Effect of betulin oil on hair growth in hypothyroidism- a long-term blinded pilot study.

BACKGROUND: One common problem in various patient groups is excessive hair loss on the head. One such group is people struggling with hypothyroidism. The market for preparations for hair growth and hair loss prevention includes betulin. PURPOSE: This pilot study investigated its effect on hair loss in hypothyroid patients. STUDY DESIGN: The study included a group of hypothyroid patients and a control group of people without hypothyroidism. Participants were randomly divided into a group taking placebo and betulin. METHODS: Results were investigated using photographic assessment of hair, trichoscopy and subjective evaluation of participants. CONCLUSION: The study did not conclusively prove that betulin would contribute to the inhibition of hair loss or regrowth.

Nanoemulsion with wine lees: a green approach.

Bioactive substances can be found in wine lees, a waste from the winemaking industry. This work developed two formulations, a nanoemulsion with coconut oil (NE-OC) and a nanoemulsion with coconut oil and 0.5% of wine lees extract (NE-OC-Ext), to investigate their effect on untreated, bleached, and bleached-colored hair. The oil-in-water (O/W) nanoemulsions were prepared with coconut oil, TweenTM 80, SpanTM 80, AristoflexTM AVC, Conserve NovaMit MFTM, wine lees extract, and deionized water. The hydration measurements were carried out using a Corneometer® CM 825 with the capacitance method. Scanning electron microscopy (SEM) was used to characterize the effect of formulations on hair fibers. Differential Thermal Analysis (DTA) was to assess the thermal stability and compatibility of wine lees and coconut oil in formulations. Compared to NE-OC, NE-OC-Ext showed a greater hydration effect on bleached-colored hair. DTA showed that NE-OC-Ext presented a smaller number of exothermic degradation events than those of NE-OC, suggesting good interaction and compatibility of the wine lees extract in this formulation. This study highlights the value of wine lees, a residue from the winemaking process, and its possibility of use as raw material for the cosmetic hair industry since it shows a greater moisturizing potential in colored hair.

Promotion of hair growth by a conditioned medium from human umbilical cord mesenchymal stem cells cultivated in a 3D scaffold of gelatin sponge.

BACKGROUND: This study aims to investigate the effects of a conditioned medium (CM) from human umbilical cord mesenchymal stem cells (HuMSCs) cultivated in gelatin sponge (GS-HuMSCs-CM) on hair growth in a mouse model. METHODS: CM was collected from the HuMSCs cultivated in a monolayer or in a gelatin sponge. Vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), keratinocyte growth factor (KGF), and hepatocyte growth factor (HGF) levels in CMs were measured by enzyme-linked immunosorbent assays (ELISAs). A hair loss model by a C57 BL/6J mouse was prepared. The effects of GS-HuMSCs-CM and HuMSCs on hair regrowth in mice were investigated by intradermal injection in the depilated back skin with normal saline (NS) as the control. The time for hair regrowth and full covering in depilated areas was observed, and the hair growth was evaluated histologically and by grossly measuring hair length and diameter. RESULTS: Compared with monolayer cultured cells, the three-dimensional (3D) culture of HuMSCs in gelatin sponge drastically increased VEGF, IGF-1, KGF, and HGF production. GS-HuMSCs-CM and HuMSCs injection both promoted hair regeneration in mice, while GS-HuMSCs-CM presented more enhanced effects in hair length, hair diameter, and growth rate. GS-HuMSCs-CM significantly promoted angiogenesis in injected skin areas, which might also contribute to faster hair regrowth. CONCLUSION: GS-HuMSCs-CM exerted significant effects on inducing hair growth and promoted skin angiogenesis in C57BL/6J mice.

DNA Microarray and Bioinformatic Analysis Reveals the Potential of Whale Oil in Enhancing Hair Growth in a C57BL/6 Mice Dorsal Skin Model.

