Innovative Strategies for Hair Regrowth and Skin Visualization
Abstract
:1. Introduction
2. Structure of the Skin and Hair Follicles
3. Molecular Mechanisms of Hair Regrowth
4. Innovative Strategies for Hair Regrowth
4.1. External Stimulation
4.1.1. Photostimulation
4.1.2. Ultrasound Stimulation
4.1.3. Electrical Stimulation
4.1.4. Stretch Stimulation
4.2. Microneedles for Hair Regrowth
4.3. Regenerative Medicine for Hair Regrowth
4.3.1. Biomimetic Extracellular Matrix
4.3.2. Extracellular Vesicles
4.3.3. Organoid Culture
5. Skin Visualization
6. Claims for Hair Regrowth
7. Natural Products for Hair Regrowth
8. Patent Applications and Clinical Trials for Hair Loss Treatment
Classification | Patent/Application Number | Patent Title | Features | Assignee | Filling Year | Status |
---|---|---|---|---|---|---|
Equipment | CN201711166676.8 [114] | Application of LED-red light with 610 nm–650 nm wavelengths in alopecia treatment | A 610 nm and 650 nm LED red light can effectively prevent hair loss | Harbin Medical University | 2018 | Granted |
CN202010582452.0 [115] | Equipment for laser therapy on androgenetic alopecia and alopecia treatment methods | The laser sterilizes the area of hair loss | Liruiya | 2021 | Granted | |
Regenerative medicine | CN202210069596.5 [113] | A method of HHORSCs exosomes promoting dermal papilla cells to induce hair regeneration | Promotes DPCs to induce hair regrowth | Guangdong LIYI Technology Co. Ltd. | 2022 | Granted |
US17693457 [116] | Methods and compositions for aesthetic and cosmetic treatment and stimulating hair growth | Increases skin volume to prevent or treat hair loss and related diseases | Pluristem Ltd. | 2019 | Granted | |
PCT/IB2021/062226 [117] | Use of miRNA-485 inhibitors for inducing hair regrowth | Increases hair density, follicle density, and hair shaft thickness | Biorchestra Co. Ltd. | 2022 | Granted | |
Drug | US17562976 [118] | Hydrazone amide derivative and application thereof in the preparation of medicaments for preventing and treating alopecia | \ | Shenzhen Cell Inspire Pharmaceutical Dev Co. Ltd. | 2022 | Granted |
Study Title | Medication | ClinicalTrials.gov Identifier | Status | Study Date |
---|---|---|---|---|
ENERGI-F701 for Female Hair Loss Treatment | Drug: ENERGI-F701 | NCT03351322 | Phase 2 | May 2018–December 2019 |
Safety and Efficacy of HST 001 in Male Pattern Hair Loss | Biological: HST 001–0.1 mL X 20 injections | NCT04435847 | Phase 1 | May 2020–January 2021 |
Modulated Light Therapy in Participants With Pattern Hair Loss | Device: REVIAN 101 Device: REVIAN 102 Device: REVIAN 103 Device: REVIAN 100 | NCT04019795 | Phase 3 | January 2017–May 2019 |
Adipose-derived Stem Cell Conditioned Media as a Novel Approach for Hair Regrowth in Male Androgenetic Alopecia | Combination Product: Non-concentrated adipose-derived stem cell conditioned media and 5% Minoxidil Combination Product: Concentrated adipose-derived stem cell conditioned media and 5% Minoxidil Combination Product: Placebo and 5% Minoxidil | NCT05296863 | Phase 3 | October 2021– December 2021 |
Androgenetic Alopecia Treatment Using Varin and Cannabidiol Rich Topical Hemp Oil: A Case Series (Hair Regeneration) | Drug: Hemp Oil | NCT04842383 | Early Phase 1 | April, 2021–October 2021 |
Topical Cetirizine in Androgenetic Alopecia in Females | Topical cetirizine | NCT04481412 | Phase 2 Phase 3 | Ongoing since July 2020 |
A Study Evaluating the Efficacy and Safety of SM04554 Topical Solution in Male Subjects With Androgenetic Alopecia | Topical SM04554 solution | NCT03742518 | Phase 2 Phase 3 | November 2018–December 2021 |
Safety, Tolerability and Pharmacokinetics of KX826 in Healthy Male Subjects With Androgenetic Alopecia Following Topical Single Ascending Dose Administration | KX0826 | NCT04984707 | Phase 1 | January 2019–October 2019 |
