Recent Advances in Microneedle Patches for Wound Healing

Document Type : Review article

Authors

1 Department of Nanobiotechnology and Biomimetics, Faculty of Life Science Engineering, College of Interdisciplinary Science and Technology, University of Tehran, Tehran, Iran

2 Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran

10.22038/mjms.2025.80281.4631

Abstract

Chronic wounds are typically covered with a layer of hardened skin and necrotic tissue, which significantly reduces the bioavailability of drug delivery due to the presence of various enzymes in the wound environment. Microneedle patches (MPs) can facilitate effective drug delivery by creating micron-sized channels within the skin, thereby enhancing the therapeutic effects of administered drugs or active substances. Given their advantages, including minimal invasiveness, painlessness, and ease of use, microneedle patches have been extensively studied in the field of biomedicine. This study systematically examines the wound healing process, encompassing haemostasis, inflammation, proliferation, and remodelling, along with its implications. It also explores the functionality, types (solid, coated, dissolving, hollow, and hydrogel), and benefits of microneedle patches (MPs). Furthermore, it discusses preparation methods (mold or mold-free), engineering design, and performance optimisation for the fabrication of medical MPs, as well as characterisation and diagnostic and therapeutic applications of MPs. Finally, the challenges and future perspectives regarding microneedle patches are addressed.

