Fig 5 - uploaded by David Fernandez Rivas
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Schematic of the skin (epidermis + dermis) and the subcutis and muscle layer underneath the skin. Thickness are an indication and vary a lot depending on person and skin site [114-116]. Close-up on the epidermis shows the Stratum Spinosum which contains Langerhans cells (L), which are vital in the immune response.

Schematic of the skin (epidermis + dermis) and the subcutis and muscle layer underneath the skin. Thickness are an indication and vary a lot depending on person and skin site [114-116]. Close-up on the epidermis shows the Stratum Spinosum which contains Langerhans cells (L), which are vital in the immune response.

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Needle-free jet injectors have been proposed as an alternative to injections with hypodermic needles. Currently, a handful of commercial needle-free jet injectors already exist. However, these injectors are designed for specific injections, typically limited to large injection volumes into the deeper layers beneath the skin. There is growing eviden...

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... example, most vaccines should target Langerhans cells to maximize efficacy [6,8,15,124]. Langerhans cells are dendritic cells, a type of antigen-presenting cells, which are vital in the first stage of the immune system, as they recognize the invading virus or vaccine [17,18]. As shown in Fig. 5, these Langerhans cells are the most potent immune cell in the Stratum Spinosum, which is in the epidermis [10,20,22,125]. Currently, vaccines are often injected intramuscular, where these dendritic cells are less numerous [14,16]. By directly targeting these Langerhans cells, only a fraction of the dose is required [22], which makes ...

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... 10 This technology employs high-speed jet pressure, creating vibrations and shocks that stimulate mechanotransduction within cells. 11 The device achieves the highest speed among recent needleless injection systems. ...
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Background Acne vulgaris often results in permanent scars, with atrophic scars being the most common type and posing a significant therapeutic challenge due to their prevalence and impact on patients' quality of life. Various treatment options exist, including the use of poly‐ d,l ‐lactic acid delivered via different methods. Objective This study aimed to assess the efficacy and safety of poly‐ d,l ‐lactic acid delivered via laser‐assisted needle‐free microjet injection for treating atrophic scars. Methods Five Korean participants with atrophic facial scars were recruited. Poly‐ d,l ‐lactic acid solution was administered via the Mirajet system in five sessions, with clinical assessments conducted at baseline, before each session, and at 12‐week and 22‐week follow‐ups. Outcome measures included the Global Aesthetic Improvement Scale and patient satisfaction scores. Results Positive results were observed at the 12‐week and 22‐week follow‐ups, with high patient satisfaction and improvements in atrophic scars and skin texture. Mild discomfort and transient side effects were reported, with no adverse events observed during the follow‐up period. Conclusion Poly‐ d,l ‐lactic acid delivered by a laser‐assisted needle‐free microjet injector was judged to be effective for improving atrophic the facial area. Further research, particularly through randomized controlled trials, is needed to validate these findings and assess the longer‐term safety and sustainability of outcomes.
... Plans for development include attaching injection needles or multi-needles to the nozzle and eliminating intermediate barriers to simplify the structure, increasedurability, and adjust temperature for use or artificially cooling for injection. These methods are expected to expand the scope of application, overcoming the drawbacks of slow-speed needle-type automatic injectors.3,8,9 ...
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Introduction Striae distensae (SD), or stretch marks, result from rapid stretching of the skin due to various factors. Conventional treatments often yield unsatisfactory results, leading to the exploration of alternative methods. Laser‐induced microjet technology offers a promising approach for drug delivery to target areas. This study investigates the efficacy of using a microjet injector with poly‐d,l‐lactic acid for treating SD. Methods Four female participants with SD were treated with poly‐d,l‐lactic acid solution using a microjet injector over five sessions. Patients were assessed based on severity scales before and after treatment. Topical anesthetics were applied to minimize discomfort. Injection techniques were optimized to reduce side effects such as bleeding and pain. Results All patients showed significant improvement in SD appearance after 5–7 treatments. Assessment scales indicated positive outcomes both immediately after treatment and at the 32‐week follow‐up. Minimal side effects, primarily petechiae, were observed. Discussion Laser‐induced microjet technology offers several advantages, including rapid drug delivery and mechanotransduction effects, promoting skin regeneration. Poly‐d,l‐lactic acid injections demonstrated effectiveness in treating SD, particularly when delivered via microjet injectors. Patients expressed high satisfaction due to the procedure's minimal invasiveness and quick recovery. Conclusion Utilizing a needleless microjet injector with poly‐d,l‐lactic acid shows promise as a treatment for SD, typically requiring 5–7 sessions for optimal results. Mild petechiae may occur as a common side effect. This approach offers an effective and minimally invasive alternative for addressing this common cosmetic concern.
