Microneedle-mediated therapies in hair loss: applications, mechanisms, and future directions

Abstract

Microneedles, as minimally invasive tools for percutaneous delivery, have undergone significant technological advancements over the past decade, greatly expanding their application in the treatment of hair loss. Traditional microneedle devices promote hair regrowth by stimulating vascularization and the release of growth factors through controlled skin disruption. In addition, microneedle-mediated drug delivery enhances local drug penetration and absorption, thereby regulating the hair growth cycle more effectively. During hair transplantation procedures, microneedle-assisted techniques can notably improve follicle survival rates due to their precision and advanced design. For individuals with baldness, tissue-engineered hair follicle regeneration offers an innovative and effective strategy to increase the total number of hair follicles. However, these engineered follicles often face challenges, such as difficulty in emerging through the skin and growing in excessively dense or disorganized patterns. Integrating microneedle arrays with tissue engineering approaches may help address these issues by enabling better control over the direction and density of regenerated hair. This article reviews the historical development of microneedles, examines their current applications in hair loss therapy, and discusses ongoing challenges in the field. The goal is to explore the therapeutic potential of microneedles in hair regeneration and to offer insights that may guide future treatment strategies.

Keywords

Microneedles / hair loss / hair regeneration / drug delivery

References

[1] Bhatnagar S,Venuganti VVK.Microneedles in the clinic.J Control Release2017;260:164-82

[2] Ma Y,Li M,Yan Z.An antimicrobial microneedle patch promotes functional healing of infected wounds through controlled release of adipose tissue-derived apoptotic vesicles.J Nanobiotechnology2024;22:579 PMCID:PMC11414280

[3] Sartawi Z,Faisal W.Dissolving microneedles: applications and growing therapeutic potential.J Control Release2022;348:186-205

[4] Han Y,Lin W.Microneedle-based approaches for skin disease treatment.Nanomicro Lett2025;17:132 PMCID:PMC11799520

[5] Wu C,Huang C,Zhang L.Microneedles as transdermal drug delivery system for enhancing skin disease treatment.Acta Pharm Sin B2024;14:5161-80 PMCID:PMC11725105

[6] Mubki T,Olszewska M.Evaluation and diagnosis of the hair loss patient: part I. History and clinical examination.J Am Acad Dermatol2014;71:415.e1-15

[7] Fertig RM,Cervantes J.Microneedling for the treatment of hair loss?.J Eur Acad Dermatol Venereol2018;32:564-9

[8] Gupta AK,Venkataraman M.Microneedling for hair loss.J Cosmet Dermatol2022;21:108-17

[9] Chen Y,Wu W.Gas-propelled anti-hair follicle aging microneedle patch for the treatment of androgenetic alopecia.J Control Release2025;379:636-51

[10] Lee SJ,Hwang SJ.Evaluation of survival rate after follicular unit transplantation using the KNU implanter.Dermatol Surg2001;27:716-20

[11] Kageyama T,Shimizu A,Fukuda J.Preparation of hair beads and hair follicle germs for regenerative medicine.Biomaterials2019;212:55-63

[12] He C,Zhou H.Magnetic nanoactuator-protein fiber coated hydrogel dressing for well-balanced skin wound healing and tissue regeneration.ACS Nano2025;19:1713-31

[13] Chambers R.Microdissection studies, III. Some problems in the maturation and fertilization of the echinoderm egg.Biology Bulletin1921;41:318-50

[14] Gerstel Martin S, Place Virgil A. Drug delivery device. US 3964482 A, 1976.

[15] Hashmi S,Hashmi G,Gaugler R.Genetic transformation of nematodes using arrays of micromechanical piercing structures.Biotechniques1995;19:766-70

[16] Henry S,Allen MG.Microfabricated microneedles: a novel approach to transdermal drug delivery.J Pharm Sci1998;87:922-5

[17] Matriano JA,Johnson J.Macroflux microprojection array patch technology: a new and efficient approach for intracutaneous immunization.Pharm Res2002;19:63-70

[18] McAllister DV,Davis SP.Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies.Proc Natl Acad Sci U S A2003;100:13755-60 PMCID:PMC283494

[19] Miyano T,Kanno T.Sugar micro needles as transdermic drug delivery system.Biomed Microdevices2005;7:185-8

[20] Kim M,Park JH.Hydrogel swelling as a trigger to release biodegradable polymer microneedles in skin.Biomaterials2012;33:668-78