Safety and Efficacy Study of Topical DLQ01 in the Treatment of Androgenetic Alopecia (AGA) in Men | Drug: prostaglandin F2a analogue in vehicle solution high dose Drug: prostaglandin F2a analogue in vehicle solution low dose Drug: active ingredient-free vehicle solution to DLQ01 | NCT05636904 | Phase 1 Phase 2 | December 2022–March 2024 |
Topical Cetirizine 1% vs Minoxidil 5% Gel in Treatment of Androgenetic Alopecia | Drug: Cetirizine Drug: Minoxidil | NCT04293822 | Phase 4 | June 2020–November 2021 |
9. Conclusions and Outlook
Funding
Conflicts of Interest
References
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Factors | Molecular of Action | Action Site | Results | Mechanisms | References |
---|---|---|---|---|---|
microRNA | miR122 | Hair follicle | Induces hDPC apoptosis | Repression of IGF1R | [21] |
miR24 | Hair follicle progenitors | miR24 limits the sensitivity of hair follicle progenitors to growth stimuli | Downregulation of PIK3 and CCNE1 | [22] | |
miR218-5p | HFs | Accelerates the onset of anagen | Downregulates SFRP2 to promote β-catenin expression | [23] | |
Hedgehog signaling | Lepr | DPCs | Induces new hair growth and hair multiplication | Downstream SCUBE3-TGF-β signaling | [24] |
mTORC2-Akt signaling | \ | Hair follicle stem cell niche | Allows progenitors to return to the hypoxic niche Resumes the stem cell state | \ | [25] |
Immune system | Glucocorticoids | Treg cells | Facilitates HFSC activation and hair follicle regeneration | GR and Foxp3 cooperatively induce TGF-β3 to activate Smad2/3 in HFSCs | [26] |
Corticosterone | DPCs | Prolongs HFSC quiescence Keeps hair follicles in an extended resting phase | Inhibits Gas6 | [27] | |
Regulatory T cells | HFs | Augments HFSC proliferation and differentiation | Induces high levels of the Notch ligand family member Jagged 1 | [28] | |
Others | Sirt7 | HFSCs | Facilitates the onset of the hair cycle | Promotes NFATc1 degradation | [29] |
Photobiomodulation therapy | β-catenin | HFSCs | Drives quiescent HFSC activation Alleviates hair follicle atrophy | Induces ROS and activates the PI3K/AKT/GSK-3β signaling pathways to inhibit β-catenin degradation | [30] |
Electrical stimulation | \ | HFs | Increases hair follicle number | Improves the secretion of VEGF and KGF | [31] |
Mechanical stretch | \ | HFSCs | Activates stem cells and promotes hair regeneration | M2 macrophages release growth factor HGF and IGF-1 | [32] |
External Stimulation | Mechanisms | Effects | Characteristics/Advantages | Limitations | References |
---|---|---|---|---|---|
Light (Photostimulation) | Increasing the mitochondrial membrane potential Producing ROS to activate cell proliferation and wound healing | Activates the anagen phase and the proliferation of hair follicles | No thermal/inflammatory tissue damage | High energy consumption Large equipment size | [36,37,38] |
Ultrasound | Thermal, cavitation, and acoustic streaming | Delivers drugs into dermal papilla cells | Low cost, non-invasive, good penetration | Thermal damage | [39] |
Electric current | Activating Wnt/β-catenin and MAPK pathways and the secretion of various growth factors | Improves hair follicle density and increases hair shaft length | Low-cost, stable, and small equipment size | Skin damage | [40,41] |
Stretch | Activating Wnt and BPM-2 pathways Recruiting Macrophages and inducing the secretion of various growth factors | Activates hair follicle stem cells | Small equipment size and high compliance | \ | [32,42] |
Imaging Technique | Depth | Principle | Features | Drawbacks | Applications | References |
---|---|---|---|---|---|---|
