Tunable Stiffness Research Articles

Engineered 3D tumor microenvironment recapitulating stiffness of lung tissue to explore drug resistance of lung carcinoma

Despite clinical advances, the development of anticancer drugs faces high failure rates owing to cancer drug resistance and insufficient understanding of the native tumor microenvironment. Polymeric hydrogels are promising engineered 3D cancer models owing to their tunable properties and structural similarities to the native extracellular matrix. However, precisely mimicking the native cancer microenvironment remains challenging. In this study, we present interpenetrating polymer network (IPN) hydrogels with independent stiffness control as an engineered 3D lung carcinoma model for drug screening and basic cancer research. These IPN hydrogels are formed via horseradish peroxidase/hydrogen peroxide (H2O2)-mediated dual-crosslinking reactions, showing independently tunable stiffness at various H2O2 concentrations. Using this ability, we create engineered 3D lung cancer models that simulate normal and cancerous lung tissue stiffness with encapsulation of non-small cell lung cancer cells. We perform drug resistance tests using this system and compare the drug responses in various preclinical cancer models in vitro and in vivo. Finally, we investigate the biological mechanism underlying the acquired resistance of lung carcinoma cells to epidermal growth factor receptor inhibitors. In summary, our engineered 3D cancer model can serve as an advanced preclinical platform for drug screening and cancer biology, including the biological mechanisms of acquired drug resistance.

Preliminary exploration of the biomechanical properties of three novel cervical porous fusion cages using a finite element study

BackgroundPorous cages are considered a promising alternative to high-density cages because their interconnectivity favours bony ingrowth and appropriate stiffness tuning reduces stress shielding and the risk of cage subsidence.MethodsThis study proposes three approaches that combine macroscopic topology optimization and micropore design to establish three new types of porous cages by integrating lattices (gyroid, Schwarz, body-centred cubic) with the optimized cage frame. Using these three porous cages along with traditional high-density cages, four ACDF surgical models were developed to compare the mechanical properties of facet articular cartilage, discs, cortical bone, and cages under specific loads.ResultsThe facet joints in the porous cage groups had lower contact forces than those in the high-density cage group. The intervertebral discs in all models experienced maximum stress at the C5/6 segment. The stress distribution on the cortical bone surface was more uniform in the porous cage groups, leading to increased average stress values. The gyroid, Schwarz, and BCC cage groups showed higher average stress on the C5 cortical bone. The average stress on the surface of porous cages was higher than that on the surface of high-density cages, with the greatest difference observed under the lateral bending condition. The BCC cage demonstrated favourable mechanical stability.ConclusionThe new porous cervical cages satifies requirements of low rigidity and serve as a favourable biological scaffold for bone ingrowth. This study provides valuable insights for the development of next-generation orthopaedic medical devices.

Abstract 16997: Cardiomyocyte-Autonomous and Microtubule Dependent Mechanisms Are Sufficient to Mediate Load-Dependent T-Tubule Remodeling