[21] Wang J,Yu J.Core-shell microneedle gel for self-regulated insulin delivery.ACS Nano2018;12:2466-73 PMCID:PMC6037424

[22] Chang H,Zheng M.Cryomicroneedles for transdermal cell delivery.Nat Biomed Eng2021;5:1008-18

[23] Zheng B,Feng S.Organoid-loaded cryomicroneedles for biomimic hair regeneration.Adv Funct Mater2024;34:2304950

[24] Li WZ,Zhou JP.Super-short solid silicon microneedles for transdermal drug delivery applications.Int J Pharm2010;389:122-9

[25] Li J,Zhou Y.Fabrication of a Ti porous microneedle array by metal injection molding for transdermal drug delivery.PLoS One2017;12:e0172043 PMCID:PMC5302820

[26] Cormier M,Ameri M.Transdermal delivery of desmopressin using a coated microneedle array patch system.J Control Release2004;97:503-11

[27] Boks MA,Engels S,Kooyk Yv.Controlled release of a model vaccine by nanoporous ceramic microneedle arrays.Int J Pharm2015;491:375-83

[28] Wang PM,Prausnitz MR.Minimally invasive extraction of dermal interstitial fluid for glucose monitoring using microneedles.Diabetes Technol Ther2005;7:131-41

[29] Prausnitz MR.Microneedles for transdermal drug delivery.Adv Drug Deliv Rev2004;56:581-7

[30] Larrañeta E,Woolfson AD.Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development.Mater Sci Eng R Rep2016;104:1-32

[31] Nguyen TT,Kim JS.Skin immunization with third-generation hepatitis B surface antigen using microneedles.Vaccine2019;37:5954-61

[32] Kim MJ,Kim DS.Minoxidil-loaded hyaluronic acid dissolving microneedles to alleviate hair loss in an alopecia animal model.Acta Biomater2022;143:189-202

[33] Zeng Y,Jiang X.Self-assembled hyaluronic acid nanoparticles delivered by polymeric microneedles for targeted and long-acting therapy of psoriasis.Int J Pharm2025;669:125073

[34] Oh JH,Do KY.Influence of the delivery systems using a microneedle array on the permeation of a hydrophilic molecule, calcein.Eur J Pharm Biopharm2008;69:1040-5

[35] Mohite P,Munde S.Hydrogel-forming microneedles in the management of dermal disorders through a non-invasive process: a review.Gels2024;10:719 PMCID:PMC11594199

[36] Xu B,Yang G,Zhou Z.Novel double-layered PLGA microparticles-dissolving microneedle (MPs-DMN) system for peptide drugs sustained release by transdermal delivery.Int J Pharm2025;670:125128

[37] Wang QL,Chen BZ.Dissolvable layered microneedles with core-shell structures for transdermal drug delivery.Mater Sci Eng C Mater Biol Appl2018;83:143-7

[38] You SK,Park HH.Effect of applying modes of the polymer microneedle-roller on the permeation of L-ascorbic acid in rats.J Drug Target2010;18:15-20

[39] Dhurat R,Avhad G,Pal A.A randomized evaluator blinded study of effect of microneedling in androgenetic alopecia: a pilot study.Int J Trichology2013;5:6-11 PMCID:PMC3746236

[40] Lee YB,Lee JH.Effects of topical application of growth factors followed by microneedle therapy in women with female pattern hair loss: a pilot study.J Dermatol2013;40:81-3

[41] Zhang F,Feng JD.Observation on the efficacy of a combined treatment for moderate and severe androgenetic alopecia incorporating electric microneedles.Clin Cosmet Investig Dermatol2022;15:2573-81 PMCID:PMC9719273

[42] Yu AJ,Xu XG.A pilot split-scalp study of combined fractional radiofrequency microneedling and 5% topical minoxidil in treating male pattern hair loss.Clin Exp Dermatol2018;43:775-81

[43] Thepphankulngarm N,Hirun N.Nanotechnology-driven delivery of caffeine using ultradeformable liposomes-coated hollow mesoporous silica nanoparticles for enhanced follicular delivery and treatment of androgenetic alopecia.Int J Mol Sci2024;25:12170 PMCID:PMC11595114

[44] Kim S,Yang H.Transdermal finasteride delivery via powder-carrying microneedles with a diffusion enhancer to treat androgenetic alopecia.J Control Release2019;316:1-11

