Ultrasonic Manipulation of Hydrodynamically Driven Microparticles in Vessel Bifurcation: Simulation, Optimization, Experimental Validation, and Potential for Targeted Drug Delivery.

Microrobots driven by multiple external power sources have emerged as promising tools for targeted drug and stem cell delivery in tissue regeneration. However, navigating and imaging these devices within a complex colloidal vascular system at a clinical scale is challenging. Ultrasonic actuators have gained interest in the field of non-contact manipulation of micromachines due to their label-free biocompatible nature and safe operation history. This research presents experimentally validated simulation results of ultrasonic actuation using a novel ultrasonic transducer array with a hemispherical arrangement that generates active traveling waves with phase modulation. Blood flow is used as a carrier force while the direction and path are controlled by blocking undesirable paths using a highly focused acoustic field. In the experiments, the microrobot cluster was able to follow a predefined trajectory and reach the target. The microrobot size, maximum radiation pressure, and focus position were optimized for certain blood flow conditions. The outcomes suggest that this acoustic manipulation module has potential applications in targeted tumor therapy.

Fabrication, Acoustic Characterization and Phase Reference-Based Calibration Method for a Single-Sided Multi-Channel Ultrasonic Actuator.

The ultrasonic actuator can be used in medical applications because it is label-free, biocompatible, and has a demonstrated history of safe operation. Therefore, there is an increasing interest in using an ultrasonic actuator in the non-contact manipulation of micromachines in various materials and sizes for therapeutic applications. This research aims to design, fabricate, and characterize a single-sided transducer array with 56 channels operating at 500 kHz, which provide benefits in the penetration of tissue. The fabricated transducer is calibrated using a phase reference calibration method to reduce position misalignment and phase discrepancies caused by acoustic interaction. The acoustic fields generated by the transducer array are measured in a 300 mm × 300 mm × 300 mm container filled with de-ionized water. A hydrophone is used to measure the far field in each transducer array element, and the 3D holographic pattern is analyzed based on the scanned acoustic pressure fields. Next, the phase reference calibration is applied to each transducer in the ultrasonic actuator. As a result, the homogeneity of the acoustic pressure fields surrounding the foci area is improved, and the maximum pressure is also increased in the twin trap. Finally, we demonstrate the capability to trap and manipulate micromachines with acoustic power by generating a twin trap using both optical camera and ultrasound imaging systems in a water medium. This work not only provides a comprehensive study on acoustic actuators but also inspires the next generation to use acoustics in medical applications.

Acoustically Driven Cell-Based Microrobots for Targeted Tumor Therapy.

Targeted drug delivery using microrobots manipulated by an external actuator has significant potential to be a practical approach for wireless delivery of therapeutic agents to the targeted tumor. This work aimed to develop a novel acoustic manipulation system and macrophage-based microrobots (Macbots) for a study in targeted tumor therapy. The Macbots containing superparamagnetic iron oxide nanoparticles (SPIONs) can serve as drug carriers. Under an acoustic field, a microrobot cluster of the Macbots is manipulated by following a predefined trajectory and can reach the target with a different contact angle. As a fundamental validation, we investigated an in vitro experiment for targeted tumor therapy. The microrobot cluster could be manipulated to any point in the 4 × 4 × 4 mm region of interest with a position error of less than 300 µm. Furthermore, the microrobot could rotate in the O-XY plane with an angle step of 45 degrees without limitation of total angle. Finally, we verified that the Macbots could penetrate a 3D tumor spheroid that mimics an in vivo solid tumor. The outcome of this study suggests that the Macbots manipulated by acoustic actuators have potential applications for targeted tumor therapy.

Holographic Acoustic Tweezers for 5-DoF Manipulation of Nanocarrier Clusters toward Targeted Drug Delivery.