Much research has been conducted to determine how hair regeneration is regulated, as this could provide therapeutic, cosmetic, and even psychological interventions for hair loss. The current study focused on the hair growth effect and effective utilization of fatty oil obtained from Bryde's whales through a high-throughput DNA microarray approach in conjunction with immunohistochemical observations. The research also examined the mechanisms and factors involved in hair growth. In an experiment using female C57BL/6J mice, the vehicle control group (VC: propylene glycol: ethanol: water), the positive control group (MXD: 3% minoxidil), and the experimental group (WO: 20% whale oil) were topically applied to the dorsal skin of the mouse. The results showed that 3% MXD and 20% WO were more effective than VC in promoting hair growth, especially 20% WO. Furthermore, in hematoxylin and eosin-stained dorsal skin tissue, an increase in the number of hair follicles and subcutaneous tissue thickness was observed with 20% WO. Whole-genome transcriptome analysis also confirmed increases for 20% WO in filaggrin (Flg), a gene related to skin barrier function; fibroblast growth factor 21 (Fgf21), which is involved in hair follicle development; and cysteine-rich secretory protein 1 (Crisp1), a candidate gene for alopecia areata. Furthermore, the results of KEGG pathway analysis indicated that 20% WO may have lower stress and inflammatory responses than 3% MXD. Therefore, WO is expected to be a safe hair growth agent.

Can Plant Extracts Help Prevent Hair Loss or Promote Hair Growth? A Review Comparing Their Therapeutic Efficacies, Phytochemical Components, and Modulatory Targets.

This narrative review aims to examine the therapeutic potential and mechanism of action of plant extracts in preventing and treating alopecia (baldness). We searched and selected research papers on plant extracts related to hair loss, hair growth, or hair regrowth, and comprehensively compared the therapeutic efficacies, phytochemical components, and modulatory targets of plant extracts. These studies showed that various plant extracts increased the survival and proliferation of dermal papilla cells in vitro, enhanced cell proliferation and hair growth in hair follicles ex vivo, and promoted hair growth or regrowth in animal models in vivo. The hair growth-promoting efficacy of several plant extracts was verified in clinical trials. Some phenolic compounds, terpenes and terpenoids, sulfur-containing compounds, and fatty acids were identified as active compounds contained in plant extracts. The pharmacological effects of plant extracts and their active compounds were associated with the promotion of cell survival, cell proliferation, or cell cycle progression, and the upregulation of several growth factors, such as IGF-1, VEGF, HGF, and KGF (FGF-7), leading to the induction and extension of the anagen phase in the hair cycle. Those effects were also associated with the alleviation of oxidative stress, inflammatory response, cellular senescence, or apoptosis, and the downregulation of male hormones and their receptors, preventing the entry into the telogen phase in the hair cycle. Several active plant extracts and phytochemicals stimulated the signaling pathways mediated by protein kinase B (PKB, also called AKT), extracellular signal-regulated kinases (ERK), Wingless and Int-1 (WNT), or sonic hedgehog (SHH), while suppressing other cell signaling pathways mediated by transforming growth factor (TGF)-ß or bone morphogenetic protein (BMP). Thus, well-selected plant extracts and their active compounds can have beneficial effects on hair health. It is proposed that the discovery of phytochemicals targeting the aforementioned cellular events and cell signaling pathways will facilitate the development of new targeted therapies for alopecia.

Polydopamine Synergizes with Quercetin Nanosystem to Reshape the Perifollicular Microenvironment for Accelerating Hair Regrowth in Androgenetic Alopecia.

Accumulated reactive oxygen species (ROS) and their resultant vascular dysfunction in androgenic alopecia (AGA) hinder hair follicle survival and cause permanent hair loss. However, safe and effective strategies to rescue hair follicle viability to enhance AGA therapeutic efficiency remain challenging. Herein, we fabricated a quercetin-encapsulated (Que) and polydopamine-integrated (PDA@QLipo) nanosystem that can reshape the perifollicular microenvironment to initial hair follicle regeneration for AGA treatment. Both the ROS scavenging and angiogenesis promotion abilities of PDA@QLipo were demonstrated. In vivo assays revealed that PDA@QLipo administrated with roller-microneedles successfully rejuvenated the "poor" perifollicular microenvironment, thereby promoting cell proliferation, accelerating hair follicle renewal, and facilitating hair follicle recovery. Moreover, PDA@QLipo achieved a higher hair regeneration coverage of 92.5% in the AGA mouse model than minoxidil (87.8%), even when dosed less frequently. The nanosystem creates a regenerative microenvironment by scavenging ROS and augmenting neovascularity for hair regrowth, presenting a promising approach for AGA clinical treatment.

Minoxidil nanoliposomes as a hair growth stimulator and a scalp disinfectant.