[45] Prabahar K,Elsherbiny N.Microneedle mediated transdermal delivery of β-sitosterol loaded nanostructured lipid nanoparticles for androgenic alopecia.Drug Deliv2022;29:3022-34 PMCID:PMC10003132

[46] Messenger AG.Minoxidil: mechanisms of action on hair growth.Br J Dermatol2004;150:186-94

[47] Duvic M,Valero V.A randomized trial of minoxidil in chemotherapy-induced alopecia.J Am Acad Dermatol1996;35:74-8

[48] Chen H,Huang Y.Remodel the perifollicular microenvironment via Minoxidil-loaded microneedle patch and cold atmospheric plasma for treating androgenetic alopecia.Nano Res2024;17:6411-9

[49] Chew EGY,Bahta AW.Differential expression between human dermal papilla cells from balding and non-balding scalps reveals new candidate genes for androgenetic alopecia.J Invest Dermatol2016;136:1559-67

[50] Wang R,Bian Q.PROTAC degraders of androgen receptor-integrated dissolving microneedles for androgenetic alopecia and recrudescence treatment via single topical administration.Small Methods2023;7:e2201293

[51] Ragab SEM,Morad HA.Platelet-rich plasma in alopecia areata: intradermal injection versus topical application with transepidermal delivery via either fractional carbon dioxide laser or microneedling.Acta Dermatovenerol Alp Pannonica Adriat2020;29:169-73

[52] Chandrashekar B,Mysore V.Alopecia areata-successful outcome with microneedling and triamcinolone acetonide.J Cutan Aesthet Surg2014;7:63-4 PMCID:PMC3996798

[53] Jadkauskaite L,Schäfer M,Paus R.Oxidative stress management in the hair follicle: Could targeting NRF2 counter age-related hair disorders and beyond?.Bioessays2017;39:1700029

[54] Wu H,Wang S.Ceria nanocrystals decorated mesoporous silica nanoparticle based ROS-scavenging tissue adhesive for highly efficient regenerative wound healing.Biomaterials2018;151:66-77

[55] Yuan A,Bian Q.Ceria nanozyme-integrated microneedles reshape the perifollicular microenvironment for androgenetic alopecia treatment.ACS Nano2021;15:13759-69

[56] Forman HJ.Targeting oxidative stress in disease: promise and limitations of antioxidant therapy.Nat Rev Drug Discov2021;20:652 PMCID:PMC8414784

[57] Han Y,Wang L.Machine-learning-driven synthesis of carbon dots with enhanced quantum yields.ACS Nano2020;14:14761-8

[58] Frey NC,Jariwala D.Machine learning-enabled design of point defects in 2D materials for quantum and neuromorphic information processing.ACS Nano2020;14:13406-17

[59] Zhang C,Shi S.Machine learning guided discovery of superoxide dismutase nanozymes for androgenetic alopecia.Nano Lett2022;22:8592-600

[60] Jo SJ,Yoon SY.Valproic acid promotes human hair growth in in vitro culture model.J Dermatol Sci2013;72:16-24

[61] Lee SH,Shin SH.Valproic acid induces hair regeneration in murine model and activates alkaline phosphatase activity in human dermal papilla cells.PLoS One2012;7:e34152 PMCID:PMC3323655

[62] Fakhraei Lahiji S,Kim S.Transcutaneous implantation of valproic acid-encapsulated dissolving microneedles induces hair regrowth.Biomaterials2018;167:69-79

[63] Hartman N,Fabi S.Update on exosomes in aesthetics.Dermatol Surg2022;48:862-5

[64] Gross JC,Bartscherer K.Active Wnt proteins are secreted on exosomes.Nat Cell Biol2012;14:1036-45

[65] Kost Y,Mhaimeed N,Kobets K.Exosome therapy in hair regeneration: a literature review of the evidence, challenges, and future opportunities.J Cosmet Dermatol2022;21:3226-31

[66] Flores A,Krall AS.Lactate dehydrogenase activity drives hair follicle stem cell activation.Nat Cell Biol2017;19:1017-26 PMCID:PMC5657543

[67] Yang G,Wen D.A therapeutic microneedle patch made from hair-derived keratin for promoting hair regrowth.ACS Nano2019;13:4354-60

[68] Chai M,Vergnes L.Stimulation of hair growth by small molecules that activate autophagy.Cell Rep2019;27:3413-21.e3

