We achieved a volume reduction of ~0.22 μl/sample using the μTweezers vs. ~157 μl/sample using the PPC, while targeting high-throughput measurement of widely adopted micro-mesoscale (a few hundred μm-1500 μm) 3D cell cultures. The μTweezers applied and measured nano-millinewton forces through cantilever’ deflection with high linearity and tunability for different applications; the assembly is compatible with typical inverted optical microscopes and fit on standard tissue culture Petri dishes, allowing mechanical compression characterization of arrayed 3D hydrogel-based organoids in a high throughput manner. The average achievable output per group was 40 tests per hour, where 20 organoids and 20 reference images in one 35 mm petri dish were tested, illustrating efficient productivity to match the increasing demand on 3D organoids’ applications. The changes in stiffness of collagen I hydrogel organoids in four conditions were measured, with ovarian cancer cells (SKOV3) or without (control). The Young’s modulus of the control group (Control—day 0, E = 407± 146, n = 4) measured by PPC was used as a reference modulus, where the relative elastic compressive modulus of the other groups based on the stiffness measurements was also calculated (control-day 0, E = 407 Pa), (SKOV3-day 0, E = 318 Pa), (control-day 5, E = 528 Pa), and (SKOV3-day 5, E = 376 Pa). The SKOV3-embedded hydrogel-based organoids had more shrinkage and lowered moduli on day 0 and day 5 than controls, consistently, while SKOV3 embedded organoids increased in stiffness in a similar trend to the collagen I control from day 0 to day 5. The proposed method can contribute to the biomedical, biochemical, and regenerative engineering fields, where bulk mechanical characterization is of interest. The μTweezers will also provide attractive design and application concepts to soft membrane-micro 3D robotics, sensors, and actuators. 

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2. Wireless sensors for continuous, multimodal measurements at the skin interface with lower limb prostheses

   https://doi.org/10.1126/scitranslmed.abc4327  

   Kwak, Jean Won ; Han, Mengdi ; Xie, Zhaoqian ; Chung, Ha Uk ; Lee, Jong Yoon ; Avila, Raudel ; Yohay, Jessica ; Chen, Xuexian ; Liang, Cunman ; Patel, Manish ; et al ( December 2020 , Science Translational Medicine)

   Precise form-fitting of prosthetic sockets is important for the comfort and well-being of persons with limb amputations. Capabilities for continuous monitoring of pressure and temperature at the skin-prosthesis interface can be valuable in the fitting process and in monitoring for the development of dangerous regions of increased pressure and temperature as limb volume changes during daily activities. Conventional pressure transducers and temperature sensors cannot provide comfortable, irritation-free measurements because of their relatively rigid construction and requirements for wired interfaces to external data acquisition hardware. Here, we introduce a millimeter-scale pressure sensor that adopts a soft, three-dimensional design that integrates into a thin, flexible battery-free, wireless platform with a built-in temperature sensor to allow operation in a noninvasive, imperceptible fashion directly at the skin-prosthesis interface. The sensor system mounts on the surface of the skin of the residual limb, in single or multiple locations of interest. A wireless reader module attached to the outside of the prosthetic socket wirelessly provides power to the sensor and wirelessly receives data from it, for continuous long-range transmission to a standard consumer electronic device such as a smartphone or tablet computer. Characterization of both the sensor and the system, together with theoretical analysis of the key responses, illustrates linear, accurate responses and the ability to address the entire range of relevant pressures and to capture skin temperature accurately, both in a continuous mode. Clinical application in two prosthesis users demonstrates the functionality and feasibility of this soft, wireless system.

