Ultrasound monitoring of microcirculation: An original study from the laboratory bench to the clinic.

OBJECTIVE: Monitoring microcirculation and visualizing microvasculature are critical for providing diagnosis to medical professionals and guiding clinical interventions. Ultrasound provides a medium for monitoring and visualization; however, there are challenges due to the complex microscale geometry of the vasculature and difficulties associated with quantifying perfusion. Here, we studied established and state-of-the-art ultrasonic modalities (using six probes) to compare their detection of slow flow in small microvasculature. METHODS: Five ultrasonic modalities were studied: grayscale, color Doppler, power Doppler, superb microvascular imaging (SMI), and microflow imaging (MFI), using six linear probes across two ultrasound scanners. Image readability was blindly scored by radiologists and quantified for evaluation. Vasculature visualization was investigated both in vitro (resolution and flow characterization) and in vivo (fingertip microvasculature detection). RESULTS: Superb Microvascular Imaging (SMI) and Micro Flow Imaging (MFI) modalities provided superior images when compared with conventional ultrasound imaging modalities both in vitro and in vivo. The choice of probe played a significant difference in detectability. The slowest flow detected (in the lab) was 0.1885 ml/s and small microvasculature of the fingertip were visualized. CONCLUSIONS: Our data demonstrated that SMI and MFI used with vascular probes operating at higher frequencies provided resolutions acceptable for microvasculature visualization, paving the path for future development of ultrasound devices for microcirculation monitoring.

A Wirelessly Controlled Smart Bandage with 3D-Printed Miniaturized Needle Arrays.

Chronic wounds are one of the most devastating complications of diabetes and are the leading cause of nontraumatic limb amputation. Despite the progress in identifying factors and promising in vitro results for the treatment of chronic wounds, their clinical translation is limited. Given the range of disruptive processes necessary for wound healing, different pharmacological agents are needed at different stages of tissue regeneration. This requires the development of wearable devices that can deliver agents to critical layers of the wound bed in a minimally invasive fashion. Here, for the first time, a programmable platform is engineered that is capable of actively delivering a variety of drugs with independent temporal profiles through miniaturized needles into deeper layers of the wound bed. The delivery of vascular endothelial growth factor (VEGF) through the miniaturized needle arrays demonstrates that, in addition to the selection of suitable therapeutics, the delivery method and their spatial distribution within the wound bed is equally important. Administration of VEGF to chronic dermal wounds of diabetic mice using the programmable platform shows a significant increase in wound closure, re-epithelialization, angiogenesis, and hair growth when compared to standard topical delivery of therapeutics.

Treatment of a Rat Model of LPS-Induced ARDS via Peritoneal Perfusion of Oxygen Microbubbles.

Acute respiratory distress syndrome (ARDS) is a serious respiratory condition that occurs in approximately 10% of patients entering intensive care units around the world, affecting nearly 190,000 patients annually in the United States. Owing to the severity of the condition, conventional methods of oxygenation are often insufficient. However, current alternate methods of oxygenation are associated with contraindications and a mortality rate near 50%. Therefore, a need exists for a safer and more effective method of oxygenation for patients with ARDS. In this work, the feasibility of using intraperitoneal perfusions of oxygen microbubbles-peritoneal microbubble oxygenation (PMO)-to treat lipopolysaccharide-induced ARDS was explored with the objective of showing restoration of normoxic conditions after a single bolus infusion of oxygen microbubbles. Male Wistar rats induced with ARDS via lipopolysaccharide inhalation were treated with PMO at 12-h intervals over a period of 48 h. Their physiological responses were monitored throughout the study, after which necropsy was performed. Response data were then compared with saline control and untreated groups. We conclude that rats experiencing moderate to severe ARDS that were treated with PMO experienced a survival rate 37% higher than animals not given treatment and exhibited increased peripheral blood oxygen saturation when compared with untreated and saline-treated groups. Moreover, those treated with PMO experienced a lower lung wet/dry ratio and less severe lung pathology, indicating a surprising improvement in lung health. Overall, this study demonstrates the ability of PMO to deliver life-sustaining supplemental oxygen to rats suffering from ARDS and warrants further work toward clinical translation.

Advances in monitoring for acute spinal cord injury: a narrative review of current literature.

Spinal cord injury (SCI) is a devastating condition that affects about 17,000 individuals every year in the United States, with approximately 294,000 people living with the ramifications of the initial injury. After the initial primary injury, SCI has a secondary phase during which the spinal cord sustains further injury due to ischemia, excitotoxicity, immune-mediated damage, mitochondrial dysfunction, apoptosis, and oxidative stress. The multifaceted injury progression process requires a sophisticated injury-monitoring technique for an accurate assessment of SCI patients. In this narrative review, we discuss SCI monitoring modalities, including pressure probes and catheters, micro dialysis, electrophysiologic measures, biomarkers, and imaging studies. The optimal next-generation injury monitoring setup should include multiple modalities and should integrate the data to produce a final simplified assessment of the injury and determine markers of intervention to improve patient outcomes.

3D-Printed Hydrogel-Filled Microneedle Arrays.

