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Introduction Melasma is a long‐term acquired disorder characterized by symmetrical darkening in facial regions exposed to sunlight. Although some risk factors have been identified, the etiology remains unclear, and interventions frequently do not totally improve outcomes. Aim It compares the efficacy and side effects of platelet‐rich plasma therapy administered by microneedling versus microinjection to detect any difference in the delivery methods, treatment outcomes, and safety profiles. Methods In this prospective, single‐center, randomized split‐face research, 62 patients' melasma was treated with PRP therapy using microneedling versus microinjection. Microneedling and microinjection were used to apply PRP to the face's two sides. Photographs were obtained before therapy, and the modified Melasma Area and Severity Index (MASI), Physician Global Assessment, and Patient Global Assessment were used for monthly follow‐up evaluation. In order to compare safety and efficacy, adverse events were recorded and statistical analysis was performed. Results A significantly significant difference (p < 0.001) was observed in the mean change in MASI score between microinjection and microneedling. The microneedling group showed a 73.33% improvement while the microinjection group had an 18.33% improvement, both of which were greater than 50%. The microneedling group showed a 46.67% improvement and the microinjection group had a 5% improvement of over 75%. There were no noteworthy negative effects observed. Conclusion PRP therapy with microneedling is superior to microinjection in treating melasma; patients who receive microneedling show noticeably better improvement.

Objectives To evaluate the clinical PK/PD of PTH(1-34) delivered by a novel transdermal drug-coated microneedle patch system (ZP-PTH) for the treatment of osteoporosis. Methods Phase 1 PK studies evaluated the effect of site of administration, patch wear time and dose in normal volunteers, ages 40-85 yrs. Phase 2 was conducted in post-menopausal women with osteoporosis to determine the patch dose response compared to placebo patch and FORTEO® injection. Results Phase 1 ZP-PTH patch delivery demonstrated a rapid PTH plasma pulse profile with Tmax 3 times shorter and apparent T₁/₂ 2 times shorter than FORTEO®. In Phase 2, ZP-PTH 20, 30 and 40 µg doses showed a proportional increase in plasma PTH AUC. Inter-subject and intra-subject AUC variability was similar for all patch doses and comparable to injection. All patch doses produced a significant increase in spine bone mineral density. Unexpectedly, ZP-PTH also produced an early increase in hip bone mineral density, an effect not observed with the injection. Conclusions These studies suggest that this novel ZP-PTH patch system can deliver a consistent and therapeutically relevant PTH PK profile. Based on encouraging Phase 2 safety and efficacy data, the program is advancing into a pivotal Phase 3 clinical study.

The success of protein, peptide and antibody based therapies is evident - the biopharmaceuticals market is predicted to reach $388 billion by 2024 [1], and more than half of the current top 20 blockbuster drugs are biopharmaceuticals. However, the intrinsic properties of biopharmaceuticals has restricted the routes available for successful drug delivery. While providing 100% bioavailability, the intravenous route is often associated with pain and needle phobia from a patient perspective, which may translate as a reluctance to receive necessary treatment. Several non-invasive strategies have since emerged to overcome these limitations. One such strategy involves the use of microneedles (MNs), which are able to painlessly penetrate the stratum corneum barrier to dramatically increase transdermal drug delivery of numerous drugs. This review reports the wealth of studies that aim to enhance transdermal delivery of biopharmaceutics using MNs. The true potential of MNs as a drug delivery device for biopharmaceuticals will not only rely on acceptance from prescribers, patients and the regulatory authorities, but the ability to upscale MN manufacture in a cost-effective manner and the long term safety of MN application. Thus, the current barriers to clinical translation of MNs, and how these barriers may be overcome are also discussed.