Acoustic tweezers provide unique capabilities in medical applications, such as contactless manipulation of small objects (e.g., cells, compounds or living things), from nanometer-sized extracellular vesicles to centimeter-scale structures. Additionally, they are capable of being transmitted through the skin to trap and manipulate drug carriers in various media. However, these capabilities are hindered by the limitation of controllable degrees of freedom (DoFs) or are limited maneuverability. In this study, we explore the potential application of acoustical tweezers by presenting a five-DoF contactless manipulation acoustic system (AcoMan). The system has 30 ultrasound transducers (UTs) with single-side arrangement that generates active traveling waves to control the position and orientation of a fully untethered nanocarrier clusters (NCs) in a spherical workspace in water capable of three DoFs translation and two DoFs rotation. In this method, we use a phase modulation algorithm to independently control the phase signal for 30 UTs and manipulate the NCs' positions. Phase modulation and switching power supply for each UT are employed to rotate the NCs in the horizontal plane and control the amplitude of power supply to each UT to rotate the NCs in the vertical plane. The feasibility of the method is demonstrated by in vitro and ex vivo experiments using porcine ribs. A significant portion of this study could advance the therapeutic application such a system as targeted drug delivery.

Micromotor Manipulation Using Ultrasonic Active Traveling Waves.

The ability to manipulate therapeutic agents in fluids is of interest to improve the efficiency of targeted drug delivery. Ultrasonic manipulation has great potential in the field of therapeutic applications as it can trap and manipulate micro-scale objects. Recently, several methods of ultrasonic manipulation have been studied through standing wave, traveling wave, and acoustic streaming. Among them, the traveling wave based ultrasonic manipulation is showing more advantage for in vivo environments. In this paper, we present a novel ultrasonic transducer (UT) array with a hemispherical arrangement that generates active traveling waves with phase modulation to manipulate a micromotor in water. The feasibility of the method could be demonstrated by in vitro and ex vivo experiments conducted using a UT array with 16 transducers operating at 1 MHz. The phase of each transducer was controlled independently for generating a twin trap and manipulation of a micromotor in 3D space. This study shows that the ultrasonic manipulation device using active traveling waves is a versatile tool that can be used for precise manipulation of a micromotor inserted in a human body and targeted for drug delivery.

Comparison of the postoperative analgesic effect for infiltration between the popliteal artery and the capsule of the posterior knee and that of periarticular multimodal drug injection in total knee arthroplasty: retrospective study in the immediate postoperative period.

BACKGROUND: The aim of this study is to compare the postoperative analgesic effect of infiltration between the popliteal artery and the capsule of the knee (IPACK) and the effect of periarticular multimodal drug injection (PMDI) in addition to adductor canal block (ACB) after total knee arthroplasty. METHODS: Among patients who received total knee arthroplasty from June 2017 to December 2017, 50 who underwent ACB with additional IPACK and 50 who received ACB with additional PMDI were selected for this study. We compared the postoperative pain numerical rating scale (NRS), the number of times patient-controlled analgesia was administered and the amount administered, the total amount of opioids given, and complications associated with the procedure between the two groups. RESULTS: NRS measured at rest and 45° knee flexion at days 1 and 2 after surgery was significantly lower in the IPACK group than in the PMDI group. The resting NRS measured at day 3 after surgery was also significantly lower in the IPACK group than in the PMDI group, and the NRS at 45° knee flexion measured from day 3 to day 5 showed a significant reduction in the IPACK group. No complications relating to the procedure occurred. CONCLUSIONS: IPACK may be a better option than PMDI for controlling acute phase pain in patients undergoing total knee arthroplasty.

Clinical outcomes of two-stage total knee arthroplasty using articulating cement spacer in patients with infected arthritic knee: A comparison with arthroscopic surgery.

BACKGROUND: The aim of this study was to compare the functional outcomes and recurrence rate of infection between patients who underwent arthroscopic surgery and two-stage total knee arthroplasty (TKA) for infected arthritic knees. METHODS: A retrospective analysis was conducted on 52 patients (52 knees) with advanced knee joint arthritis who underwent arthroscopic surgery or two-stage TKA using articulating cement spacer (ACS) for knee joint infection between January 2009 and November 2013. Of the 52 patients (52 knees), 38 and 14 patients underwent arthroscopic surgery (AS group) and two-stage TKA using ACS (ACS-TKA group), respectively. Patient-reported outcomes (Knee Injury and Osteoarthritis Outcome Score (KOOS) and EuroQol-Visual Analog Scales (EQ-VAS)); range of motion; and recurrence rate of infection were evaluated. RESULTS: Recurrence of infection was observed in 7/38 patients who underwent arthroscopic surgery, all of whom received two-stage TKA using ACS. Regarding the functional outcomes of the ACS-TKA group obtained before conversion to TKA and those of the AS group obtained six months after arthroscopic surgery, the former group had better outcomes for KOOS pain, KOOS activities of daily living, KOOS quality of life, and EQ-VAS. Regarding the functional outcomes of the ACS-TKA group obtained during the last follow-up and after conversion to TKA and those of the AS group who underwent TKA after arthroscopic surgery, no significant between-group differences were observed. The infection recurrence rate was higher in the AS than in the ACS-TKA group. CONCLUSIONS: Considering infection control and functional outcomes, two-stage TKA using ACS can be an effective alternative treatment for patients with infected arthritic knees.

