A Versatile 3D-Printable Soft Pneumatic Actuator Design for Multi-Functional Applications in Soft Robotics.

Soft pneumatic actuators (SPAs) play a crucial role in generating movements and forces in soft robotic systems. However, existing SPA designs require significant structural modifications to be used in applications other than their original design. The present article proposes an omni-purpose fully 3D-printable SPA design inspired by membrane type mold and cast SPAs. The design features a spring-like zig-zag structure 3D-printed using an affordable 3D printer with thermoplastic polyurethane and a minimum wall thickness between 0.4 and 0.6 mm. The new SPA can perform unidirectional extension (30% extension) and bidirectional (rotation around same axis) bending (100°), with the ability to exert 10 N blocking force for 350 kPa pressure input. In addition, the design exhibits the capability to be scaled down for the purpose of accommodating limited spaces, while simultaneously enabling the reconfigurable interconnection of multiple SPAs to adapt to larger areas and navigate intricate trajectories that were not originally intended. The SPA's ability to be used in multiple applications without structural modification was validated through testing as a robot end-effector (gripper), artificial muscles in a soft tendon-driven prosthetic hand, a tube/tunnel navigator, and a robot crawler.

A Fusion Algorithm Based on a Constant Velocity Model for Improving the Measurement of Saccade Parameters with Electrooculography.

Electrooculography (EOG) serves as a widely employed technique for tracking saccadic eye movements in a diverse array of applications. These encompass the identification of various medical conditions and the development of interfaces facilitating human-computer interaction. Nonetheless, EOG signals are often met with skepticism due to the presence of multiple sources of noise interference. These sources include electroencephalography, electromyography linked to facial and extraocular muscle activity, electrical noise, signal artifacts, skin-electrode drifts, impedance fluctuations over time, and a host of associated challenges. Traditional methods of addressing these issues, such as bandpass filtering, have been frequently utilized to overcome these challenges but have the associated drawback of altering the inherent characteristics of EOG signals, encompassing their shape, magnitude, peak velocity, and duration, all of which are pivotal parameters in research studies. In prior work, several model-based adaptive denoising strategies have been introduced, incorporating mechanical and electrical model-based state estimators. However, these approaches are really complex and rely on brain and neural control models that have difficulty processing EOG signals in real time. In this present investigation, we introduce a real-time denoising method grounded in a constant velocity model, adopting a physics-based model-oriented approach. This approach is underpinned by the assumption that there exists a consistent rate of change in the cornea-retinal potential during saccadic movements. Empirical findings reveal that this approach remarkably preserves EOG saccade signals, resulting in a substantial enhancement of up to 29% in signal preservation during the denoising process when compared to alternative techniques, such as bandpass filters, constant acceleration models, and model-based fusion methods.

Quantifying the Impact of Cancer on the Viscoelastic Properties of the Prostate Gland using a Quasi-Linear Viscoelastic Model.

Pathological disorders can alter the mechanical properties of biological tissues, and studying such changes can help to better understand the disease progression. The prostate gland is no exception, as previous studies have shown that cancer can affect its mechanical properties. However, most of these studies have focused on the elastic properties of the tissue and have overlooked the impact of cancer on its viscous response. To address this gap, we used a quasi-linear viscoelastic model to investigate the impact of cancer on both the elastic and viscous characteristics of the prostate gland. By comparing the viscoelastic properties of segments influenced by cancer and those unaffected by cancer in 49 fresh prostates, removed within two hours after prostatectomy surgery, we were able to determine the influence of cancer grade and tumor volume on the tissue. Our findings suggest that tumor volume significantly affects both the elastic modulus and viscosity of the prostate (p-value less than 2%). Specifically, we showed that cancer increases Young's modulus and shear relaxation modulus by 20%. These results have implications for using mechanical properties of the prostate as a potential biomarker for cancer. However, developing an in vivo apparatus to measure these properties remains a challenge that needs to be addressed in future research. STATEMENT OF SIGNIFICANCE: This study is the first to explore how cancer impacts the mechanical properties of prostate tissues using a quasi-linear viscoelastic model. We examined 49 fresh prostate samples collected immediately after surgery and correlated their properties with cancer presence identified in pathology reports. Our results demonstrate a 20% change in the viscoelastic properties of the prostate due to cancer. We initially validated our approach using tissue-mimicking phantoms and then applied it to differentiate between cancerous and normal prostate tissues. These findings offer potential for early cancer detection by assessing these properties. However, conducting these tests in vivo remains a challenge for future research.