Hair loss (alopecia) continues to be an issue for both sexes. There are multiple ways to reduce the effects of alopecia, one of which is topical minoxidil (MXD). This study aimed to test the effects of minoxidil nanoliposomes (MXD-NLs) on the hair of mice, compared with free MXD and to examine the disinfectant ability of MXD-NLs toward scalp bacteria. To test the study hypothesis, MXD-NLs and free MXD were prepared. Mouse hair was shaved prior to the experiment. MXD-NLs, free MXD and their vehicles were applied for 15 days. In addition, dermal swabs were used to isolate scalp bacteria and test the inhibitory effect of pretreated media with the two formulations and their vehicles. The results revealed that hair growth in the MXD-NLs -treated group (0.65±0.1cm) was higher than that in the free MXD -treated group (0.53±0.2cm). In addition, MXD-NLs treated media reduced the number of scalp bacteria (p=0.0456) compared with free MXD. These results reveal a novel formulation of MXD with faster hair growth properties and a better disinfectant effect than free MXD. This study can help future researchers to expand and develop MXD-NLs.

Reprofiling synthetic glucocorticoid-induced leucine zipper fusion peptide as a novel and effective hair growth promoter.

Hair is a biofilament with unique multi-dimensional values. In human, in addition to physiologic impacts, hair loss and hair related disorders can affect characteristic features, emotions, and social behaviors. Despite significant advancement, there is a dire need to explore alternative novel therapies with higher efficacy, less side effects and lower cost to promote hair growth to treat hair deficiency. Glucocorticoid-induced leucine zipper (GILZ) is a protein rapidly induced by glucocorticoids. Studies from our group and many others have suggested that a synthetic form of GILZ, TAT-GILZ, a fusion peptide of trans-activator of transcription and GILZ, can function as a potent regulator of inflammatory responses, re-establishing and maintaining the homeostasis. In this study, we investigate whether TAT-GILZ could promote and contribute to hair growth. For our pre-clinical model, we used 9-12 week-old male BALB/c and nude (athymic, nu/J) mice. We applied TAT-GILZ and/or TAT (vehicle) intradermally to depilated/hairless mice. Direct observation, histological examination, and Immunofluorescence imaging were used to assess the effects and compare different treatments. In addition, we tested two current treatment for hair loss/growth, finasteride and minoxidil, for optimal evaluation of TAT-GILZ in a comparative fashion. Our results showed, for the first time, that synthetic TAT-GILZ peptide accelerated hair growth on depilated dorsal skin of BALB/c and induced hair on the skin of athymic mice where hair growth was not expected. In addition, TAT-GILZ was able to enhance hair follicle stem cells and re-established the homeostasis by increasing counter inflammatory signals including higher regulatory T cells and glucocorticoid receptors. In conclusion, our novel findings suggest that reprofiling synthetic TAT-GILZ peptide could promote hair growth by increasing hair follicle stem cells and re-establishing homeostasis.

Hair growth-promoting effects of Enz_MoriL on human dermal papilla cells through modulation of the Wnt/ß-Catenin and JAK-STAT signaling pathways.

Enz_MoriL is a naturally occurring substance extracted from the leaves of Morus alba L. through enzymatic conversion. Historically, M. alba L. has been recognized for its potential to promote hair regrowth. However, the precise mechanism by which Enz_MoriL affects human hair follicle dermal papilla cells (hDPCs) remains unclear. The aim of this study was to investigate the molecular basis of Enz_MoriL's effect on hair growth in hDPCs. Interferon-gamma (IFN-γ) was used to examine the effects of Enz_MoriL on hDPCs during the anagen and catagen phases, as well as under conditions mimicking alopecia areata (AA). Enz_MoriL demonstrated the ability to promote cell proliferation in both anagen and catagen stages. It increased the levels of active ß-catenin in the catagen stage induced by IFN-γ, leading to its nuclear translocation. This effect was achieved by increasing the phosphorylation of GSK3ß and decreasing the expression of DKK-1. This stimulation induced proliferation in hDPCs and upregulated the expression of the Wnt family members 3a, 5a, and 7a at the transcript level. Additionally, Enz_MoriL suppressed JAK1 and STAT3 phosphorylation, contrasting with IFN-γ, which induced them in the catagen stage. In conclusion, Enz_MoriL directly induced signals for anagen re-entry into hDPCs by affecting the Wnt/ß-catenin pathway and enhancing the production of growth factors. Furthermore, Enz_MoriL attenuated and reversed the interferon-induced AA-like environment by blocking the JAK-STAT pathway in hDPCs.

