Palatal injections are considered to be one of the most painful dental procedures. As a result, it was important to find alternatives to this painful injection to improve children\'s cooperation. The dental literature mentioned using EMLA cream as a possible alternative to conventional injections, but its anesthetic effect was debated. Therefore, it was valuable to research the impact of microneedle patches to enhance the effectiveness of this cream. The purpose of this randomized controlled clinical trial was to compare the effectiveness of different methods of anesthesia and pain levels in children aged 7-11 years. The study compared the use of EMLA cream, EMLA with microneedles, and conventional palatal injections. A total of 90 children were randomly assigned to three groups: Group 1 received conventional palatal anesthesia (control), Group 2 received EMLA cream only, and Group 3 received EMLA with microneedles. Pain levels were assessed using the FLACC and Wong-Baker scales at three different time points: T1(during anesthesia), T2(on palatal probing), and T3(during extraction). The FLACC scale revealed a significant difference in pain between groups only at T1 (P value = 0.000). It was found that the conventional palatal injection group had a higher pain level than the EMLA cream-only group and the group using microneedle patches with EMLA cream (P value = 0.000). However, the other groups did not show significant differences in pain levels during the anesthesia (P value  = 1.00). Similarly, the Wong-Baker scale also demonstrated a statistically significant difference in pain between groups only at T1 (P value  = 0.000). It was found that the conventional palatal injection group had a higher pain level than the EMLA cream-only group and the group using microneedle patches with EMLA cream (P value  = 0.000). However, the other groups did not show significant differences in pain levels during the anesthesia (P value  = 0.091). The study concludes that both EMLA cream alone and EMLA with microneedles can be used as an alternative to conventional palatal anesthesia for children.

Alopecia areata (AA) is a chronic autoimmune disease characterized by bald patches in certain areas of the body, especially the scalp. Minoxidil (MNX), as a first-line treatment of AA, effectively induces hair growth. However, oral and topical administration pose problems, including low bioavailability, risk of uncontrolled hair growth, and local side effects such as burning hair loss, and scalp irritation. In the latest research, MNX was delivered to the skin via microneedle (MN) transdermally. The MNX concentration was distributed throughout the needle so that drug penetration was reduced and had the potential to irritate. In this study, we formulated MNX into three-layer dissolving microneedles (TDMN) to increase drug penetration and avoid irritation. Physicochemical evaluation, parafilm, was used to evaluate the mechanical strength of TDMN and showed that TDMN could penetrate the stratum corneum. The ex-vivo permeation test showed that the highest average permeation result was obtained for TDMN2, namely 165.28 ± 31.87 ug/cm2, while for Minoxidil cream it was 46.03 ± 8.5 ug/cm2. The results of ex vivo and in vivo dermatokinetic tests showed that the amount of drug concentration remaining in the skin from the TDMN2 formula was higher compared to the cream preparation. The formula developed has no potential for irritation and toxicity based on the HET-CAM test and hemolysis test. TDMN is a promising alternative to administering MNX to overcome MNX problems and increase the effectiveness of AA therapy.

OBJECTIVE: This randomized trial assessed for the first time the efficacy of coronally advanced flap (CAF) followed by micro-needling (MN) in contrast to CAF with acellular dermal matrix (ADM) on gingival thickness (GT, primary outcome), keratinized tissue width (KTW), clinical attachment level (CAL), probing depth (PD), recession depth (RD), recession width (RW), recession reduction (Rec-Red), complete root coverage (CRC) and percentage of root coverage (all secondary outcomes) in management of RT1 gingival recession in patients with thin gingival phenotype.
METHODS: A total of 24 patients (n = 24) with a thin gingival phenotype and single RT1 gingival recession in the aesthetic zone were randomly allocated to test- (CAF + MN; n = 12) or control group (CAF + ADM; n = 12). All clinical parameters were evaluated at baseline, 3 and 6 months.
RESULTS: Both groups independently demonstrated significant gain in GT, RW, RD, CAL, PD, Rec-Red, CRC and percentage of root coverage, with reduced PI and BOP (p < .05) at 3 and 6 months, without intergroup differences (p > .05). At 6 months, KTW gain was significantly higher in CAF + MN (5.08 ± 0.9 mm) than in CAF + ADM-group (4.25 ± 1.06 mm; p < .05). Stepwise linear regression model with GT as dependent variable showed that base-line GT was the only statistically significant predictor for GT with a direct correlation between base-line GT and GT after 6 months.
CONCLUSIONS: CAF followed by MN could represent a promising graft-less approach for increasing gingival thickness, comparable to CAF with ADM, with superior keratinized tissue width improvement, in the treatment of RT1 recession defects in patients with thin gingival phenotype.