Purpose To gather sub-surface in situ images of microneedle-treated human skin, in vivo, using optical coherence tomography (OCT). This is the first study to utilise OCT to investigate the architectural changes that are induced in skin following microneedle application. Methods Steel, silicon and polymer microneedle devices, with different microneedle arrangements and morphologies, were applied to two anatomical sites in human volunteers following appropriate ethical approval. A state-of-the-art ultrahigh resolution OCT imaging system operating at 800 nm wavelength and <3 µm effective axial resolution was used to visualise the microneedle-treated area during insertion and/or following removal of the device, without any tissue processing. Results Transverse images of a microneedle device, in situ, were captured by the OCT system and suggest that the stratified skin tissue is compressed during microneedle application. Following removal of the device, the created microchannels collapse within the in vivo environment and, therefore, for all studied devices, microconduit dimensions are markedly smaller than the microneedle dimensions. Conclusions Microchannels created in the upper skin layers by microneedles are less invasive than previous histology predicts. OCT has the potential to play a highly influential role in the future development of microneedle devices and other transdermal delivery systems.

In general, transgenesis efficiency is largely dependent on the developmental status of eggs for microinjection. We investigated whether the relationship between transgenesis efficiency and cooling eggs in silkworms, Bombyx mori, affects the transgenesis frequencies. First, we performed a microinjection using eggs of different developmental statuses at 25 °C. As a result, the use of eggs at 4 h after egg-laying (hAEL) demonstrated nearly five times greater efficiency in frequency compared to 8 hAEL but no transgenesis was found at 12 hAEL. Second, we examined the use of eggs stored for 5 or 24 h at 10 °C. We found that transgenic silkworms were produced not only 5 hAEL but also 24 hAEL. Finally, in the BmBLOS2 gene knock-out experiment, eggs stored at 10 °C demonstrated knock-out phenotypes even 48 hAEL at the time of injection (G0). These results demonstrate that an egg cooling treatment enables drastically enhanced rates of efficiency for insect genome modification. Our results could be useful in other insects, especially species with an extremely short syncytial preblastodermal stage.

For intradermal (ID) immunisation, novel needle-based delivery systems have been proposed as a better alternative to the Mantoux method. However, the penetration depth of needles in the human skin and its effect on immune cells residing in the different layers of the skin has not been analyzed. A novel and user-friendly silicon microinjection needle (Bella-muTM) has been developed, which allows for a perpendicular injection due to its short needle length (1.4–1.8 mm) and ultrashort bevel. We aimed to characterize the performance of this microinjection needle in the context of the delivery of a particle-based outer membrane vesicle (OMV) vaccine using an ex vivo human skin explant model. We compared the needles of 1.4 and 1.8 mm with the conventional Mantoux method to investigate the depth of vaccine injection and the capacity of the skin antigen-presenting cell (APC) to phagocytose the OMVs. The 1.4 mm needle deposited the antigen closer to the epidermis than the 1.8 mm needle or the Mantoux method. Consequently, activation of epidermal Langerhans cells was significantly higher as determined by dendrite shortening. We found that five different subsets of dermal APCs are able to phagocytose the OMV vaccine, irrespective of the device or injection method. ID delivery using the 1.4 mm needle of a OMV-based vaccine allowed epidermal and dermal APC targeting, with superior activation of Langerhans cells. This study indicates that the use of a microinjection needle improves the delivery of vaccines in the human skin.

The nematode Caenorhabditis elegans is widely employed as a model organism to study basic biological mechanisms. However, transgenic C. elegans are generated by manual injection, which remains low-throughput and labor-intensive, limiting the scope of approaches benefitting from large-scale transgenesis. Here, we report a robotic microinjection system, integrating a microfluidic device capable of reliable worm immobilization, transfer, and rotation, for high-speed injection of C. elegans . The robotic system provides an injection speed 2-3 times faster than that of experts with 7–22 years of experience while maintaining comparable injection quality and only limited trials needed by users to become proficient. We further employ our system in a large-scale reverse genetic screen using multiplexed alternative splicing reporters, and find that the TDP-1 RNA-binding protein regulates alternative splicing of zoo-1 mRNA, which encodes variants of the zonula occludens tight junction proteins. With its high speed, high accuracy, and high efficiency in worm injection, this robotic system shows great potential for high-throughput transgenic studies of C. elegans . Manual injection, which remains low-throughput and labor-intensive, is a technical bottleneck for large-scale genetic studies of C. elegans. Here, the authors report a robotic microinjection system which facilitates injection speed while maintaining injection quality which is comparable to experienced experts.