... In this work, we looked into the dynamics of a high-speed microfluidic jet penetrating a pool. These jets are comparable in size and momentum to those produced in needle-free applications (Schoppink & Rivas 2022). A validation process was done through both qualitative and quantitative comparisons with other numerical results, experiments and theoretical predictions. ...
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Studying liquid jet impacts on a liquid pool is crucial for various engineering and environmental applications. During jet impact, the free surface of the pool deforms and a cavity is generated. Simultaneously, the free surface of the cavity extends radially outward and forms a rim. Eventually the cavity collapses by means of gas inertia and surface tension. Our numerical investigation using an axisymmetric model in Basilisk C explores cavity collapse dynamics under different impact velocities and gas densities. We validate our model against theory and experiments across a previously unexplored parameter range. Our results show two distinct regimes in the cavity collapse mechanism. By considering forces pulling along the interface, we derive scaling arguments for the time of closure and maximum radius of the cavity, based on the Weber number. For jets with uniform constant velocity from tip to tail and $We \leqslant 150$ , the cavity closure is capillary-dominated and happens below the surface (deep seal). In contrast, for $We \geqslant 180$ the cavity closure happens above the surface (surface seal) and is dominated by the gas entrainment and the pressure gradient that it causes. Additionally, we monitor gas velocity and pressure throughout the impact process. This analysis reveals three critical moments of maximum gas velocity: before impact, at the instant of cavity collapse and during droplet ejection following cavity collapse. Our results provide information for understanding pollutant transport during droplet impacts on large bodies of water, and other engineering applications, like additive manufacturing, lithography and needle-free injections.
... These jet injectors operate by propelling a small amount of medication through a narrow opening using compressed gas or a spring. The key advantage of this method is that it eliminates the pain and fear associated with needles and local anesthesia administration [10,17]. Dental jet injectors, such as Syrijet (Keystone Industries, USA) and Panjet (Wright Health Group Limited, UK), have been adopted since the 1970s and can effectively anesthetize the target tissue while improving patient comfort [18]. ...
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Background: The dreaded sensation of pain in the dental chair has a significant impact on children’s behavior. This study aimed to compare and contrast the perception of pain and patient behavior between the use of INJEX and the conventional syringe needle technique during pulpotomy among children. Methods: A randomized clinical trial was designed and conducted among pediatric dentistry patients aged 6–12 years old. Fifty-eight children were divided into two groups, conventional syringe needle and INJEX, using simple randomization method applying the sequentially numbered, opaque, sealed envelope method of allocation concealment. Anesthesia was administered to the groups as local infiltration by a single operator following routine behavior guidance techniques. After 3 min, pulpotomy was performed using the standard protocol. The Face, Legs, Activity, Cry, Consolability (FLACC) scale and Wong–Baker FACES Pain Rating Scale (WBS) were used to assess the intensity of pain, while the Frankl behavior rating scale (FBRS) was used to assess the children’s behavior. Results: During anesthesia, most of the participants in the INJEX group (median = 3) had higher FBRS scores compared with the conventional syringe needle group (median = 2), and the difference was very highly significant (p-value < 0.001). Analyzing the FLACC scores during local anesthesia administration revealed a high statistical significance (p-value < 0.01) across the two groups. A very high statistically significant difference (p-values < 0.001) with higher WBS scores for pain intensity was seen in the group using conventional syringe needles. Conclusions: INJEX administration significantly reduced the intensity of pain experienced by the children and helped maintain a positive attitude among them during pulpotomy. It provided a positive and comfortable experience for both the child and the practitioner. Therefore, it can serve as an excellent alternative to conventional needle anesthesia.
... Over the years, scientists have learnt to use bubbles in various applications. These include drug delivery, where bubbles serve as carriers for medications, lithotripsy and histotripsy for breaking down kidney stones and for tissue ablation, respectively, high-intensity focused ultrasound (HIFU) treatment for noninvasive treatment, needle-free injection methods, high-contrast ultrasound imaging for medical diagnostics, thrombolysis, and many more [3][4][5][6][7][8][9][10][11][12] . To gain better control over these biological applications, it is essential to understand the response of these bubbles to the changes in their surroundings. ...
Article
Numerical methods for the simulation of cavitation processes have been developed for more than 50 years. The rich variety of physical phenomena triggered by the collapse of a bubble has several applications in medicine and environmental science but requires the development of sophisticated numerical methods able to capture the presence of sharp interfaces between fluids and solid/elastic materials, the generation of shock waves and the development of non-spherical modes. One important challenge faced by numerical methods is the important temporal and scale separation inherent to the process of bubble collapse, where many effects become predominant during very short time lapses around the instant of minimum radius when the simulations are hardly resolved. In this manuscript, we provide a detailed discussion of the parameters controlling the accuracy of direct numerical simulation in general non-spherical cases, where a new theoretical analysis is presented to generalize existing theories on the prediction of the peak pressures reached inside the bubble during the bubble collapse. We show that the ratio between the gridsize and the minimum radius allows us to scale the numerical errors introduced by the numerical method in the estimation of different relevant quantities for a variety of initial conditions.