Optical coherence tomography | <2 mm | Continuous-wave infrared laser radiation | Qualitative Non-invasive | Low resolution, insufficient for observing cell morphology | Vasculature information enables the assessment of inflammatory skin diseases | [81] |
Confocal laser scanning microscopy (CLSM) | 200 μm | \ | Qualitative | Limited to molecules with a fluorophore | Observation of cellular structures | [82] |
Ultrasonography | 10 cm | \ | Qualitative High-resolution | \ | Location of vessels | [83] |
Mass spectrometry imaging (DESI)-MSI | 50–200 µm | Ionization technique | High-throughput Minimum sample preparation Quick results | Lower spatial resolution and sensitivity | Quantitative information Direct analysis of drug distribution Investigation of drug penetration | [84,85] |
RSOM | 1.5–5 mm | Light absorption | Qualitative Non-invasive | Longer scan times | Observation of vascular structures | [86] |
3D OrbiSIMS | 1–2 µm | Collection of secondary ions | Quantitative High-resolution | Can only analyze standard compounds | Examination of endogenous species | [87] |
Herbal Bioactive | Plant Origin | Mechanism of Action | Study Model | Dosage | Conclusions | References |
---|---|---|---|---|---|---|
Tectoridin | Rhizoma belamcandae | Activating Wnt/β-catenin signaling in human dermal papilla cells | Human follicular DPCs/mouse vibrissae organ | Cells: 3, 10, 20, and 50 µM Mouse vibrissae organ: 50 or 100 µM | Tectoridin promoted hair growth in a dose-dependent manner | [90] |
Cepharanthine | Stephania cephalantha | Stimulating the growth of human DPCs (hDPCs), significantly increasing the expression of VEGF and the concentration of intracellular Ca2+, as well as increasing the expression of HIF-1α and HIF-2α and HIF-responsive genes in hDPCs | hDPCs | 0.625/1.25/2.5 μg/mL | Cepharanthine promoted the proliferation of hDPCs and increased the expression of VEGF | [91,92] |
Astragaloside IV | Astragalus membranaceus | Blocking the Fas/Fas L-mediated apoptotic pathway, blocking procaspase-8, and inhibiting caspase-3 and procaspase-9 activities, thus causing the downregulation of Bax and p53, upregulation of Bcl-2 and Bcl-xL, and inhibition of NF-κB and IkB-α phosphorylation, accompanied by a decrease in the levels of three MAPKs: ERK, SAPK/JNK, and p38 | Seven-week-old female C57BL/6 mice (18–20 g) | 1 mM or 100 mM | Astragaloside IV inhibited apoptosis-regression catagen in hair follicles via the Fas/Fas L-mediated cell death pathway, the terminal differentiation of hair keratinocytes, and the levels of regeneration factors and cytokines, leading to hair regeneration. | [93] |
Acankoreoside J | Acanthopanax koreanum | Increasing nuclear β-catenin levels, upregulating cyclin D1, cyclin E, and CDK2, and downregulating p27kip1 in DPCs, thus promoting DPC proliferation | DPCs male Wistar rats (23 days old) | Rat vibrissa dermal papilla cells were treated with acankoreoside J (AK10) at 0.1, 0.2, 1, and 2 µM for 4 days; rat vibrissa follicles were treated with acankoreoside J (AK10) at 0.1, 1, and 10 µM for 21 days | The proliferation of DPCs and the regeneration of hair fibers in rat vibrissa follicles were increased. Hence, acankoreoside J (AK10) might have therapeutic potential for the promotion of hair regeneration | [94] |
3-Deoxysappanchalcone | Caesalpinia sappan L. (Leguminosae) | Stimulating hair regeneration likely by inducing the proliferation of follicular DPCs via the modulation of Wnt/β-catenin and STAT signaling | Human hair follicle DPCs; Seven-week-old female C57BL mice | Two hundred microliters of 3-DSC (3 mM) were applied twice daily for 15 days | The proliferation of HHDPCs and mouse hair regeneration increased in vivo | [95] |