Ellagic acid inhibits dihydrotestosterone-induced ferroptosis and promotes hair regeneration by activating the wnt/ß-catenin signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Androgenic alopecia (AGA) is the most prevalent form of hair loss in clinical practice and affects the physical and psychological well-being of adolescents. Paeonia lactiflora Pallas (PL), which is widely used in traditional Chinese medicine, enhances blood function and promotes hair growth, and ellagic acid (EA), a polyphenol in PL extract, shows strong antioxidant, anti-aging, and anti-inflammatory properties and also plays a role in the treatment of various skin conditions. However, its role and mechanism of action in AGA remain unclear. AIM OF THE STUDY: To determine whether EA can rescue slow hair regeneration by regulating dihydrotestosterone (DHT)-induced ferroptosis in AGA mice and clarify the effect of EA on DHT-induced ferroptosis in dermal papilla cells (DPCs). MATERIALS AND METHODS: Male C57BL/6 mice were used to establish a DHT-induced AGA mouse model, whereas DPCs were used to establish a DHT-induced cellular model. Thereafter, we investigated the therapeutic mechanism of action of EA via immunofluorescence, western blot analysis, immunohistochemistry, electron microscopy, and molecular docking. RESULTS: EA stimulated hair regeneration in mice and reversed DHT-induced increases in iron content, lipid peroxidation, and DHT-induced mitochondrial dysfunction by activating the Wnt/ß-catenin signaling pathway. Further, ß-catenin knockdown suppressed the inhibitory effect of EA on DHT-induced ferroptosis in DPCs. CONCLUSION: EA inhibits DHT-induced ferroptosis and promotes hair regrowth in mice by activating the Wnt/ß-catenin signaling pathway. Thus, it has potential for use as a treatment option for AGA.

Transient stimulation of TRPMLs enhance the functionality of hDPCs and facilitate hair growth in mice.

Autophagy is essential for eliminating aging and organelle damage that maintaining cellular homeostasis. However, the dysfunction of autophagy has been proven in hair loss such as AGA. Despite the crucial role of TRPML channels in regulating autophagy, their specific function in hair growth remains unclarified. To investigate the biological functions and associated molecular mechanisms of TRPMLs in hair growth, Animal experiments were conducted to confirm the function of TRLMLs activation in promoting hair growth. Subsequently, we analyzed molecular mechanisms in human dermal papilla cells (hDPCs) activated by TRPMLs through transcriptome sequencing analysis. MLSA1(a TRPML agonist) promoted hair regeneration and accelerated hair cycle transition in mice. The activation of TRPMLs upregulated calcium signaling inducing hDPCs to secrete hair growth promoting factors and decrease hair growth inhibiting factors. In addition, activation of TRPMLs triggered autophagy and reduced the generation of ROS, thereby delaying the senescence of hDPCs. All these findings suggested that TRPMLs activation could promote hair growth by regulating hDPCs secretion of hair growth-related factors. Moreover, it may play a prominent role in preventing hDPCs from ROS damage induced by H2O2 or DHT. Targeting TRPMLs may represent a promising therapeutic strategy for treating hair loss.

Pilose antler extract promotes hair growth in androgenic alopecia mice by promoting the initial anagen phase.

Androgenetic alopecia (AGA) is a prevalent disease in worldwide, local application or oral are often used to treat AGA, however, effective treatments for AGA are currently limited. In this work, we observed the promoting the initial anagen phase effect of pilose antler extract (PAE) on hair regeneration in AGA mice. We found that PAE accelerated hair growth and increased the degree of skin blackness by non-invasive in vivo methods including camera, optical coherence tomography and dermoscopy. Meanwhile, HE staining of sagittal and coronal skin sections revealed that PAE augmented the quantity and length of hair follicles, while also enhancing skin thickness and hair papilla diameter. Furthermore, PAE facilitated the shift of the growth cycle from the telogen to the anagen phase and expedited the proliferation of hair follicle stem cells and matrix cells in mice with AGA. This acceleration enabled the hair follicles to enter the growth phase at an earlier stage. PAE upregulated the expression of the sonic hedgehog (SHH), smoothened receptor, glioma-associated hemolog1 (GLI1), and downregulated the expression of bone morphogenetic protein 4 (BMP4), recombinant mothers against decapentaplegic homolog (Smad) 1 and 5 phosphorylation. This evidence suggests that PAE fosters hair growth and facilitates the transition of the growth cycle from the telogen to the anagen phase in AGA mice. This effect is achieved by enhancing the proliferation of follicle stem cells and matrix cells through the activation of the SHH/GLI pathway and suppression of the BMP/Smad pathway.

Materiobiomodulated ROS Therapy for De Novo Hair Growth.