... 51 Two notable examples include the ablative fractional erbium-doped yttrium aluminum garnet laser (AFL-Er:YAG) and the ablative fractional carbon dioxide laser (AFL-CO 2 ). 52 Both of these lasers have excellent tolerability and safety in humans and promote faster tissue recovery, resulting in a quick onset of action, as shown in Fig. 5. 30 For instance, they can effectively and safely deliver 5-fluorouracil cream to treat hypertrophic scars, 53 triamcinolone cream for areata alopecia, 54 or epidermal growth factor and AFL together to treat acne scars. 55 Table 1 summarizes the key distinctions between these two lasers. ...
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The presence of the uppermost layer of the skin, referred to as the stratum corneum (SC), restricts the therapeutic efficacy of many drugs by acting as a barrier for drug molecules. Consequently, only a small number of molecules are likely to reach the intended target region. To overcome this impediment, transdermal drug delivery (TDD) that ablates the SC was developed, resulting in the formation of micropores that develop in a defined region of the skin's outer layer, which facilitates the delivery of extremely hydrophilic medications and macromolecules throughout the skin. The process of SC ablation involves the use of a range of physical techniques, which may be categorized as element-based heating, radiofrequency, laser, and suction ablation. Lately, there has been an increasing fascination with using physical ablative methods for skin treatment. Studies have shown that using ablative methods to improve drug delivery has many benefits, such as higher bioavailability, shorter treatment duration, and rapid recovery of the skin barrier. This review presents a comprehensive overview of the principles underlying a variety of methods for SC ablation, focusing on their potential for dramatically increasing skin absorption of drug molecules, delivering vaccines as a non-invasive alternative to injections, facilitating the delivery of macromolecules, and their application in drug delivery for chronic diseases like Alzheimer's disease or diabetes mellitus. In addition, we summarize some previous studies that compared the effectiveness of various SC ablation methods.
... In those scenarios, the cavity collapse leads to impressive amplifications of the jet velocity compared to their initiation mechanism, where the jet velocity varies from low subsonic [7][8][9][10] to supersonic states [11]. The enhancement of such energy-focusing mechanisms through the utilization of single/multiple cavities is of great importance, e.g., for alternative medical therapies of needle-based injections [12] or soft material perforation [13], where stable jets with high velocities and small volume are desired. ...
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We reveal for the first time by experiments that within a narrow parameter regime, two cavitation bubbles with identical energy generated in antiphase develop a supersonic jet. High-resolution numerical simulation shows a mechanism for jet amplification based on toroidal shock wave and bubble necking interaction. The microjet reaches velocities in excess of 1000 m s −1. We demonstrate that potential flow theory established for Worthington jets accurately predicts the evolution of the bubble gas-liquid interfaces unifying compressible and incompressible jet amplification.
... Cavitation, a phenomenon characterized by the formation and subsequent collapse of vapor-filled bubbles in a liquid, has attracted the attention of researchers and engineers in various disciplines. The complex fluid dynamics of cavitation bubbles play a pivotal role in numerous natural processes and engineering applications, ranging from ocean [1], biomedical [2,3], and environmental [4,5] fields. The dynamics of a single cavitation bubble in quiescent liquids have been extensively explored. ...
... PLEASE CITE THIS ARTICLE AS DOI: 10.1063/5.0195954 3 unbounded water case. In addition, a broader counter jet than in the case of the flat free surface was observed, and two liquid jets on the droplet surface can be formed under specific ...
... However, in real bubble-droplet interaction cases, a thin liquid injection is observed [45]. This type of ventilating jet mechanism is being developed for many applications, including needle-free injection [3] and surface cleaning [4,68]. This is the author's peer reviewed, accepted manuscript. ...
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In this study, complicated nonlinear interactions of a single laser-induced cavitation bubble inside a millimetric water droplet were numerically investigated using a fully compressible three-phase homogeneous model. A general condensation phase-change model and high-resolution interface-capturing schemes were adopted to accurately predict the bubble collapsing and rebound stages, as well as strongly deformable droplet interface evolutions. The numerical model was validated using experimental data in terms of the equivalent bubble radius until the second collapse stage, and good quantitative agreements were achieved. The variation in the droplet surface velocity was detected and could better reveal the mechanism underlying the complicated bubbles and droplet interactions, particularly in droplet surface splash dynamics. Subsequently, the complex bubble-droplet interaction phenomena were studied by investigating the ratio of the maximum bubble radius to the initial droplet radius. The numerical results show that the bubble collapsing time decreases monotonically with an increase in the bubble-droplet radius ratio. The droplet surface instabilities became more dominant as the radius ratio increased. In addition, four distinct patterns of droplet motion, namely, stable, multi-spike, ventilating jet, and splashing phenomena, were captured. Finally, the specific mechanisms leading to droplet surface jetting were identified.