[69] Kwon OS,Yoo HG.Human hair growth enhancement in vitro by green tea epigallocatechin-3-gallate (EGCG).Phytomedicine2007;14:551-5

[70] Lin Y,Xiao T.Promotion of hair regrowth by transdermal dissolvable microneedles loaded with rapamycin and epigallocatechin gallate nanoparticles.Pharmaceutics2022;14:1404 PMCID:PMC9318735

[71] Zhao Y,Ye W.A lipid-polymer hybrid nanoparticle (LPN)-loaded dissolving microneedle patch for promoting hair regrowth by transdermal miR-218 delivery.Biomater Sci2022;11:140-52

[72] Almohanna HM,Tsatalis JP.The role of vitamins and minerals in hair loss: a review.Dermatol Ther2019;9:51-70 PMCID:PMC6380979

[73] Finner AM.Nutrition and hair: deficiencies and supplements.Dermatol Clin2013;31:167-72

[74] Zhang Y,Bao F.Multifunctional Zn doped hollow mesoporous silica/polycaprolactone electrospun membranes with enhanced hair follicle regeneration and antibacterial activity for wound healing.Nanoscale2019;11:6315-33

[75] Wu C,Xu M.Copper-containing mesoporous bioactive glass scaffolds with multifunctional properties of angiogenesis capacity, osteostimulation and antibacterial activity.Biomaterials2013;34:422-33

[76] Sugimoto Y,Labrie F.Cations inhibit specifically type I 5 alpha-reductase found in human skin.J Invest Dermatol1995;104:775-8

[77] Kasprzak MM,Ochocki J.Properties and applications of flavonoid metal complexes.RSC Adv2015;5:45853-77

[78] Zhang Z,Chang D.A combination therapy for androgenic alopecia based on quercetin and zinc/copper dual-doped mesoporous silica nanocomposite microneedle patch.Bioact Mater2023;24:81-95 PMCID:PMC9772573

[79] Rajendran RL,Bak SS.Extracellular vesicles derived from MSCs activates dermal papilla cell in vitro and promotes hair follicle conversion from telogen to anagen in mice.Sci Rep2017;7:15560 PMCID:PMC5686117

[80] Lee K,Lee J.A patch of detachable hybrid microneedle depot for localized delivery of mesenchymal stem cells in regeneration therapy.Adv Funct Mater2020;30:2000086 PMCID:PMC7567343

[81] Fukuoka H,Suga H.Hair regeneration therapy: application of adipose-derived stem cells.Curr Stem Cell Res Ther2017;12:531-4 PMCID:PMC6327114

[82] Liu Y,Wang J.Exosomes as a novel pathway for regulating development and diseases of the skin.Biomed Rep2018;8:207-14 PMCID:PMC5867470

[83] Shi Y,Li H.A drug-free, hair follicle cycling regulatable, separable, antibacterial microneedle patch for hair regeneration therapy.Adv Healthc Mater2022;11:e2200908

[84] Rassman WR,Kim J.Scalp micropigmentation: a useful treatment for hair loss.Facial Plast Surg Clin North Am2013;21:497-503

[85] Lahiji SF,Kim Y,Yang H.Scalp micro-pigmentation via transcutaneous implantation of flexible tissue interlocking biodegradable microneedles.Pharmaceutics2019;11:549 PMCID:PMC6920983

[86] Plikus MV,de la Cruz D.Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration.Nature2008;451:340-4 PMCID:PMC2696201

[87] Paus R.The biology of hair follicles.N Engl J Med1999;341:491-7

[88] Chang LY,Jablonski NG.Evolution of long scalp hair in humans.Br J Dermatol2025;192:574-84 PMCID:PMC11918595

[89] Botchkarev VA,Nakamura M.Noggin is required for induction of the hair follicle growth phase in postnatal skin.FASEB J2001;15:2205-14

[90] Chen D,Guo C,Atit R.Dermal β-catenin activity in response to epidermal Wnt ligands is required for fibroblast proliferation and hair follicle initiation.Development2012;139:1522-33 PMCID:PMC3308184

[91] Huelsken J,Erdmann B,Birchmeier W.β-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin.Cell2001;105:533-45

[92] Kulessa H,Hogan BL.Inhibition of Bmp signaling affects growth and differentiation in the anagen hair follicle.EMBO J2000;19:6664-74 PMCID:PMC305899