Mechanisms of Pathogenicity of Hypertrophic Cardiomyopathy-Associated Troponin T (TNNT2) Variant R278C+/- During Development.

Hypertrophic cardiomyopathy (HCM) is one of the most common heritable cardiovascular diseases and variants of TNNT2 (cardiac troponin T) are linked to increased risk of sudden cardiac arrest despite causing limited hypertrophy. In this study, a TNNT2 variant, R278C+/-, was generated in both human cardiac recombinant/reconstituted thin filaments (hcRTF) and human- induced pluripotent stem cells (hiPSCs) to investigate the mechanisms by which the R278C+/- variant affects cardiomyocytes at the proteomic and functional levels. The results of proteomics analysis showed a significant upregulation of markers of cardiac hypertrophy and remodeling in R278C+/- vs. the isogenic control. Functional measurements showed that R278C+/- variant enhances the myofilament sensitivity to Ca2+, increases the kinetics of contraction, and causes arrhythmia at frequencies >75 bpm. This study uniquely shows the profound impact of the TNNT2 R278C+/- variant on the cardiomyocyte proteomic profile, cardiac electrical and contractile function in the early stages of cardiac development.

Controlled and localized antibiotics delivery using magnetic-responsive beads for synergistic treatment of orthopedic infection.

Antibiotic-loaded bone cement beads have been a reliable passive delivery system for the localized treatment of osteomyelitis; however, low, and unregulated drug release rates limit the ability of this system to maintain therapeutic concentrations. This problem is further amplified by drug-resistant pathogens that might invade or evolve under these conditions. Furthermore, currently available bone cements are incompatible with some antibiotics. The proposed device resembles conventional bone cement beads but contains an on-demand drug delivery magnetic sponge that provides actively controlled release of antibiotics. The slightly porous structure facilitates some drug diffusion while further drug release may be controlled remotely via magnetic actuation. Additionally, a combination of silver nitrate and gentamicin are used in the device as these agents are shown to display a synergistic antibacterial activity in vitro using checkerboard and time-kill assays. The device releases gentamicin and silver in both actuation and diffusion modes over 7 days. The in vitro bacterial studies demonstrate the efficacy of the released agents alone, and synergistically in combination, against Methicillin-resistant Staphylococcus aureus and Escherichia coli. The proposed device offers a facile fabrication process which allows control of the release profile by engineering hole configurations or manipulating magnetic field strength to provide the most effective therapy.

The Use of Surface-Modified Nanocrystalline Cellulose Integrated Membranes to Remove Drugs from Waste Water and as Polymers to Clean Oil Sands Tailings Ponds.

There is an urgent environmental need to remediate waste water. In this study, the use of surface-modified nanocrystalline cellulose (CNC) to remove polluting drugs or chemicals from waste water and oil sands tailing ponds has been investigated. CNC was modified by either surface adsorbing cationic or hydrophobic species or by covalent methods and integrated into membrane water filters. The removal of either diclofenac or estradiol from water was studied. Similar non-covalently modified CNC materials were used to flocculate clays from water or to bind naphthenic acids which are contaminants in tailing ponds. Estradiol bound well to hydrophobically modified CNC membrane filter systems. Similarly, diclofenac (anionic drug) bound well to covalently cationically modified CNC membranes. Non-covalent modified CNC effectively flocculated clay particles in water and bound two naphthenic acid chemicals (negatively charged and hydrophobic). Modified CNC integrated into water filter membranes may remove drugs from waste or drinking water and contaminants from tailing ponds water. Furthermore, the ability of modified CNC to flocculate clays particles and bind naphthenic acids may allow for the addition of modified CNC directly to tailing ponds to remove both contaminants. CNC offers an environmentally friendly, easily transportable and disposable novel material for water remediation purposes.