Background: Mechanical overload is an established contributor to T-tubule (TT) remodeling and associated dyssynchronous Ca 2+ release leading to abnormal excitation-contraction coupling in cardiomyopathies. We examined the induction of pathological TT remodeling in isolated cardiomyocytes and the involvement of microtubules (MT) in this process. Methods: Adult rat ventricular myocytes (aRVMs) were cultured with applied variable in vitro load for 48hrs at either physiological (10kPa) or pathological (50kPa) stiffness, using custom magnetorheological elastomers with tunable stiffness. Cells were stained with Di-8-ANEPPS and Fluo-4-AM and imaged using confocal microscopy. Field stimulation of cells allowed for Ca 2+ transient acquisition via line scans. Protein expression changes were determined via Western blotting. IF staining allowed for visualization of the MT network and relevant TT proteins (TCAP, JPH2, BIN1). MT and tyrosination state dependency of remodeling was investigated by 1μM nocodazole (MT depolymerizer), taxol (MT stabilizer), and tubulin tyrosine ligase (TTL) treatments to alter the MT network accordingly. Results: Compared to the physiological stiffness group, aRVMs subjected to pathologically increased stiffness exhibited a 14.7% decrease in density, 18.9% decrease in regularity, and a 26.6% increase in luminal dimension of the TT system, along with an increase in longitudinal elements (p<0.05). The changes in both Ca 2+ handling parameters and protein expression resembled those typical of the in vivo myopathic phenotype. This included a 21.7% decrease in amplitude, along with a 33.7%, 29.8% and 21.1% increase in time to peak (TTP), variance in TTP, and the signal decay tau, respectively (p<0.05). Treatment of pathologically loaded cells with taxol worsened TT remodeling, specifically with respect to TT density which decreased by 12.5% compared to nontreatment cells, and longitudinal elements which increased by 24%. Increased MT tyrosination through TTL treatment showed a 37% recovery in TT density in cells cultured at pathological stiffness compared to nontreatment cells (p<0.05). Conclusion: The results suggest that load-induced TT remodeling occurs via a cardiomyocyte autonomous, MT-dependent mechanism.

A novel quasi-zero-stiffness isolation platform via tunable positive and negative stiffness compensation mechanism

A novel quasi-zero-stiffness isolation platform via tunable positive and negative stiffness compensation mechanism

Bioactive and chemically defined hydrogels with tunable stiffness guide cerebral organoid formation and modulate multi-omics plasticity in cerebral organoids.

Organoids are an emerging technology with great potential in human disease modelling, drug development, diagnosis, tissue engineering, and regenerative medicine. Organoids as 3D-tissue culture systems have gained special attention in the past decades due to their ability to faithfully recapitulate the complexity of organ-specific tissues. Despite considerable successes in culturing physiologically relevant organoids, their real-life applications are currently limited by challenges such as scarcity of an appropriate biomimetic matrix. Peptide amphiphiles (PAs) due to their well-defined chemistry, tunable bioactivity, and extracellular matrix (ECM)-like nanofibrous architecture represent an attractive material scaffold for organoids development. Using cerebral organoids (COs) as exemplar, we demonstrate the possibility to create bio-instructive hydrogels with tunable stiffness ranging from 0.69kPa to 2.24kPa to culture and induce COs growth. We used orthogonal chemistry involving oxidative coupling and supramolecular interactions to create two-component hydrogels integrating the bio-instructive activity and ECM-like nanofibrous architecture of a laminin-mimetic PAs (IKVAV-PA) and tunable crosslinking density of hyaluronic acid functionalized with tyramine (HA-Try). Multi-omics technology including transcriptomics, proteomics, and metabolomics reveals the induction and growth of COs in soft HA-Tyr hydrogels containing PA-IKVAV such that the COs display morphology and biomolecular signatures similar to those grown in Matrigel scaffolds. Our materials hold great promise as a safe synthetic ECM for COs induction and growth. Our approach represents a well-defined alternative to animal-derived matrices for the culture of COs and might expand the applicability of organoids in basic and clinical research. STATEMENT OF SIGNIFICANCE: Synthetic bio-instructive materials which display tissue-specific functionality and nanoscale architecture of the native extracellular matrix are attractive matrices for organoids development. These synthetic matrices are chemically defined and animal-free compared to current gold standard matrices such as Matrigel. Here, we developed hydrogel matrices with tunable stiffness, which incorporate laminin-mimetic peptide amphiphiles to grow and expand cerebral organoids. Using multi-omics tools, the present study provides exciting data on the effects of neuro-inductive cues on the biomolecular profiles of brain organoids.