Microneedle arrays (MNAs) have been used for decades to deliver drugs transdermally and avoid the obstacles of other delivery routes. Hydrogels are another popular method for delivering therapeutics because they provide tunable, controlled release of their encapsulated payload. However, hydrogels are not strong or stiff, and cannot be formed into constructs that penetrate the skin. Accordingly, it has so far been impossible to combine the transdermal delivery route provided by MNAs with the therapeutic encapsulation potential of hydrogels. To address this challenge, a low cost and simple, but robust, strategy employing MNAs is developed. These MNAs are formed from a rigid outer layer, 3D printed onto a conformal backing, and filled with drug-eluting hydrogels. Microneedles of different lengths are fabricated on a single patch, facilitating the delivery of various agents to different tissue depths. In addition to spatial distribution, temporal release kinetics can be controlled by changing the hydrogel composition or the needles' geometry. As a proof-of-concept, MNAs are used for the delivery of vascular endothelial growth factor (VEGF). Application of the rigid, resin-based outer layer allows the use of hydrogels regardless of their mechanical properties and makes these multicomponent MNAs suitable for a range of drug delivery applications.

Development of a Smart Hospital Assistant: Integrating Artificial Intelligence and a Voice-User Interface for Improved Surgical Outcomes.

Patient safety and efficiency are top priorities in any surgical procedure. One effective way to achieve these objectives is to automate the logistical and routine tasks that occur in the operating suite. Inspired by smart assistant technology already widely used in the consumer sector, we engineered the Smart Hospital Assistant (SHA), a smart, voice-controlled virtual assistant that handles natural speech recognition while executing non-surgical functions to aid any surgery. In simulated procedures, the SHA reduced operating time, optimized surgical staff resources, and reduced the number of major touch-points that can lead to surgical site infections. The SHA holds promise not only for use in the operating theater, but also in understaffed healthcare environments where automation can improve healthcare delivery.

Miniaturized Needle Array-Mediated Drug Delivery Accelerates Wound Healing.

A major impediment preventing normal wound healing is insufficient vascularization, which causes hypoxia, poor metabolic support, and dysregulated physiological responses to injury. To combat this, the delivery of angiogenic factors, such as vascular endothelial growth factor (VEGF), has been shown to provide modest improvement in wound healing. Here, the importance of specialty delivery systems is explored in controlling wound bed drug distribution and consequently improving healing rate and quality. Two intradermal drug delivery systems, miniaturized needle arrays (MNAs) and liquid jet injectors (LJIs), are evaluated to compare effective VEGF delivery into the wound bed. The administered drug's penetration depth and distribution in tissue are significantly different between the two technologies. These systems' capability for efficient drug delivery is first confirmed in vitro and then assessed in vivo. While topical administration of VEGF shows limited effectiveness, intradermal delivery of VEGF in a diabetic murine model accelerates wound healing. To evaluate the translational feasibility of the strategy, the benefits of VEGF delivery using MNAs are assessed in a porcine model. The results demonstrate enhanced angiogenesis, reduced wound contraction, and increased regeneration. These findings show the importance of both therapeutics and delivery strategy in wound healing.

Microfluidic Systems with Embedded Cell Culture Chambers for High-Throughput Biological Assays.

The ability to generate chemical and mechanical gradients on chips is important for either creating biomimetic designs or enabling high-throughput assays. However, there is still a significant knowledge gap in the generation of mechanical and chemical gradients in a single device. In this study, we developed gradient-generating microfluidic circuits with integrated microchambers to allow cell culture and to introduce chemical and mechanical gradients to cultured cells. A chemical gradient is generated across the microchambers, exposing cells to a uniform concentration of drugs. The embedded microchamber also produces a mechanical gradient in the form of varied shear stresses induced upon cells among different chambers as well as within the same chamber. Cells seeded within the chambers remain viable and show a normal morphology throughout the culture time. To validate the effect of different drug concentrations and shear stresses, doxorubicin is flowed into chambers seeded with skin cancer cells at different flow rates (from 0 to 0.2 µL/min). The experimental results show that increasing doxorubicin concentration (from 0 to 30 µg/mL) within chambers not only prohibits cell growth but also induces cell death. In addition, the increased shear stress (0.005 Pa) at high flow rates poses a synergistic effect on cell viability by inducing cell damage and detachment. Moreover, the ability of the device to seed cells in a 3D microenvironment was also examined and confirmed. Collectively, the study demonstrates the potential of microchamber-embedded microfluidic gradient generators in 3D cell culture and high-throughput drug screening.

Smart Bandages: The Future of Wound Care.

Chronic non-healing wounds are major healthcare challenges that affect a noticeable number of people; they exert a severe financial burden and are the leading cause of limb amputation. Although chronic wounds are locked in a persisting inflamed state, they are dynamic and proper therapy requires identifying abnormalities, administering proper drugs and growth factors, and modulating the conditions of the environment. In this review article, we discuss technologies that have been developed to actively monitor the wound environment. We also highlight drug delivery tools that have been integrated with bandages to facilitate precise temporal and spatial control over drug release and review automated or semi-automated systems that can respond to the wound environment.