Search

In robot-assisted microsurgery (RAMS), surgeons often face the challenge of operating with minimal feedback, particularly lacking in haptic feedback. However, most traditional desktop haptic devices have restricted operational areas and limited dexterity. This report describes a novel, lightweight, and low-budget wearable haptic controller for teleoperated microsurgical robotic systems. We designed a wearable haptic interface entirely made using off-the-shelf material-PolyJet Photopolymer, fabricated using liquid and solid hybrid 3D co-printing technology. This interface was designed to resemble human soft tissues and can be wrapped around the fingertips, offering direct contact feedback to the operator. We also demonstrated that the device can be easily integrated with our motion tracking system for remote microsurgery. Two motion tracking methods, marker-based and marker-less, were compared in trajectory-tracking experiments at different depths to find the most effective motion tracking method for our RAMS system. The results indicate that within the 4 to 8 cm tracking range, the marker-based method achieved exceptional detection rates. Furthermore, the performance of three fusion algorithms was compared to establish the unscented Kalman filter as the most accurate and reliable. The effectiveness of the wearable haptic controller was evaluated through user studies focusing on the usefulness of haptic feedback. The results revealed that haptic feedback significantly enhances depth perception for operators during teleoperated RAMS.

Corneal epithelial wound healing is a multifaceted process that encompasses cell proliferation, migration, and communication from the corneal stroma. Upon corneal injury, bidirectional crosstalk between the epithelium and stroma via extracellular vesicles (EVs) has been reported. However, the mechanisms by which the EVs from human corneal keratocytes (HCKs), fibroblasts (HCFs), and/or myofibroblasts (HCMs) exert their effects on the corneal epithelium remain unclear. In this study, HCK-, HCF-, and HCM-EVs were isolated and characterized, and human corneal epithelial (HCE) cell migration was assessed in a scratch assay following PKH26-labeled HCK-, HCF-, or HCM-EV treatment. HCE cells proliferative and apoptotic activity following EV treatment was assessed. HCF-/HCM-EVs were enriched for CD63, CD81, ITGAV, and THBS1 compared to HCK-EV. All EVs were negative for GM130 and showed minimal differences in biophysical properties. At the proteomic level, we showed HCM-EV with a log >two-fold change in CXCL6, CXCL12, MMP1, and MMP2 expression compared to HCK-/HCF-EVs; these proteins are associated with cellular movement pathways. Upon HCM-EV treatment, HCE cell migration, velocity, and proliferation were significantly increased compared to HCK-/HCF-EVs. This study concludes that the HCM-EV protein cargo influences HCE cell migration and proliferation, and understanding these elements may provide a novel therapeutic avenue for corneal wound healing.

Corneal fibrosis (or scarring) occurs in response to ocular trauma or infection, and by reducing corneal transparency, it can lead to visual impairment and blindness. Studies highlight important roles for transforming growth factor (TGF)-β1 and -β3 as modulators in corneal wound healing and fibrosis, leading to increased extracellular matrix (ECM) components and expression of α-smooth muscle actin (αSMA), a myofibroblast marker. In this study, human corneal fibroblasts (hCF) were cultured as a monolayer culture (2D) or on poly-transwell membranes to generate corneal stromal constructs (3D) that were treated with TGF-β1, TGF-β3, or TGF-β1 + FAK inhibitor (FAKi). Results show that hCF 3D constructs treated with TGF-β1 or TGF-β3 impart distinct effects on genes involved in wound healing and fibrosis—ITGAV, ITGB1, SRC and ACTA2. Notably, in the 3D construct model, TGF-β1 enhanced αSMA and focal adhesion kinase (FAK) protein expression, whereas TGF-β3 did not. In addition, in both the hCF 2D cell and 3D construct models, we found that TGF-β1 + FAKi attenuated TGF-β1-mediated myofibroblast differentiation, as shown by abrogated αSMA expression. This study concludes that FAK signaling is important for the onset of TGF-β1-mediated myofibroblast differentiation, and FAK inhibition may provide a novel beneficial therapeutic avenue to reduce corneal scarring.