Hair loss is characterized by the inability of hair follicles (HFs) to enter the telogen-anagen transition (TAT) and lack of de novo HFs. Current pharmaceutical therapies and surgical modalities have been largely limited to regulating hair regrowth efficiently without side effects and lacking treatment compliance. Here, this work proposes a materiobiomodulation therapy (MBMT), wherein polydopamine (PDA) nanoparticles with redox activity can be modulated to have a stoichiometric ROS (H2O2) donating ability. These nanoparticles can intracellularly deliver ROS with high-efficiency via the clathrin-dependent endocytosis process. Utilizing homozygote transgenic HyPerion (a genetically-encoded H2O2 biosensor) mice, this work also achieves in vivo dynamic monitoring of intracellular H2O2 elevation induced by ROS donators. Subcutaneous administration with ROS donators results in rapid onset of TAT and subsequent hair regrowth with a specific ROS "hormesis effect." Mechanistically, ROS activate ß-catenin-dependent Wnt signaling, upregulating hair follicle stem cell expression. This work further develops a microneedles patch for transdermal ROS delivery, demonstrating long-term, low-dose ROS release. Unlike photobiomodulation therapy (PBMT), MBMT requires no external stimuli, providing a convenient and efficient approach for clinical hair loss treatment. This material-HF communication implicates new avenues in HF-related diseases, achieving targeted ROS delivery with minimal side effects.

The role of fractional laser-assisted drug delivery in enhancing the efficacy of topical bimatoprost solution in the treatment of alopecia areata: An intra-patient comparative randomized clinical trial.

BACKGROUND: Transepidermal drug delivery is a novel therapeutic technique to boost efficacy of topical drugs. AIM: In this clinical trial we evaluate the efficacy of the combination of fractional carbon dioxide (FCO2) laser and bimatoprost solution compared to bimatoprost alone in the treatment of alopecia areata. METHODS: This is a prospective intra-patient comparative randomized clinical trial on 20 patients with alopecia areata. In each participant two patches were chosen to randomly receive either topical 0.03% bimatoprost solution (twice a day for 12 weeks) alone or in combination with FCO2 laser (every 2 weeks for 12 weeks). Then response to treatment was evaluated by the measurement of the severity of alopecia tool score system (SALT) score, percentage of hair regrowth, physician assessment and patients' satisfaction. RESULTS: SALT score was reduced significantly during treatment sessions and after a 3-month follow-up in both treatment groups (p = 0.000). The mean percentage of improvement in SALT score in the combination therapy and monotherapy groups were 46.43 ± 4.35% and 21.16 ± 4.06% at the end of the study and 46.42 ± 5.75% and16.11 ± 3.10% at the end of the follow-up period, respectively (p = 0.000). A general linear model of two-way analysis demonstrated a significantly superior outcome in the combination therapy group compared to the monotherapy group during time (F1.6, 13.2 = 43.8. p = 0.000). CONCLUSION: Fractional ablative laser can be considered as an assistant method for enhancing of efficacy of topical drugs especially in refractory cases of patchy alopecia areata.

In Vitro and In Vivo Models for the Development of Hair Growth Materials By Regulating the ß-Catenin Signaling Pathways.

Although hair loss contributes to various social and economic, research methods for material development are currently limited. In this study, we established a research model for developing materials for hair growth through the regulation of ß-catenin. We confirmed that 100 nM tegatrabetan (TG), a ß-catenin inhibitor, decreased the proliferation of human hair follicle dermal papilla cells (HFDPCs) at 72 h. In addition, TG-induced apoptosis suppressed the phosphorylation of GSK-3ß and Akt, translocation of ß-catenin from the cytosol to the nucleus, and the expression of cyclin D1. Interestingly, TG significantly increased the G2/M arrest in HFDPCs. Subcutaneous injection of TG suppressed hair growth and the number of hair follicles in C57BL/6 mice. Moreover, TG inhibited the expression of cyclin D1, ß-catenin, keratin 14, and Ki67. These results suggest that TG-induced inhibition of hair growth can be a promising model for developing new materials for enhancing ß-catenin-mediated hair growth.

Preparation and in vitro evaluation of protective effects of Silibinin-loaded polymeric micelles on human hair against UV-B radiation.