Cedrol | Platycladus orientalis | \ | Six-week-old C57BL/6 mice (body weight 18–20 g) | Different doses (10, 20, 30) mg/mL of cedrol were applied topically to the test area (100 mL) once a day, for 21 days. | Cedrol promoted hair regeneration in a dose-dependent manner | [96,97,98,99] |
Baicalin | Scutellaria baicalensis | Activating Wnt/β catenin signaling, enhancing ALP expression and activity in human DPCs, and increasing the expression of IGF-1 and VEGF | Eight-week-old female C57BL/6 mice | Different doses (50 and 100 μM) in 50% ethanol 1(50 μL) were applied topically every day for approximately 5 weeks | Baicalin promoted hair regeneration by inducing anagen from telogen in mice | [100,101] |
Physcion | Polygonum multiflorum | Inhibiting 5α-reductase | Seven-week-old C57BL/6 mice | 100 μL of Physcion solution (5 mg/mouse/day or 2 mg/mouse/day) for 28 days | Physcion could shorten the time of dorsal skin darkening and hair regeneration, improve hair follicle morphology, and significantly increase hair follicle count | [102] |
Quercetrin | Hottuynia cordata | Activating the MAPK/CREB signaling pathway | hDPCs/mouse vibrissae organ | Cells: 10 and 100 nM, 1 μM Mouse vibrissae organ: 5 and 10 µM | Increased the expression of growth factors such as bFGF, KGF, PDGF-AA, and VEGF, promoting cell proliferation, and increased the phosphorylation of Akt, Erk, and CREB in cultured hDPCs, stimulating hair growth | [103] |
Quercetin | Rutin | Reducing HSP70 levels in skin lesions of mouse models of heat-induced alopecia | Human umbilical vein endothelial cells (HUVECs) and human hair follicle DPCs (HHDPCs) Female C3H/HeJ breeders (approximately 6 months old) | Mice were injected subcutaneously with 100 μL of 10 μM quercetin in 10% dimethyl sulfoxide (DMSO) in phosphate-buffered saline (PBS) once daily for 8 days. Mice were monitored for 6 weeks for hair regeneration. | Quercetin induced hair regeneration in preexisting alopecic lesions in C3H/HeJ mice with spontaneous AA | [104,105,106,107] |
EGCG | Green tea | Downregulating the apoptosis of follicular epithelial cells by upregulating phosphorylated Erk and Akt and increasing the Bcl-2/Bax ratio Androgen metabolism: inhibiting 5a-reductase and repressing the transcription of the androgen receptor (AR) gene | B6CBACF1⁄J female mice (7 weeks old) | Topical application of 100 µL 10% EGCG; T (2 mg/day) was injected intradermally, once daily for 5 days a week, for 12 weeks. The experiment lasted 12 days | EGCG stimulated human hair regeneration through dual proliferative and anti-apoptotic effects on DPCs | [108,109] |
Forsythiaside-A | Forsythia suspensa | Reducing the expression of TGF-β2, caspase-9, and caspase-3 | HHDPCs, human keratinocytes (HaCaTs) | Test group: injected with DHT (30 mg/EA) and orally administered 100 μL of forsythiaside-A (1%) once a day for 35 days | Forsythiaside-A prevented apoptosis, which was induced by DHT and delayed the entry of catagen in androgenic alopecia | [110] |
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Mai, Q.; Han, Y.; Cheng, G.; Ma, R.; Yan, Z.; Chen, X.; Yu, G.; Chen, T.; Zhang, S. Innovative Strategies for Hair Regrowth and Skin Visualization. Pharmaceutics 2023, 15, 1201. https://doi.org/10.3390/pharmaceutics15041201
Mai Q, Han Y, Cheng G, Ma R, Yan Z, Chen X, Yu G, Chen T, Zhang S. Innovative Strategies for Hair Regrowth and Skin Visualization. Pharmaceutics. 2023; 15(4):1201. https://doi.org/10.3390/pharmaceutics15041201
Chicago/Turabian StyleMai, Qiuying, Yanhua Han, Guopan Cheng, Rui Ma, Zhao Yan, Xiaojia Chen, Guangtao Yu, Tongkai Chen, and Shu Zhang. 2023. "Innovative Strategies for Hair Regrowth and Skin Visualization" Pharmaceutics 15, no. 4: 1201. https://doi.org/10.3390/pharmaceutics15041201