Quasi-Linear Viscoelastic Characterization of Soft Tissue-Mimicking Materials.

We present a novel method based on the quasi-linear viscoelastic (QLV) theory to describe the time-dependent behavior of soft materials. Unlike previous methods for deriving QLV parameters, we characterize the elastic and viscous behavior of materials separately by using two different sets of experiments. To model the nonlinear elastic behavior, we fit the elastic stress response with a one-term Ogden model. Then, we model the relaxation behavior with a Prony series to compare the stress relaxation of the material at different timescales. This new method allows us to characterize materials with narrow confidence intervals (high accuracy), independently from the loading conditions. We validate our model using samples made of phantom materials that mimic normal and cancerous prostate tissues in terms of Young's modulus. Our model is shown to distinguish materials with similar elastic (viscous) properties but different viscous (elastic) properties. Drawing a precise distinction between the phantoms, this method could be useful for prostate cancer (PCa) diagnosis; but significant clinical studies will be needed in the future.

Antibacterial hydrogel coating: Strategies in surface chemistry.

Hydrogels have emerged as promising antimicrobial materials due to their unique three-dimensional structure, which provides sufficient capacity to accommodate various materials, including small molecules, polymers and particles. Coating substrates with antibacterial hydrogel layers has been recognized as an effective strategy to combat bacterial colonization. To prevent possible delamination of hydrogel coatings from substrates, it is crucial to attach hydrogel layers via stronger links, such as covalent bonds. To date, various surface chemical strategies have been developed to introduce hydrogel coatings on different substrates. In this review, we first give a brief introduction of the major strategies for designing antibacterial coatings. Then, we summarize the chemical methods used to fix the antibacterial hydrogel layer on the substrate, which include surface-initiated graft crosslinking polymerization, anchoring the hydrogel layer on the surface during crosslinking, and chemical crosslinking of layer-by-layer coating. The reaction mechanisms of each method and matched pretreatment strategies are systemically documented with the aim of introducing available protocols to researchers in related fields for designing hydrogel-coated antibacterial surfaces.

Co-culture of induced pluripotent stem cells with cardiomyocytes is sufficient to promote their differentiation into cardiomyocytes.

Various types of stem cells and non-stem cells have been shown to differentiate or transdifferentiate into cardiomyocytes by way of co-culture with appropriate inducer cells. However, there is a limited demonstration of a co-culture induction system utilizing stem cell-derived cardiomyocytes as a stimulatory source for cardiac reprogramming (of stem cells or otherwise). In this study, we utilized an inductive co-culture method to show that previously differentiated induced pluripotent stem (iPS) cell-derived cardiomyocytes (iCMs), when co-cultivated with iPS cells, constituted a sufficient stimulatory system to induce cardiac differentiation. To enable tracking of both cell populations, we utilized GFP-labeled iPS cells and non-labeled iCMs pre-differentiated using inhibitors of GSK and Wnt signaling. Successful differentiation was assessed by the exhibition of spontaneous self-contractions, structural organization of α-actinin labeled sarcomeres, and expression of cardiac specific markers cTnT and α-actinin. We found that iCM-iPS cell-cell contact was essential for inductive differentiation, and this required overlaying already adherent iPS cells with iCMs. Importantly, this process was achieved without the exogenous addition of pathway inhibitors and morphogens, suggesting that 'older' iCMs serve as an adequate stimulatory source capable of recapitulating the necessary culture environment for cardiac differentiation.

Design and Near-Infrared Actuation of a Gold Nanorod⁻Polymer Microelectromechanical Device for On-Demand Drug Delivery.