Microneedle transdermal administration and low-frequency ultrasound represent two important physical penetration-promoting methods for enhancing drug penetration. This article aims to investigate and compare the effects of drug penetration enhancement through transdermal administration using vibrating microneedles versus low-frequency sonophoresis. In Vitro permeation studies were conducted using Valia-Chien double chamber diffusion cells to evaluate the transdermal delivery of tetramethylpyrazine hydrochloride (TMPH). The TMPH concentration in the receiving compartment was determined using high-performance liquid chromatography (HPLC). Several combinations of microneedles and ultrasound settings were investigated, including different needle heights, vibration frequencies, exposure times, and assorted distances of ultrasound horn and skin. The results revealed the vibrating microneedle system as the most efficacious treatment to increase the TMPH permeability into the rat skin. The combination of a larger needle, higher frequency, and a 3-min exposure led to a 41.92-fold increase in cumulative permeability compared to the control group. The ultrasound treatment exhibited a moderate enhancement effect on TMPH skin penetration. Using a horn-to-skin distance of 3 mm and a 3-min exposure resulted in a 4.34-fold increase in TMPH cumulative permeation compared to the control group. It could be concluded that while both the vibrating microneedle and the low-frequency ultrasound systems act as penetration enhancers for promoting the TMPH permeation through the skin, the vibrating microneedle system notably demonstrates a more effective penetration-promoting effect.

BACKGROUND: Studies have reported promising results of mesenchymal stem cell therapies for skin aging. However, in the use of mesenchymal stem cells, some drawbacks including rarely possible tumorigenicity and low engraftment rates have limited their widespread clinical use. Adipose tissue stem cell-derived exosomes (ASCEs) are emerging as effective cell-free therapeutic agents.
OBJECTIVE: It was evaluated the clinical efficacy of combining the application of human ASCE-containing solution (HACS) with microneedling to treat facial skin aging.
METHODS: A 12-week, prospective, randomized, split-face, comparative study was conducted. Twenty-eight individuals underwent three treatment sessions separated by 3-week intervals and were followed up for 6 weeks after the last session. At each treatment session, HACS and microneedling were administered to one side of the face, and normal saline solution and microneedling were administered to the other side as a control.
RESULTS: The Global Aesthetic Improvement Scale score was significantly higher on the HACS-treated side than on the control side at the final follow-up visit (p = 0.005). Objective measurements obtained by different devices including PRIMOS Premium, Cutometer MPA 580, Corneometer CM 825, and Mark-Vu confirmed greater clinical improvements in skin wrinkles, elasticity, hydration, and pigmentation on the HACS-treated side than on the control side. The results of the histopathological evaluation were consistent with the clinical findings. No serious adverse events were observed.
CONCLUSIONS: These findings demonstrate that combined treatment using HACS and microneedling is effective and safe for treating facial skin aging.