... [4][5][6] Therefore, a needle-free injector, which injects liquid as a high-speed microjet into the body, has been developed in recent years. [7][8][9][10] Commercialized needle-free injectors, which commonly use a diffused jet, are reported to cause significant pain during injection. [11][12][13][14] A laser-induced microjet with a focused tip is expected to be a solution because of the lower stress induced at the injection site and the higher efficiency of liquid transportation. ...
Article
The control of the velocity of a high-speed laser-induced microjet is crucial in applications such as needle-free injection. Previous studies have indicated that the jet velocity is heavily influenced by the volumes of secondary cavitation bubbles generated through laser absorption. However, there has been a lack of investigation of the relationship between the positions of secondary cavitation bubbles and the jet velocity. In this study, we investigate the effects of secondary cavitation on the jet velocity of laser-induced microjets extracted using explainable artificial intelligence (XAI). An XAI is used to classify the jet velocity from images of secondary cavitation and to extract features from the images through visualization of the classification process. For this purpose, we run 1000 experiments and collect the corresponding images. The XAI model, which is a feedforward neural network (FNN), is trained to classify the jet velocity from the images of secondary cavitation bubbles. After achieving a high classification accuracy, we analyze the classification process of the FNN. The predictions of the FNN, when considering the secondary cavitation positions, show a higher correlation with the jet velocity than the results considering only secondary cavitation volumes. Further investigation suggested that secondary cavitation that occurs closer to the laser focus position has a higher acceleration effect. These results suggest that the velocity of a high-speed microjet is also affected by the secondary cavitation position.
... This category of injector utilizes laser pulses to produce vapor bubbles, generating pressure energy for propelling a jet through a nozzle. A notable advantage of the laserinduced microjet injector lies in its precise energy deposition control, enabling the accurate injection of µL-range volumes to specific depths across the superficial to deep dermal layers [30]. In a recent study, Han et al. [31] conducted a randomized, double-blinded trial, which employed a split-face design, to compare the outcomes of using the laser-induced microjet injector (MIRAJET; JSK Biomed, Seoul, Republic of Korea) versus conventional needle injection for delivering PLA filler to achieve skin enhancement and rejuvenation. ...
... Laser-driven needle-free injection offers precise filler administration for skin rejuvenation, resulting in even distribution, improved clinical effectiveness, reduced discomfort, and fewer side effects, making it a promising alternative for filler injection [31]. A drawback of laser-based jet injectors is their lower cost-effectiveness, as they require laser systems with substantially higher costs for operation and maintenance [30]. ...
... Laser-assisted needle-free injection also has disadvantages in scar treatment since it typically has restricted penetration depth in thick and fibrous tissue [30]. For instance, after being injected using a laser-assisted jet injector, PLA was discovered to be localized only in the uppermost part of the dermis (papillary dermis), sparing the mid-and lower dermis [27]. ...
Article
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Acne scars, particularly atrophic ones, present a persistent challenge in cosmetic medicine and surgery, requiring extended and multifaceted treatment approaches. Poly-(lactic acid) injectable fillers show promise in managing atrophic acne scars by stimulating collagen synthesis. However, the utilization of needle-free injectors for delivering poly-(lactic acid) into scars remains an area requiring further exploration. In this article, a summary of the latest advancements in needle-free jet injectors is provided, specifically highlighting the variations in jet-producing mechanisms. This summary emphasizes the differences in how these mechanisms operate, offering insights into the evolving technology behind needle-free injection systems. The literature review revealed documented cases focusing on treating atrophic acne scars using intralesional poly-(lactic acid) injections. The results of these clinical studies could be supported by separate in vitro and animal studies, elucidating the feasible pathways through which this treatment operates. However, there is limited information on the use of needle-free jet injectors for the intradermal delivery of poly-(lactic acid). Clinical cases of atrophic acne scar treatment are presented to explore this novel treatment concept, the needle-free delivery of poly-(lactic acid) using a jet pressure-based injector. The treatment demonstrated efficacy with minimal adverse effects, suggesting its potential for scar treatment. The clinical efficacy was supported by histological evidence obtained from cadaver skin, demonstrating an even distribution of injected particles in all layers of the dermis. In conclusion, we suggest that novel needle-free injectors offer advantages in precision and reduce patient discomfort, contributing to scar improvement and skin rejuvenation. Further comprehensive studies are warranted to substantiate these findings and ascertain the efficacy of this approach in scar treatment on a larger scale.