Modular design of curved beam-based recyclable architected materials

Advances in manufacturing technologies have enabled architected materials with unprecedented properties. These materials are typically irreversibly designed and fabricated with characteristic geometries and specific mechanical properties, thus rendering them suitable for pre-specified requests. However, these materials cannot be recycled or reconstructed into different shapes and functionalities to economically adapt to various environments. Hence, we present a modular design strategy to create a category of recyclable architected materials comprising elastic initially curved beams and rigid cylindrical magnets. Based on numerical analyses and physical prototypes, we introduce an arc-serpentine curved beam (ASCB) and systematically investigate its mechanical properties. Subsequently, we develop two sets of hierarchical modules for the ASCB, thus expanding the constructable shape of architected materials from regular cuboids to complex curved surfaces. Furthermore, we demonstrate that the magnets attached to the centers of specific serpentine patterns of the modules allows the effective in-situ recycling of the designed materials, including sheet materials for non-damage storage, bulk materials for tunable stiffness, and protective package boxes for reshaping into decorative lampshades. We expect our approach to improve the flexibility of architected materials for multifunctional implementation in resource-limited scenarios.

A magnetorheological vibration absorber with bidirectional tunability for pipelines

A magnetorheological elastomer (MRE) is employed as a tunable stiffness element in a dynamic vibration absorber (DVA) due to its remarkable magnetic tunability. However, the natural frequency of the MRE-based DVA can only be tuned towards high frequency under magnetic fields, which fails to solve, or even exacerbates, the low-frequency pipeline vibration. To tackle this issue, an innovative DVA (H-DVA) with bidirectional magnetic tunability is proposed in this paper. The hard magnetic MRE filled by NdFeB particles is selected as the core tunable stiffness element in H-DVA. Besides, the discretization distribution design scheme for the mass oscillators is adopted to improve the flexibility of H-DVA. Then, the magnetic field simulation and resonance frequency shifting test of H-DVA under different magnetic fields are completed to validate the bidirectional magnetic tunability. Lastly, the vibration absorption effect is verified in a self-established experimental pipeline system. The experiment results demonstrate that the resonance frequency of the proposed H-DVA exhibites a maximum frequency shift of approximately −2.7 Hz under reversed magnetic field. Compared to H-DVA working in zero field state, the acceleration magnitude of the pipeline vibration is further reduced by 8.8% when applying −1.5 A to the H-DVA under 55 Hz excitation. Similarly, the acceleration magnitude is further reduced by 22.2% when applying 2 A to the H-DVA under 85 Hz excitation. Thus, these findings confirm that the H-DVA proposed in this paper not only achieves the bidirectional magnetic tunability, but also improves the vibration absorption effect for pipeline vibration.

A Dual-Modal Hybrid Gripper with Wide Tunable Contact Stiffness Range and High Compliance for Adaptive and Wide-Range Grasping Objects with Diverse Fragilities.

The difficulties of traditional rigid/soft grippers in meeting the increasing performance expectations (e.g., high grasping adaptability and wide graspable objects range) of a single robotic gripper have given birth to numerous soft-rigid coupling grippers with promising performance. However, it is still hard for these hybrid grippers to adaptively grasp various objects with diverse fragilities intact, such as incense ash and orange, due to their limited contact stiffness adjustable range and compliance. To solve these challenging issues, herein, we propose a dual-modal hybrid gripper, whose fingers contain a detachable elastomer-coated flexible sheet that is restrained by a moving frame as a teardrop shape. The gripper's two modes switched by controlling the moving frame position can selectively highlight the low contact stiffness and excellent compliance of the teardrop-shaped flexible sheets and the high contact stiffness of the moving frames. Moreover, the contact stiffness of the teardrop-shaped sheets can be wide-range adjusted by online controlling the moving frame position and offline replacing the sheets with different thicknesses. The compliance of the teardrop-shaped sheets also proves to be excellent compared with an Ecoflex 10 fingertip with the same profile. Such a gripper with wide-range tunable contact stiffness and high compliance demonstrates excellent grasping adaptability (e.g., it can safely grasp several fragile strawberries with a maximum size difference of 18 mm, a strawberry with a left/right offset of 3 cm, and a strawberry in two different lying poses) and wide-range graspable objects (from 0.1 g super fragile cigarette ashes to 5.1 kg dumbbell).