The effect of autotransfusion system in minimally invasive total knee arthroplasty.

PURPOSE: To evaluate the effect of autotransfusion system in minimally invasive total knee arthroplasty (TKA). MATERIALS AND METHODS: Seventy-one patients who underwent unilateral minimally invasive TKA between October 2009 and June 2010 were selected. The first group included 36 patients who received standard vacuum drainage and the second group, 35 patients who underwent autologous retransfusion drainage. In the first group, allogeneic blood transfusion was performed if the postoperative hemoglobin level was <7.0 g/dL or 7.0-8.0 g/dL with the presence of a medical complication and an anemic symptom. The second group received autotransfusion and allogeneic transfusion additionally according to the same criteria. Changes in the pre- and postoperative hemoglobin level, amount of auto- or allotransfusion, and frequency of allogeneic transfusion were assessed. RESULTS: Allogeneic transfusion was required in 13 patients (36.1%) in the first group and four patients (11.4%) in the second group. The mean allogeneic transfusion volume was significantly low in the second group compared to the first group (64.4 mL vs. 278.9 mL; p<0.05). The hemoglobin level on the 1st postoperative day compared to the preoperative level decreased by 22.6% in the first group and 11.7% in the second group. The postoperative hemoglobin level was higher in the second group (p<0.05). CONCLUSIONS: Minimally invasive unilateral TKA with an autotransfusion system can be beneficial in patients with no medical complications because of the decreased allogeneic transfusion.

Formation of quasi-single crystalline porous ZnO nanostructures with a single large cavity.

We report a method for synthesizing quasi-single crystalline porous ZnO nanostructures containing a single large cavity. The microwave-assisted route consists of a short (about 2 min) temperature ramping stage (from room temperature to 120 °C) and a stage in which the temperature is maintained at 120 °C for 2 h. The structures produced by this route were 200-480 nm in diameter. The morphological yields of this method were very high. The temperature- and time-dependent evolution of the synthesized powders and the effects of an additive, vitamin C, were studied. Spherical amorphous/polycrystalline structures (70-170 nm in diameter), which appeared transitorily, may play a key role in the formation of the single crystalline porous hollow ZnO nanostructures. Studies and characterization of the nanostructures suggested a possible mechanism for formation of the quasi-single crystalline porous ZnO nanostructures with an interior space.

Management of focal chondral lesion in the knee joint.

Articular cartilage does not contain vascular, nervous and lymphatic tissue and chondrocytes hardly participate in the healing or repair process of chondral tissue because of being surrounded by plenty of extracellular matrix. Therefore, the injury to articular cartilage frequently requires an operative treatment. The goal of surgical repair of articular cartilage is to regenerate nearly normal chondral tissue and prevent degenerative arthritis caused by the articular cartilage defect. Microfracture is a kind of cartilage repair procedure that makes a fibrin clot containing mesenchymal stem cells in the chondral lesion. Microfracture is a simple procedure but it has a disadvantage that the repaired tissue is fibrocartilage. Autologous chondrocyte implantation has an advantage that it implants fully differentiated chondrocytes to the lesion, which theoretically produces hyaline cartilage. Its disadvantages are that it is a two stage and a costly procedure. Osteochondral autograft transplantation is a one stage procedure and repairs the lesion with hyaline cartilage. But its limitation is the lack of donor site availability. Surgeons who understand the theoretical background, indications, surgical methods, rehabilitation, complications, and clinical course of cartilage repair procedures can achieve the goal of preventing degenerative arthritis.