    

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3. Integration of Graphene Electrodes with 3D Skeletal Muscle Tissue Models

   https://doi.org/10.1002/adhm.201901137  

   Kim, Yongdeok ; Pagan‐Diaz, Gelson ; Gapinske, Lauren ; Kim, Yerim ; Suh, Judy ; Solomon, Emilia ; Harris, Jennifer Foster ; Nam, SungWoo ; Bashir, Rashid ( January 2020 , Advanced Healthcare Materials)

   Integration of conductive electrodes with 3D tissue models can have great potential for applications in bioelectronics, drug screening, and implantable devices. As conventional electrodes cannot be easily integrated on 3D, polymeric, and biocompatible substrates, alternatives are highly desirable. Graphene offers significant advantages over conventional electrodes due to its mechanical flexibility and robustness, biocompatibility, and electrical properties. However, the transfer of chemical vapor deposition graphene onto millimeter scale 3D structures is challenging using conventional wet graphene transfer methods with a rigid poly (methyl methacrylate) (PMMA) supportive layer. Here, a biocompatible 3D graphene transfer method onto 3D printed structure using a soft poly ethylene glycol diacrylate (PEGDA) supportive layer to integrate the graphene layer with a 3D engineered ring of skeletal muscle tissue is reported. The use of softer PEGDA supportive layer, with a 10⁵times lower Young's modulus compared to PMMA, results in conformal integration of the graphene with 3D printed pillars and allows electrical stimulation and actuation of the muscle ring with various applied voltages and frequencies. The graphene integration method can be applied to many 3D tissue models and be used as a platform for electrical interfaces to 3D biological tissue system.

    

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4. 3D Printing of a Biocompatible Double Network Elastomer with Digital Control of Mechanical Properties

   https://doi.org/10.1002/adfm.201910391  

   Wang, Pengrui ; Berry, David B. ; Song, Zhaoqiang ; Kiratitanaporn, Wisarut ; Schimelman, Jacob ; Moran, Amy ; He, Frank ; Xi, Brian ; Cai, Shengqiang ; Chen, Shaochen ( February 2020 , Advanced Functional Materials)

   The majority of 3D‐printed biodegradable biomaterials are brittle, limiting their application to compliant tissues. Poly(glycerol sebacate) acrylate (PGSA) is a synthetic biocompatible elastomer and compatible with light‐based 3D printing. In this article, digital‐light‐processing (DLP)‐based 3D printing is employed to create a complex PGSA network structure. Nature‐inspired double network (DN) structures consisting of interconnected segments with different mechanical properties are printed from the same material in a single shot. Such capability has not been demonstrated by any other fabrication techniques so far. The biocompatibility of PGSA is confirmed via cell‐viability analysis. Furthermore, a finite‐element analysis (FEA) model is used to predict the failure of the DN structure under uniaxial tension. FEA confirms that the DN structure absorbs 100% more energy before rupture by using the soft segments as sacrificial elements while the hard segments retain structural integrity. Using the FEA‐informed design, a new DN structure is printed and tensile test results agree with the simulation. This article demonstrates how geometrically‐optimized material design can be easily and rapidly constructed by DLP‐based 3D printing, where well‐defined patterns of different stiffnesses can be simultaneously formed using the same elastic biomaterial, and overall mechanical properties can be specifically optimized for different biomedical applications.

    

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5. Faster Indentation Influences Skin Deformation To Reduce Tactile Discriminability of Compliant Objects

   https://doi.org/10.1109/TOH.2023.3253256  

   Li, Bingxu ; Hauser, Steven C. ; Gerling, Gregory J. ( April 2023 , IEEE Transactions on Haptics)

   To discriminate the compliance of soft objects, we rely upon spatiotemporal cues in the mechanical deformation of the skin. However, we have few direct observations of skin deformation over time, in particular how its response differs with indentation velocities and depths, and thereby helps inform our perceptual judgments. To help fill this gap, we develop a 3D stereo imaging method to observe contact of the skin’s surface with transparent, compliant stimuli. Experiments with human-subjects, in passive touch, are conducted with stimuli varying in compliance, indentation depth, velocity, and time duration. The results indicate that contact durations greater than 0.4 s are perceptually discriminable. Moreover, compliant pairs delivered at higher velocities are more difficult to discriminate because they induce smaller differences in deformation. In a detailed quantification of the skin’s surface deformation, we find that several, independent cues aid perception. In particular, the rate of change of gross contact area best correlates with discriminability, across indentation velocities and compliances. However, cues associated with skin surface curvature and bulk force are also predictive, for stimuli more and less compliant than skin, respectively. These findings and detailed measurements seek to inform the design of haptic interfaces. 

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