Polymeric drug delivery systems usually deliver drugs by diffusion with an initial burst of release followed by a slower prolonged release phase. An optimal system would release exact doses of drugs using an on-demand external actuation system. The purpose of this study was to design and characterize a novel drug-delivery device that utilizes near infrared (NIR 800 nm) laser-actuated drug release. The device was constructed from biocompatible polymers comprising a reservoir of drug covered by an elastic perforated diaphragm composed of a bilayer of two polymers with different thermal expansion coefficients (ethylenevinylacetate (EVA) and polydimethylsiloxane (PDMS) containing gold nanoparticles). Upon illumination with a NIR laser, the gold nanoparticles rapidly heated the bilayer resulting in bending and a drug-pumping action through the perforated bilayer, following sequential laser-actuation cycles. Devices filled with the anti-proliferative drug docetaxel were seen to release only small amounts of drug by diffusion but to release large and reproducible amounts of drug over 20 s laser-actuation periods. Because NIR 800 nm is tissue-penetrating without heating tissue, suitable geometry drug-delivery devices might be implanted in the body to be actuated by an externally applied NIR laser to allow for on-demand exact drug dosing in vivo.

Mechanically enhanced nested-network hydrogels as a coating material for biomedical devices.

Well-organized composite formations such as hierarchical nested-network (NN) structure in bone tissue and reticular connective tissue present remarkable mechanical strength and play a crucial role in achieving physical and biological functions for living organisms. Inspired by these delicate microstructures in nature, an analogous scaffold of double network hydrogel was fabricated by creating a poly(2-hydroxyethyl methacrylate) (pHEMA) network in the porous structure of alginate hydrogels. The resulting hydrogel possessed hierarchical NN structure and showed significantly improved mechanical strength but still maintained high elasticity comparable to soft tissues due to a mutual strengthening effect between the two networks. The tough hydrogel is also self-lubricated, exhibiting a surface friction coefficient comparable with polydimethylsiloxane (PDMS) substrates lubricated by a commercial aqueous lubricant (K-Y Jelly) and other low surface friction hydrogels. Additional properties of this hydrogel include high hydrophilicity, good biocompatibility, tunable cell adhesion and bacterial resistance after incorporation of silver nanoparticles. Firm bonding of the hydrogel on silicone substrates could be achieved through facile chemical modification, thus enabling the use of this hydrogel as a versatile coating material for biomedical applications. STATEMENT OF SIGNIFICANCE: In this study, we developed a tough hydrogel by crosslinking HEMA monomers in alginate hydrogels and forming a well-organized structure of hierarchical nested network (NN). Different from most reported stretchable alginate-based hydrogels, the NN hydrogel shows higher compressive strength but retains comparable softness to alginate counterparts. This work further demonstrated the good integration of the tough hydrogel with silicone substrates through chemical modification and micropillar structures. Other properties including surface friction, biocompatibility and bacterial resistance were investigated and the hydrogel shows a great promise as a versatile coating material for biomedical applications.

Magnetically-actuated drug delivery device (MADDD) for minimally invasive treatment of prostate cancer: An in vivo animal pilot study.