Microinjection enables the precise delivery of substances into specific areas of small animals, such as zebrafish, whose xenograft models can be a promising platform for developing rapid and personalized cancer therapies. However, manual microinjection exhibits experimental variability and low reproducibility, as it relies on the expertise of researchers. To address these problems, automated microinjection systems have been developed in recent years. In this study, we propose a microrobotic system based on an image recognition AI model that extracts key feature points to define the pericardial space in zebrafish larvae at 2 days post-fertilization. Using the geometric relationships among feature points, the system optimizes the glass capillary insertion motion for precise microinjection. We also introduced a batch agarose microplate that prevents dehydration while stabilizing the larvae, which improved the survival rate compared to the conventional plate (log-rank test, p  < 0.0001). The proposed automation system achieved success rates of 80.8% ( n  = 1129) for microinjection and a 92.1% ( n  = 1143) for survival. Moreover, we successfully injected colorectal cancer cell lines (HCT116 and SW620) into the pericardial space, resulting in an engraftment success rate of 96.2% ( n  = 610). Our system exhibits higher success rates and reproducibility compared to manual microinjection, allowing even inexperienced researchers to perform stable injections. These results demonstrate that our system effectively enhances the efficiency and reproducibility of experiments involving zebrafish-based cancer research and xenograft model generation.

Seamless and minimally invasive three-dimensional interpenetration of electronics within artificial or natural structures could allow for continuous monitoring and manipulation of their properties. Flexible electronics provide a means for conforming electronics to non-planar surfaces, yet targeted delivery of flexible electronics to internal regions remains difficult. Here, we overcome this challenge by demonstrating the syringe injection (and subsequent unfolding) of sub-micrometre-thick, centimetre-scale macroporous mesh electronics through needles with a diameter as small as 100 μm. Our results show that electronic components can be injected into man-made and biological cavities, as well as dense gels and tissue, with >90% device yield. We demonstrate several applications of syringe-injectable electronics as a general approach for interpenetrating flexible electronics with three-dimensional structures, including (1) monitoring internal mechanical strains in polymer cavities, (2) tight integration and low chronic immunoreactivity with several distinct regions of the brain, and (3) in vivo multiplexed neural recording. Moreover, syringe injection enables the delivery of flexible electronics through a rigid shell, the delivery of large-volume flexible electronics that can fill internal cavities, and co-injection of electronics with other materials into host structures, opening up unique applications for flexible electronics. Rolled-up ultraflexible mesh electronics can be injected through a syringe needle of diameter as small as 100 μm into man-made and biological cavities, gels and tissues, where they can unfold and perform sensing operations.

The paternal heredity of obesity and diabetes induced by a high-fat and/or high-sugar diet (Western-like diet) has been demonstrated through epidemiological analysis of human cohorts and experimental analysis, but the nature of the hereditary vector inducing this newly acquired phenotype is not yet well defined. Here, we show that microinjection of either testis or sperm RNA of male mice fed a Western-like diet into naive one-cell embryos leads to the establishment of the Western-like diet-induced metabolic phenotype in the resulting progenies, whereas RNAs prepared from healthy controls did not. Among multiple sequence differences between the testis transcriptomes of the sick and healthy fathers, we noted that several microRNAs had increased expression, which was of interest because this class of noncoding RNA is known to be involved in epigenetic control of gene expression. When microinjected into naive one-cell embryos, one of these small RNA, i.e., the microRNA miR19b, induced metabolic alterations that are similar to the diet-induced phenotype. Furthermore, this pathological phenotype was inherited by the offspring after crosses with healthy partners. Our results indicate that acquired food-induced trait inheritance might be enacted by RNA signalling.