A method for classifying snow using ski-mounted strain sensors

Qualitative characteristics of snow can vary substantially from day to day as well as across aspects and elevations. This makes it challenging for skiers to choose the right ski, and for ski manufacturers to design and evaluate their ski's performance across diverse real-world conditions. Here, we explore a proof-of-concept approach for automatically assessing qualitative aspects of snow type while skiing using strain sensors mounted to the top surface of an alpine ski. We show that with two strain gauges and an inertial measurement unit it is feasible to correctly assign one of three qualitative labels (powder, slushy, or icy/groomed snow) to each 10 s segment of a trajectory. Our dataset included two general skiing styles—wide turns and tight turns—and for our data the algorithm we developed was able to correctly assign the qualitative labels with 97% accuracy. Our algorithm uses a combination of a data-driven linear model of the ski-snow interaction, dimensionality reduction, and a Naïve Bayes classifier. Comparisons of classifier performance between strain gauges suggest that the optimal placement of strain gauges is halfway between the binding and the tip/tail of the ski, in the cambered section just before the point where the unweighted ski would touch the snow surface. A key component of our approach is to use the relative dynamics between the inertial measurement unit under the boot and the strain gauges placed farther away, making it possible the distinguish dynamics that are a result of the snow rather than the skiers input. The ability to classify snow, potentially in real-time, using skis opens the door to applications including improved quantitative characterization of ski performance across a range of conditions, snow specific recommendations for ski selection and technique coaching, and future development of skis with automated stiffness tuning based on the snow type.

3D Bioprintable Hydrogel with Tunable Stiffness for Exploring Cells Encapsulated in Matrices of Differing Stiffnesses.

In vitro cell models have undergone a shift from 2D models on glass slides to 3D models that better reflect the native 3D microenvironment. 3D bioprinting promises to progress the field by allowing the high-throughput production of reproducible cell-laden structures with high fidelity. The current stiffness range of printable matrices surrounding the cells that mimic the extracellular matrix environment remains limited. The work presented herein aims to expand the range of stiffnesses by utilizing a four-armed polyethylene glycol with maleimide-functionalized arms. The complementary cross-linkers comprised a matrix metalloprotease-degradable peptide and a four-armed thiolated polymer which were adjusted in ratio to tune the stiffness. The modularity of this system allows for a simple method of controlling stiffness and the addition of biological motifs. The application of this system in drop-on-demand printing is validated using MCF-7 cells, which were monitored for viability and proliferation. This study shows the potential of this system for the high-throughput investigation of the effects of stiffness and biological motif compositions in relation to cell behaviors.

Characteristic analysis of a novel magnetorheological fabric composite cored flexible sandwich beam with tunable stiffness

This paper focuses on the performance improvement and evaluation of a novel flexible sandwich beam incorporated magnetorheological fluid porous fabric (MRF-PF). As a novel MR material, MRF-PF has been introduced, prepared, and measured to analyze the pre-yield property between complex shear modulus and magnetic fields. MRF-PF is used into the flexible sandwich beam as core layer. Pre-yield property with tunable stiffness is used to adjust the dynamic response. Then, a theoretical model is derived which can precisely describe the performance. Based on experimental results, sandwich beam incorporated MRF-PF has a good performance of controllability. When the magnetic field is applied into the free end, the natural frequency decreases with increasing the currents and filling ratio. In contrast, the frequency and amplitude increase when the clamped end is exposed to the magnetic fields. Comparing with other investigations, this proposed sandwich beam incorporated MRF-PF has a larger frequency range. The first and second natural frequency show the increases of 54.8% and 77.2%, respectively. The reduction of amplitude is closely related to the thickness of face plate. Therefore, the performance of the compound sandwich beam can be significantly improved by MRF-PF.