Activation of the mitogen-activated protein kinase (MAPK) signaling pathway regulated by human MAP kinase 1 (MEK1) is associated with the carcinogenesis and progression of numerous cancers. In addition, two active mutations (P124S and E203K) have been reported to enhance the activity of MEK1, thereby eventually leading to the tumorigenesis of cancer. Trametinib is an MEK1 inhibitor for treating EML4-ALK-positive, EGFR-activated, and KRAS-mutant lung cancers. Therefore, in this study, molecular docking and molecular dynamic (MD) simulations were performed to explore the effects of inactive/active mutations (A52V/P124S and E203K) on the conformational changes of MEK1 and the changes in the interaction of MEK1 with trametinib. Moreover, steered molecular dynamic (SMD) simulations were further utilized to compare the dissociation processes of trametinib from the wild-type (WT) MEK1 and two active mutants (P124S and E203K). As a result, trametinib had stronger interactions with the non-active MEK1 (WT and A52V mutant) than the two active mutants (P124S and E203K). Moreover, two active mutants may make the allosteric channel of MEK1 wider and shorter than that of the non-active types (WT and A52V mutant). Hence, trametinib could dissociate from the active mutants (P124S and E203K) more easily compared with the WT MEK1. In summary, our theoretical results demonstrated that the active mutations may attenuate the inhibitory effects of MEK inhibitor (trametinib) on MEK1, which could be crucial clues for future anti-cancer treatment.

A bio-inspired polarization sensor with lenses for navigation was evaluated in this study. Two new calibration methods are introduced, referred to as “central-symmetry calibration” (with an integrating sphere) and “noncontinuous calibration”. A comparison between the indoor calibration results obtained from different calibration methods shows that the two proposed calibration methods are more effective. The central-symmetry calibration method optimized the nonconstant calibration voltage deviations, caused by the off-axis feature of the integrating sphere, to be constant values which can be calibrated easily. The section algorithm proposed previously showed no experimental advantages until the central-symmetry calibration method was proposed. The outdoor experimental results indicated that the indoor calibration parameters did not perform very well in practice outdoor conditions. To establish the reason, four types of calibration parameters were analyzed using the replacement method. It can be concluded that three types can be easily calibrated or affect the sensor accuracy slightly. However, before the sensor is used outdoors every time, the last type must be replaced with the corresponding outdoor parameter, and the calculation needs a precise rotary table. This parameter, which is mainly affected by the spectrum of incident light, is the main factor determining the sensor accuracy. After calibration, the sensor reaches an indoor accuracy of ±0.009° and a static outdoor accuracy of ±0.05° under clear sky conditions. The dynamic outdoor experiment shows a ±0.5° heading deviation between the polarization sensor and the inertial navigation system with a ±0.06° angular accuracy.

Terahertz (THz) radiation has received much attention during the past few decades for its potential applications in various fields, such as spectroscopy, imaging, and wireless communications. To use terahertz waves for data transmission in different application systems, the efficient and rapid modulation of terahertz waves is required and has become an in-depth research topic. Since the turn of the century, research on metasurfaces has rapidly developed, and the scope of novel functions and operating frequency ranges has been substantially expanded, especially in the terahertz range. The combination of metasurfaces and semiconductors has facilitated both new opportunities for the development of dynamic THz functional devices and significant achievements in THz modulators. This paper provides an overview of THz modulators based on different kinds of dynamic tunable metasurfaces combined with semiconductors, two-dimensional electron gas heterostructures, superconductors, phase-transition materials, graphene, and other 2D material. Based on the overview, a brief discussion with perspectives will be presented. We hope that this review will help more researchers learn about the recent developments and challenges of THz modulators and contribute to this field.

Keratoconus is a disease where the cornea becomes cone-like due to structural thinning and ultimately leads to compromised corneal integrity and loss of vision. Currently, the therapeutic options are corrective lenses for early stages and surgery for advanced cases with no in vitro model available. In this study, we used human corneal fibroblasts (HCFs) and compared them to human Keratoconus fibroblasts (HKCs) cultured in a 3-dimensional (3D) model, in order to compare the expression and secretion of specific extracellular matrix (ECM) components. For four weeks, the cells were stimulated with a stable Vitamin C (VitC) derivative ± TGF-β1 or TGF-β3 (T1 and T3, respectively). After four weeks, HKCs stimulated with T1 and T3 were significantly thicker compared with Control (VitC only); however, HCF constructs were significantly thicker than HKCs under all conditions. Both cell types secreted copious amounts of type I and V collagens in their assembled, aligned collagen fibrils, which increased in the degree of alignment upon T3 stimulation. In contrast, only HKCs expressed high levels of corneal scarring markers, such as type III collagen, which was dramatically reduced with T3. HKCs expressed α-smooth muscle actin (SMA) under all conditions in contrast to HCFs, where T3 minimized SMA expression. Fast Fourier transform (FFT) data indicated that HKCs were more aligned when compared to HCFs, independent of treatments; however, HKC’s ECM showed the least degree of rotation. HKCs also secreted the most aligned type I collagen under T3 treatment, when compared to any condition and cell type. Overall, our model for Keratoconus disease studies is the first 3D in vitro tissue engineered model that can mimic the Keratoconus disease in vivo and may be a breakthrough in efforts to understand the progression of this disease.