BACKGROUND: Crossbow-medicine needle therapy (microneedle roller combined with crossbow-medicine) is one of the external treatment methods of Miao Medicine in China. It is a way of combining acupuncture with Chinese herbal medicine, which is widely used in clinical treatment of pain.
OBJECTIVE: To observe the transdermal absorption promoting effect of microneedle roller via transdermal administration, and to discuss the transdermal absorption characteristics and the safety of crossbow-medicine needle therapy.
METHODS: Based on the determination of the content of the main components of crossbow-medicine prescription in our previous research, the present experiment was conducted in-vitro and in-vivo experiments and the skin of rats was used as the penetration barrier. For in-vitro experiment, the modified Franz diffusion cell method was used to determine the transdermal absorption rate and 24h cumulative transdermal absorption amount of the active ingredients of crossbow-medicine liquid. For in-vivo experiment, tissue homogenization was applied to compare the skin retention amount and plasma concentration of crossbow-medicine liquid absorbed at different time points via the aforementioned two modes of administration. Furthermore, the effect of crossbow-medicine needle on the morphological structure of rat skin stratum corneum was detected by hematoxylin-eosin (HE) staining. The safety of crossbow-medicine needle therapy was evaluated according to the scoring criteria of the skin irritation test.
RESULTS: 1. In-vitro experiment: In the microneedle-roller group and crossbow-medicine liquid application group, the effect of transdermal delivery was identified in all the four ingredients of anabasine, chlorogenic acid, mesaconitine and hypaconitine. The 24h cumulative transdermal absorption amount and transdermal absorption rate of each ingredient in microneedle-roller group were significantly higher than those in crossbow-medicine liquid application group (all P < 0.05). 2. In-vivo experiment: Both microneedle-roller and crossbow-medicine liquid application could promote the transdermal absorption of the active ingredients of the drug in the skin and retain in the skin structure. After 8h of administration, the total retention amount of anabasine, chlorogenic acid, mesaconitine and hypaconitine in the skin of rats in the former group was significantly higher than that in the latter group (all P < 0.05). 3. HE staining: In the blank group, the stratum corneum showed an evenly zonal distribution on the active epidermis, and had a close connection with the epidermis, without exfoliation or cell dissociation of the stratum corneum. The crossbow-medicine liquid group had a relatively complete stratum corneum, with a small proportion of exfoliation or cell dissociation, loose arrangement and loose connection with the epidermis. In the microneedle-roller group, the skin had pore channels, and the stratum corneum was loose and exfoliated, which showed zonal distribution in a free state and a high degree of separation. The crossbow-medicine needle group had loose the stratum corneum, broken and exfoliated, which was separated from the active epidermis and showed zonal distribution in a free state. 4.
RESULTS: No obvious erythema, edema and skin protuberance were observed in the skin of rats treated with microneedle roller, crossbow-medicine liquid and crossbow-medicine needle. Additionally, the skin irritative response score was 0.
CONCLUSIONS: Microneedle roller can promote the transdermal absorption of crossbow-medicine liquid, and crossbow-medicine needle therapy has good safety.

Intravenous cannulation is experientially traumatic to children. To minimize this, EMLA® is applied on the would-be-cannulated area before IV cannula insertion. However, the time to achieve its maximum efficacy may be affected due to incomplete cutaneous absorption and the duration of application. The latter may be a limiting factor in a busy healthcare facility. The usage of dissolvable maltose microneedles may circumvent this problem by introducing micropores that will facilitate EMLA® absorption. A randomized phase II cross-over trial will be conducted to compare the Visual Analogue Scale (VAS) pain scores and skin conductance algesimeter index between 4 different interventions (1 fingertip unit (FTU) of EMLA® with microneedle patch for 30 min before cannulation; 0.5 FTU of EMLA® with microneedle patch for 30 min; 1 FTU of EMLA® with microneedle for 15 min; 1 FTU of EMLA® with sham patch for 30 min). A total of 26 pediatric patients with thalassemia aged between 6 and 18 years old and requiring blood transfusion will be recruited in this trial. During the visits, the VAS scores and skin conductance algesimeter index at venous cannulation will be obtained using the VAS rulers and PainMonitor™ machine, respectively. The trial will commence in August 2021 and is anticipated to end by August 2022.