Semi-Physical Modeling of Soft Pneumatic Actuators With Stiffness Tuning

Abstract The inherent low stiffness in soft robots makes them preferable for working in close proximity to humans. However, having this low stiffness creates challenges when operating in terms of control and sensitivity to disturbances. To alleviate this issue, soft robots often have built-in stiffness tuning mechanisms that allow for controlled increases in stiffness. Additionally, redundant pneumatic manipulators can utilize antagonistic pressure to achieve identical positions under increased stiffness. In this paper, we develop a model to predict the stiffness and configuration of a pneumatic soft manipulator under different pressure inputs and external forces. The model is developed based on the physical characteristics of a soft manipulator while enabling efficient parameter estimation and computation. The efficacy of the modeling approach is supported via experimental results.

Autonomous Adaption of Intelligent Humidity‐Programmed Hydrogel Patches for Tunable Stiffness and Drug Release (Adv. Mater. Technol. 19/2023)

Autonomous Adaption of Intelligent Humidity‐Programmed Hydrogel Patches for Tunable Stiffness and Drug Release (Adv. Mater. Technol. 19/2023)

An adaptive and space-energy efficiency vibration absorber system using a self-sensing and tunable magnetorheological elastomer

Vibration monitoring and buffering is an important technical task in many industrial fields, such as bridges, machine tools and other specific applications. Recently, a magneto-rheological elastomer (MRE) has been utilized in an intelligent vibration absorber system with tunable stiffness, which can reversibly regulate its resonant frequency in real time to effectively prevent the resonance of the mechanical system. However, this MRE must be integrated with a vibrational sensor and equipped with an external magnetic field (e.g., electromagnetic coils or permanent magnets). Thus, the overall system is usually bulky and energy-intensive, which severely limits its broad application potential. In this work, we present an MRE-based tunable vibration absorber (MRE-TVA) with an elaborate 3-layered architecture integrated with a self-sensing triboelectric nanogenerator (TENG) sensor. The inner two-layer MRE structure exhibits variable stiffness, while the outer layer of the negative Poisson's ratio structure can confine the deformation of the inner MRE layers and form a contact-separation TENG sensor with the MRE, where the sensor can recognize external vibration information in a timely manner. In particular, the TENG sensor enables sensitive identification of the abnormal state of resonant excitation and other mechanical disturbances through dual logic judgment control based on vibration frequency and amplitude. For energy-space efficiency, a bistable permanent magnet controlled by a pulse current is integrated to generate a desirable magnetic field for modulation of the MRE stiffness. Compared with traditional electromagnetic coils, the energy and space utilization rates are increased by 94.25% and 75%, respectively. This combination of self-sensing and vibration damping systems achieves high energy-space efficiency, which will enable the intelligent health monitoring of bridges and other autonomous, smart, and long-term engineering tasks.

Fabrication of versatile polyvinyl alcohol and carboxymethyl cellulose-based hydrogels for information hiding and flexible sensors: Heat-induced adjustable stiffness and transparency

With the growing demand for wearable electronics, designing biocompatible hydrogels that combine self-repairability, wide operating temperature and precise sensing ability offers a promising scheme. Herein, by interpenetrating naturally derived carboxymethyl cellulose (CMC) into a polyvinyl alcohol (PVA) gel matrix, a novel hydrogel is successfully developed via simple coordination with calcium chloride (CaCl2). The chelation of CMC and Ca2+ is applied as a second crosslinking mechanism to stabilize the hydrogel at relatively high temperature (95 °C). In particular, it has unique heat-induced healing behavior and unexpected tunable stiffness & transparency. Like the sea cucumber, the gel can transform between a stiffened state and a relaxed state (nearly 23 times modulated stiffness from 453 to 20 kPa) which originates from the reconstruction of the crystallites. The adjustable transparency enables the hydrogel to become an excellent information hiding material. Due to the presence of Ca2+, the hydrogels show favorable conductivity, anti-freezing and long-term stability. Based on the advantages, a self-powered sensor, where chemical energy is converted to electrical energy, is assembled for human motion detection. The low-cost, environmentally friendly strategy, at the same time, complies to the “green” chemistry concept with the full employment of the biopolymers. Therefore, the proposed hydrogel is deemed to find potential use in wearable sensors.