BACKGROUND: The vast majority of prostate cancer presents clinically localized to the prostate without evidence of metastasis. Currently, there are several modalities available to treat this particular disease. Despite radical prostatectomy demonstrating a modest prostate cancer specific mortality benefit in the PIVOT trial, several novel modalities have emerged to treat localized prostate cancer in patients that are either not eligible for surgery or that prefer an alternative approach. METHODS: Athymic nude mice were subcutaneously inoculated with prostate cancer cells. The mice were divided into four cohorts, one cohort untreated, two cohorts received docetaxel (10 mg/kg) either subcutaneously (SC) or intravenously (IV) and the fourth cohort was treated using the magnetically-actuated docetaxel delivery device (MADDD), dispensing 1.5 µg of docetaxel per 30 min treatment session. Treatment in all three therapeutic arms (SC, IV, and MADDD) was administered once weekly for 6 weeks. Treatment efficacy was measured once a week according to tumor volume using ultrasound. In addition, calipers were used to assess tumor volume. RESULTS: Animals implanted with the device demonstrated no signs of distress or discomfort, neither local nor systemic symptoms of inflammation and infection. Using an independent sample t-test, the tumor growth rate of the treated tumors was significant when compared to the control. Post hoc Tukey HSD test results showed that the mean tumor growth rate of our device cohort was significantly lower than SC and control cohorts. Moreover, IV cohort showed slight reduction in mean tumor growth rates than the ones from the device cohort, however, there was no statistical significance in tumor growth rate between these two cohorts. Furthermore, immunohistochemistry demonstrated an increased cellular apoptosis in the MADDD treated tumors and a decreased proliferation when compared to the other cohorts. In addition, IV cohort showed increased treatment side effects (weight loss) when compared to the device cohort. Finally, MADDD showed minimal expression of CD45 comparable to the control cohort, suggesting no signs of chronic inflammation. CONCLUSIONS: In conclusion, this study showed for the first time that MADDD, clearly suppressed tumor growth in local prostate cancer tumors. This could potentially be a novel clinical treatment approach for localized prostate cancer.

Solvent-driven actuators based on soft Janus films of homogeneous composition.

A Janus polymer film capable of rapid and reversible folding by triggering with organic solvents is prepared through a template method. Different from most self-folding films with layered structures of different compositions, the reported film can achieve folding function with just a single component by forming a Janus structure. The solvent-driven folding of the film can be remotely controlled not only in air but also in water. In addition, the film is easy to integrate with other materials to fabricate actuators with specific functions for diverse applications.

A robust and refillable magnetic sponge capsule for remotely triggered drug release.

Numerous different delivery systems have been developed for local administration of drugs. However, their service lives generally depend on the payload depletion time and most of them are designed for one time use due to lack of drug replenishment abilities. To address this issue, a refillable magnetic porous polydimethylsiloxane (PDMS) capsule is proposed for remotely controlled drug delivery applications. An inner cavity is built in the sponge scaffold to provide space for drug storage and the refilling is accomplished by injecting drugs with a syringe. The rapid and reversible deformation of the magnetic porous structure under a magnetic field offers a controlled pumping force to push drugs out of the capsule. In this work, low molecular weight (methylene blue, MB, 320 g mol-1) and high molecular weight (bovine serum albumin, BSA, 67 000 g mol-1) molecules were used as model compounds to test and verify the operational principle. This proof-of-concept study has demonstrated the capability of the refillable porous capsule in controlled drug delivery under external magnetic stimuli.

Anti-fouling Coatings of Poly(dimethylsiloxane) Devices for Biological and Biomedical Applications.

Fouling initiated by nonspecific protein adsorption is a great challenge in biomedical applications, including biosensors, bioanalytical devices, and implants. Poly(dimethylsiloxane) (PDMS), a popular material with many attractive properties for device fabrication in the biomedical field, suffers serious fouling problems from protein adsorption due to its hydrophobic nature, which limits the practical use of PDMS-based devices. Effort has been made to develop biocompatible materials for anti-fouling coatings of PDMS. In this review, typical nonfouling materials for PDMS coatings are introduced and the associated basic anti-fouling mechanisms, including the steric repulsion mechanism and the hydration layer mechanism, are described. Understanding the relationships between the characteristics of coating materials and the accompanying anti-fouling mechanisms is critical for preparing PDMS coatings with desirable anti-fouling properties.

Janus ultrathin film from multi-level self-assembly at air-water interfaces.

Ultrathin free-standing Janus films were fabricated at air-water interfaces using azopyridine derivatives and poly(acrylic acid) via multi-level self-assembly on molecular and microscopic scales, which showed distinct asymmetric water wetting abilities on different surfaces.

Fabrication of robust hydrogel coatings on polydimethylsiloxane substrates using micropillar anchor structures with chemical surface modification.