[93] Botchkarev VA,Roth W.Noggin is a mesenchymally derived stimulator of hair-follicle induction.Nat Cell Biol1999;1:158-64

[94] Wang LC,Gambardella L.Regular articles: conditional disruption of hedgehog signaling pathway defines its critical role in hair development and regeneration.J Invest Dermatol2000;114:901-8

[95] Blanpain C,Geoghegan A,Fuchs E.Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche.Cell2004;118:635-48

[96] Genander M,Ramsköld D.BMP signaling and its pSMAD1/5 target genes differentially regulate hair follicle stem cell lineages.Cell Stem Cell2014;15:619-33 PMCID:PMC4276600

[97] Yano K,Detmar M.Control of hair growth and follicle size by VEGF-mediated angiogenesis.J Clin Invest2001;107:409-17 PMCID:PMC199257

[98] Chen Y,Feng J.Novel recombinant R-spondin1 promotes hair regeneration by targeting the Wnt/β-catenin signaling pathway.Acta Biochim Biophys Sin2023;55:1213-21 PMCID:PMC10448039

[99] Kim YS,Kim JE,Kim BJ.Repeated microneedle stimulation induces enhanced hair growth in a murine model.Ann Dermatol2016;28:586-92 PMCID:PMC5064188

[100] Ocampo-Garza SS,Ocampo-Candiani J,Villani A.Micro needling: a novel therapeutic approach for androgenetic alopecia, a review of literature.Dermatol Ther2020;33:e14267

[101] Xing Z,Zhao C.Microenvironment-responsive recombinant collagen XVII-based composite microneedles for the treatment of androgenetic alopecia.Acta Biomater2025;200:400-15

[102] Jimenez F,Vogel JE.Hair transplantation: basic overview.J Am Acad Dermatol2021;85:803-14

[103] Sharma R.Follicular unit extraction (FUE) hair transplant: curves ahead.J Maxillofac Oral Surg2019;18:509-17 PMCID:PMC6795649

[104] Krefft-Trzciniecka K,Pakiet A,Szepietowski JC.Short-term clinical assessment of treating female androgenetic alopecia with autologous stem cells derived from human hair follicles.Biomedicines2024;12:153 PMCID:PMC10813176

[105] Gentile P,Perego F.Autologous micrografts containing nanovesicles, exosomes, and follicle stem cells in androgenetic alopecia: in vitro and in vivo analysis through a multicentric, observational, evaluator-blinded study.Aesthetic Plast Surg2025;49:43-58

[106] Gentile P,Bielli A.Platelet-rich plasma and micrografts enriched with autologous human follicle mesenchymal stem cells improve hair re-growth in androgenetic alopecia. biomolecular pathway analysis and clinical evaluation.Biomedicines2019;7:27 PMCID:PMC6631937

[107] Lam SM.Hair transplant and local anesthetics.Clin Plast Surg2013;40:615-25

[108] Patwardhan N, Mysore V; IADVL Dermatosurgery Task Force. Hair transplantation: standard guidelines of care. Indian J Dermatol Venereol Leprol. 2008;74:S46-53.

[109] Avram MR.Robotic hair transplantation.Facial Plast Surg Clin North Am2020;28:189-96

[110] Gentile P,Bielli A,Cervelli V.Stem cells from human hair follicles: first mechanical isolation for immediate autologous clinical use in androgenetic alopecia and hair loss.Stem Cell Investig2017;4:58 PMCID:PMC5504091

[111] Lee J,Gao H.Hair-bearing human skin generated entirely from pluripotent stem cells.Nature2020;582:399-404 PMCID:PMC7593871

[112] Kiso M,Itoh M,Nakagawa H.Synergistic effect of PDGF and FGF2 for cell proliferation and hair inductive activity in murine vibrissal dermal papilla in vitro.J Dermatol Sci2015;79:110-8

[113] Kang D,Qian C.3D bioprinting of a gelatin-alginate hydrogel for tissue-engineered hair follicle regeneration.Acta Biomater2023;165:19-30

[114] Li R,Zhang L.3D printing of microneedle arrays for hair regeneration in a controllable region.Mol Biomed2023;4:1 PMCID:PMC9816368

[115] Kageyama T,Myasnikova D.Spontaneous hair follicle germ (HFG) formation in vitro, enabling the large-scale production of HFGs for regenerative medicine.Biomaterials2018;154:291-300