3D Printing of Ti-6Al-4V-Based Porous-Channel Dental Implants: Computational, Biomechanical, and Cytocompatibility Analyses.

Objective: Loosening of dental implants due to resorption of the surrounding bone is one of the challenging clinical complications in prosthetic dentistry. Generally, stiffness mismatch between an implant and its surrounding bone is one of the major factors. In order to prevent such clinical consequences, it is essential to develop implants with customized stiffness. The present study investigates the computational and experimental biomechanical responses together with cytocompatibility studies of three-dimensional (3D)-printed Ti-6Al-4V-based porous dental implants with varied stiffness properties. Methods: Additive manufacturing (direct metal laser sintering, DMLS) was utilized to create Ti-6Al-4V implants having distinct porosities and pore sizes (650 and 1000 μm), along with a nonporous (solid) implant. To validate the compression testing of the constructed implants and to probe their biomechanical response, finite element models were employed. The cytocompatibility of the implants was assessed using MG-63 cells, in vitro. Results: Both X-ray microcomputed tomography (μ-CT) and scanning electron microscopy (SEM) studies illustrated the ability of DMLS to produce implants with the designed porosities. Biomechanical analysis results revealed that the porous implants had less stiffness and were suitable for providing the appropriate peri-implant bone strain. Although all of the manufactured implants demonstrated cell adhesion and proliferation, the porous implants in particular supported better bone cell growth and extracellular matrix deposition. Conclusions: 3D-printed porous implants showed tunable stiffness properties with clinical translational potential.

On a principle for mass sensing using self-excited template dynamics of coupled oscillators and root-finding algorithms

In this work, we analyze a mass sensing mechanism that relies on self-excited template dynamics of a simple network of two coupled oscillators, one linear and one nonlinear, to detect changes in the mass of the linear oscillator with tunable sensitivity. The resultant shift in the ratio of oscillation amplitudes is predicted using perturbation analysis and verified against numerical results obtained via parameter continuation. A physical realization of the mass sensing mechanism is proposed, in which the linear oscillator is represented by a periodically excited actuator/microcantilever assembly, the nonlinear oscillator is simulated in silico on a finite interval of time while driven by the periodic steady-state response of the linear oscillator, and a nonlinear root-finding algorithm is used to identify the input to the actuator that reproduces the sought, coupled, self-excited dynamics. The analysis shows that the sensor gain can be adjusted by appropriate tuning of the coupling stiffness without modifications to the physical components. Numerical results for two different actuator models demonstrate rapid convergence of the root-finding algorithm from a trivial initial solution guess over ranges of values of model parameters and added mass ratios.

Microstructurally and mechanically tunable acellular hydrogel scaffold using carboxymethyl cellulose for potential osteochondral tissue engineering

In tissue engineering, scaffold microstructures and mechanical cues play a significant role in regulating stem cell differentiation, proliferation, and infiltration, offering a promising strategy for osteochondral tissue repair. In this present study, we aimed to develop a facile method to fabricate an acellular hydrogel scaffold (AHS) with tunable mechanical stiffness and microstructures using carboxymethyl cellulose (CMC). The impacts of the degree of crosslinking, crosslinker length, and matrix density on the AHS were investigated using different characterization methods, and the in vitro biocompatible of AHS was also examined. Our CMC-based AHS showed tunable mechanical stiffness ranging from 50 kPa to 300 kPa and adjustable microporous size between 50 μm and 200 μm. In addition, the AHS was also proven biocompatible and did not negatively affect rabbit bone marrow stem cells' dual-linage differentiation into osteoblasts and chondrocytes. In conclusion, our approach may present a promising method in osteochondral tissue engineering.

Tunable Stiffness Caudal Peduncle Leads to Higher Swimming Speed Without Extra Energy

Tunable Stiffness Caudal Peduncle Leads to Higher Swimming Speed Without Extra Energy

Impedance tracking control of magnetostrictive transducer based on variable stiffness tuning

Impedance tracking control of magnetostrictive transducer based on variable stiffness tuning