A durable hydrophilic and protein-resistant surface of polydimethylsiloxane (PDMS) based devices is desirable in many biomedical applications such as implantable and microfluidic devices. This paper describes a stable antifouling hydrogel coating on PDMS surfaces. The coating method combines chemical modification and surface microstructure fabrication of PDMS substrates. Three-(trimethoxysilyl)propyl methacrylates containing C═C groups were used to modify PDMS surfaces with micropillar array structures fabricated by a replica molding method. The micropillar structures increase the surface area of PDMS surfaces, which facilitates secure bonding with a hydrogel coating compared to flat PMDS surfaces. The adhesion properties of the hydrogel coating on PDMS substrates were characterized using bending, stretching and water immersion tests. Long-term hydrophilic stability (maintaining a contact angle of 55° for a month) and a low protein adsorption property (35 ng/cm(2) of adsorbed BSA-FITC) of the hydrogel coated PDMS were demonstrated. This coating method is suitable for PDMS modification with most crosslinkable polymers containing C═C groups, which can be useful for improving the anti-biofouling performance of PDMS-based biomedical microdevices.

A handheld electromagnetically actuated fiber optic raster scanner for reflectance confocal imaging of biological tissues.

We present a hand-held device aimed for reflectance-mode confocal imaging of biological tissues. The device consists of a light carrying optical fiber and a miniaturized raster scanner located at the distal end of the fiber. It is fabricated by mounting a polarization maintaining optical fiber on a cantilever beam that is attached to another beam such that their bending axes are perpendicular to each other. Fiber scanner is driven by electromagnetic forces and enables large fiber deflections with low driving currents. Optical resolutions of the system are 1.55 and 8.45 µm in the lateral and axial directions, respectively. Functionality of the system is demonstrated by obtaining confocal images of a fly wing and a human colon tissue sample.

CONTROLLED DELIVERY OF ANTIANGIOGENIC DRUG TO HUMAN EYE TISSUE USING A MEMS DEVICE.

We demonstrate an implantable MEMS drug delivery device to conduct controlled and on-demand, ex vivo drug transport to human eye tissue. Remotely operated drug delivery to human post-mortem eyes was performed via a MEMS device. The developed curved packaging cover conforms to the eyeball thereby preventing the eye tissue from contacting the actuating membrane. By pulsed operation of the device, using an externally applied magnetic field, the drug released from the device accumulates in a cavity adjacent to the tissue. As such, docetaxel (DTX), an antiangiogenic drug, diffuses through the eye tissue, from sclera and choroid to retina. DTX uptake by sclera and choroid were measured to be 1.93±0.66 and 7.24±0.37 µg/g tissue, respectively, after two hours in pulsed operation mode (10 s on/off cycles) at 23°C. During this period, a total amount of 192 ng DTX diffused into the exposed tissue. This MEMS device shows great potential for the treatment of ocular posterior segment diseases such as diabetic retinopathy by introducing a novel way of drug administration to the eye.

Microspheres as resistive elements in a check valve for low pressure and low flow rate conditions.

In this paper we describe a microsphere-based check valve integrated with a micropump. The check valve uses Ø20 µm polystyrene microspheres to rectify flow in low pressure and low flow rate applications (Re < 1). The microspheres form a porous medium in the check valve increasing fluidic resistance based on the direction of flow. Three check valve designs were fabricated and characterized to study the microspheres' effectiveness as resistive elements. A maximum diodicity (ratio of flow in the forward and reverse direction) of 18 was achieved. The pumping system can deliver a minimum flow volume of 0.25 µL and a maximum flow volume of 1.26 µL under an applied pressure of 0.2 kPa and 1 kPa, respectively. A proof-of-concept study was conducted using a pharmaceutical agent, docetaxel (DTX), as a sample drug showing the microsphere check valve's ability to limit diffusion from the micropump. The proposed check valve and pumping concept shows strong potential for implantable drug delivery applications with low flow rate requirements.