BACKGROUND: Facial cosmetic conditions can manifest as post-inflammatory erythema, scars, pigmentation, enlarged pores, skin laxity, and photoaging. The microneedle fractional radiofrequency system (MFRS) is a new device that combines radiofrequency and microneedles and has been widely used for skin rejuvenation. Since MFRS is an invasive technique, this study aimed to evaluate whether the skin barrier functions might be impaired by this treatment, revealed by skin sensitivity and exacerbation of melasma.
METHODS: Twenty patients with Fitzpatrick grades III-IV facial conditions (skin laxity with melasma, n = 9; post-inflammatory erythema and scars, n = 5; and enlarged pores, n = 6) and treated with MFRS were enrolled. Transepidermal water loss (TEWL, using Ultrascan UC22), skin sensitivity (ten-item Sensitive Scale, SS-10), melanin index (MI), melasma area and severity index (MASI), red areas (VISIA), and thickness and density of the epidermis and dermis on ultrasonography were compared between baseline and 6 months after all treatment sessions.
RESULTS: Twenty patients completed a 6-month follow-up after two MFRS treatments. During days 1-3 post-treatment, the TEWL values gradually increased to the peak and decreased to baseline levels (BD) on day 7. There was no significant difference in TEWL compared with baseline in month (M) 1, M3, and M6. There were no significant changes in the thickness and density of the epidermis. Although the thickness and density of the dermis increased, there was no significant difference compared to baseline. There was no significant difference in the MI, MASI, and SS-10 score before and after MFRS treatment. After treatment with MFRS, the red area and scarring reduced significantly (p < .01), and no significant difference was observed in other patients.
CONCLUSIONS: MFRS is a safe and effective treatment for facial cosmetic conditions. The skin barrier function is not impaired by MFRS treatment, since it does not cause skin sensitivity or melasma exacerbation.

BACKGROUND: New strategies to increase measles and rubella vaccine coverage, particularly in low- and middle-income countries, are needed if elimination goals are to be achieved. With this regard, measles and rubella vaccine microneedle patches (MRV-MNP), in which the vaccine is embedded in dissolving microneedles, offer several potential advantages over subcutaneous delivery. These include ease of administration, increased thermostability, an absence of sharps waste, reduced overall costs and pain-free administration. This trial will provide the first clinical trial data on MRV-MNP use and the first clinical vaccine trial of MNP technology in children and infants.
METHODS: This is a phase 1/2, randomized, active-controlled, double-blind, double-dummy, age de-escalation trial. Based on the defined eligibility criteria for the trial, including screening laboratory investigations, 45 adults [18-40 years] followed by 120 toddlers [15-18 months] and 120 infants [9-10 months] will be enrolled in series. To allow double-blinding, participants will receive either the MRV-MNP and a placebo (0.9% sodium chloride) subcutaneous (SC) injection or a placebo MNP and the MRV by SC injection (MRV-SC). Local and systemic adverse event data will be collected for 14 days following study product administration. Safety laboratories will be repeated on day 7 and, in the adult cohort alone, on day 14. Unsolicited adverse events including serious adverse events will be collected until the final study visit for each participant on day 180. Measles and rubella serum neutralizing antibodies will be measured at baseline, on day 42 and on day 180. Cohort progression will be dependent on review of the unblinded safety data by an independent data monitoring committee.
CONCLUSIONS: This trial will provide the first clinical data on the use of a MNP to deliver the MRV and the first data on the use of MNPs in a paediatric population. It will guide future product development decisions for what may be a key technology for future measles and rubella elimination.
BACKGROUND: Pan-African Clinical Trials Registry 202008836432905 .
RESULTS: gov NCT04394689.

OBJECTIVE: This study aimed to evaluate the safety and efficacy of a novel therapeutic strategy, a microneedle fractional radiofrequency system, for hand rejuvenation.
METHODS: Sixteen subjects were enrolled in a self-controlled evaluator-blind prospective trial. All subjects received three microneedle fractional radiofrequency treatments at 4 weeks intervals. Hand volume was evaluated through subjective (Hand Volume Rating Scale) and quantitative measurements. Patients were also assessed on the Global Aesthetic Improvement Scale using digital photographs. Patients were followed up at 1, 3, and 6 months after the last radiofrequency treatment.
RESULTS: Statistically significant improvements on the Global Aesthetic Improvement Scale and Hand Rating Volume Scale were noted (p < 0.05). Compared with the control side, the treated hand showed a 44% improvement in dorsal skin surface roughness (p < 0.05). Quantitative measurements of hand volume showed a trend toward increased volume for the treated hand, but the difference was not statistically significant.
CONCLUSIONS: We conclude that microneedle fractional radiofrequency is a safe therapeutic option for hand rejuvenation.