BACKGROUND: The purpose of this study was to investigate the protective effect of Silibinin-loaded polymeric micelles from human hair against UV-B radiation. METHODS: Eight formulations with different concentrations of Silibinin, Pluronic F-127, and Labrasol-Labrafil were made by a solvent evaporation method, and the selected formulation was chosen by examining their properties like particle size and loading efficiency. Six groups of human hair, including a group that received the selected formulation, were exposed to UV-B radiation and by calculating its factors such as peak-to-valley roughness, RMS roughness, FTIR, and the amount of protein loss, the protective effect of the selected formulation was judged. RESULTS: According to the results, the loading efficiency and particle size of the selected formulation were 45.34% and 43.19 nm. The Silibinin release profile had two parts, fast and slow, which were suitable for creating a drug depot on hair. Its zeta potential also confirmed the minimum electrostatic interference between the formulation and hair surface. The zeta potential of selected formulation was -5.9 mv. Examination of AFM images showed that the selected formulation was able to prevent the increase in peak-to-valley roughness and RMS roughness caused by UV-B radiation. RMS roughness after 600 h of UV radiation in Groups 5 and 6 was significantly lower than the negative control group and the amount of this factor did not differ significantly between 0 and 600, so it can be concluded that the selected formulation containing Silibinin and the positive control group was able to prevent the increase of RMS roughness and hair destruction. In other hands, the two positive control groups and the selected formulation containing Silibinin were able to effectively reduce hair protein loss. CONCLUSION: Silibinin-loaded polymeric micelles were able to effectively protect hair from structural and chemical changes caused by UV-B radiation.

Investigator-blinded, controlled, and randomized comparative study on 1565 nm non-ablative fractional laser versus 5% minoxidil for treatment of androgenetic alopecia.

BACKGROUND: Characterized by progressive hair loss due to an excessive response to androgens, androgenetic alopecia (AGA) affects up to 50% of males and females. Minoxidil is one of approved medications for AGA but inadequate responses occur in many patients. AIMS: To determine whether 1565 nm non-ablative fractional laser (NAFL) could yield better therapeutic benefits for patients with AGA as compared with 5% minoxidil. METHODS: Thirty patients with AGA were enrolled; they were randomly assigned into the laser or minoxidil treatment groups. For the laser treatment group, patients were treated by 1565 nm NAFL at 10 mJ, 250 spots/cm2 with 2 weeks intervals for 4 sessions in total. For the minoxidil treatment group, 1-milliliter of topical 5% minoxidil solution was applied to hair loss area twice a day. RESULTS: The primary outcomes were the changes in numerous hair growth indexes at the Week 10 as compared with the baselines. Both 1565 nm NAFL and 5% minoxidil led to significantly greater hair densities and diameters in patients at the Week 10 than the baselines (p < 0.01). As compared with 5% minoxidil, 1565 nm NAFL showed significantly greater improvements in total hair number, total hair density (hair/cm2), terminal hair number, terminal hair density (hair/cm2), number of hair follicle units, and average hair number/number of hair follicle units. CONCLUSIONS: Our data demonstrate that 1565 nm NAFL exhibits superior clinical efficacy in some aspects of hair growth to the topical minoxidil. It is a safe and effective modality in treating AGA.

Combined microneedling with topical vitamin D3 or bimatoprost versus microneedling alone in the treatment of alopecia areata: A comparative randomized trial.

INTRODUCTION: Alopecia areata (AA) is a challenging disease with variable treatment outcomes. Hair follicles express vitamin D receptors. Therefore, vitamin D3 may be promising for AA treatment through immunomodulatory mechanisms. The efficacy of bimatoprost in scalp AA treatment was reported by few studies. OBJECTIVE: To evaluate the efficacy and safety of microneedling (MN) with topical vitamin D3 versus MN with bimatoprost in comparison with MN alone in the treatment of localized AA. PATIENTS AND METHODS: Seventy-five patients with localized AA were divided into three groups. The first group: 25 patients were treated with MN alone. The second group: 25 patients treated with MN combined with topical vitamin D3. The third group: 25 patients treated with MN combined with bimatoprost solution. The response was evaluated clinically and dermoscopically. RESULTS: At the end of the study, all groups showed a statistically significant decrease in the SALT score compared to the baseline. The clinical response (regrowth scale): vitamin D and bimatoprost groups showed a statistically significant higher regrowth scale compared to MN alone group (p-value = 0.000). After treatment, hair regrowth was significantly higher in MN combined with bimatoprost than in MN combined with topical vitamin D3. However, after 3 months of follow-up, there was no statistically significant difference between both groups. Side effects were mild and transient in all groups. CONCLUSION: Topical vitamin D3 and bimatoprost combined with MN are safe and effective therapeutic options for localized AA.