Keywords

Main Subjects


  1. Blacklow S, Li J, Freedman B, Zeidi M, Chen C, Mooney D. Bioinspired mechanically active adhesive dressings to accelerate wound closure. Science advances. 2019;5(7):eaaw3963.
  2. Farahani M, Shafiee A. Wound healing: From passive to smart dressings. Advanced Healthcare Materials. 2021;10(16):2100477.
  3. Lindholm C, Searle R. Wound management for the 21st century: combining effectiveness and efficiency. International wound journal. 2016;13:5-15.
  4. https://diabetesatlas.org/ 2025 [
  5. Raziyeva K, Kim Y, Zharkinbekov Z, Kassymbek K, Jimi S, Saparov A. Immunology of acute and chronic wound healing. Biomolecules. 2021;11(5):700.
  6. Fife CE, Eckert KA, Carter MJ. Publicly reported wound healing rates: the fantasy and the reality. Advances in wound care. 2018;7(3):77-94.
  7. Derakhshandeh H, Aghabaglou F, McCarthy A, Mostafavi A, Wiseman C, Bonick Z, et al. A wirelessly controlled smart bandage with 3D‐printed miniaturized needle arrays. Advanced functional materials. 2020;30(13):1905544.
  8. Barnum L, Samandari M, Schmidt TA, Tamayol A. Microneedle arrays for the treatment of chronic wounds. Expert opinion on drug delivery. 2020;17(12):1767-80.
  9. Demidova-Rice TN, Hamblin MR, Herman IM. Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 1: normal and chronic wounds: biology, causes, and approaches to care. Advances in skin & wound care. 2012;25(7):304.
  10. https://pureseoul.co.uk/products/soothing-q-microneedle-patches-12-pack [
  11. https://wrinklesschminkles.co.uk/products/self-dissolving-microneedle-patches-x-8 [
  12. https://www.amazon.co.uk/PATCH-PRO-self-dissolving-microneedle-anti-wrinkle/dp/B07JZ6S64M [
  13. https://www.strouse.com/blog/microneedle-patches [
  14. Hariharan A, Tran SD. Localized Drug Delivery Systems: An Update on Treatment Options for Head and Neck Squamous Cell Carcinomas. Pharmaceutics. 2023;15(7):1844.
  15. Samandari M, Aghabaglou F, Nuutila K, Derakhshandeh H, Zhang Y, Endo Y, et al. Miniaturized needle Array‐mediated drug delivery accelerates wound healing. Advanced Healthcare Materials. 2021;10(8):2001800.
  16. Sattar H, Bajwa IS, ul Amin R, Muhammad J, Mushtaq MF, Kazmi R, et al. Smart wound hydration monitoring using biosensors and fuzzy inference system. Wireless Communications and Mobile Computing. 2019;2019:1-15.
  17. Kruse CR, Nuutila K, Lee CC, Kiwanuka E, Singh M, Caterson EJ, et al. The external microenvironment of healing skin wounds. Wound Repair and Regeneration. 2015;23(4):456-64.
  18. Mariani F, Serafini M, Gualandi I, Arcangeli D, Decataldo F, Possanzini L, et al. Advanced wound dressing for real-time pH monitoring. ACS sensors. 2021;6(6):2366-77.
  19. Teymourian H, Tehrani F, Mahato K, Wang J. Lab under the skin: microneedle based wearable devices. Advanced healthcare materials. 2021;10(17):2002255.
  20. Hu F, Gao Q, Liu J, Chen W, Zheng C, Bai Q, et al. Smart microneedle patches for wound healing and management. Journal of Materials Chemistry B. 2023;11(13):2830-51.
  21. Chua AWC, Khoo YC, Tan BK, Tan KC, Foo CL, Chong SJ. Skin tissue engineering advances in severe burns: review and therapeutic applications. Burns & trauma. 2016;4:s41038-016-0027-y.
  22. Moeini A, Pedram P, Makvandi P, Malinconico M, d'Ayala GG. Wound healing and antimicrobial effect of active secondary metabolites in chitosan-based wound dressings: A review. Carbohydrate polymers. 2020;233:115839.
  23. Liang Y, He J, Guo B. Functional hydrogels as wound dressing to enhance wound healing. ACS nano. 2021;15(8):12687-722.
  24. Chen Z, Ren L, Li J, Yao L, Chen Y, Liu B, Jiang L. Rapid fabrication of microneedles using magnetorheological drawing lithography. Acta Biomaterialia. 2018;65:283-91.
  25. Zhang X, Chen G, Cai L, Wang Y, Sun L, Zhao Y. Bioinspired pagoda-like microneedle patches with strong fixation and hemostasis capabilities. Chemical Engineering Journal. 2021;414:128905.
  26. Ling J, Song Z, Wang J, Chen K, Li J, Xu S, et al. Effect of honeybee stinger and its microstructured barbs on insertion and pull force. Journal of the mechanical behavior of biomedical materials. 2017;68:173-9.
  27. Das R, Yadav RN, Sihota P, Uniyal P, Kumar N, Bhushan B. Biomechanical evaluation of wasp and honeybee stingers. Scientific reports. 2018;8(1):1-13.
  28. Guo M, Wang Y, Gao B, He B. Shark tooth-inspired microneedle dressing for intelligent wound management. ACS nano. 2021;15(9):15316-27.
  29. Matoori S, Veves A, Mooney DJ. Advanced bandages for diabetic wound healing. Science translational medicine. 2021;13(585):eabe4839.
  30. Jeon EY, Lee J, Kim BJ, Joo KI, Kim KH, Lim G, Cha HJ. Bio-inspired swellable hydrogel-forming double-layered adhesive microneedle protein patch for regenerative internal/external surgical closure. Biomaterials. 2019;222:119439.
  31. Wang Y, Lu H, Guo M, Chu J, Gao B, He B. Personalized and programmable microneedle dressing for promoting wound healing. Advanced Healthcare Materials. 2022;11(2):2101659.
  32. Gurera D, Bhushan B, Kumar N. Lessons from mosquitoes’ painless piercing. Journal of the mechanical behavior of biomedical materials. 2018;84:178-87.
  33. Zhang X, Chen G, Sun L, Ye F, Shen X, Zhao Y. Claw-inspired microneedle patches with liquid metal encapsulation for accelerating incisional wound healing. Chemical Engineering Journal. 2021;406:126741.
  34. Zhang X, Fu X, Chen G, Wang Y, Zhao Y. Versatile ice microneedles for transdermal delivery of diverse actives. Advanced Science. 2021;8(17):2101210.
  35. Madni A, Kousar R, Naeem N, Wahid F. Recent advancements in applications of chitosan-based biomaterials for skin tissue engineering. Journal of Bioresources and Bioproducts. 2021;6(1):11-25.
  36. Chogan F, Mirmajidi T, Rezayan AH, Sharifi AM, Ghahary A, Nourmohammadi J, et al. Design, fabrication, and optimization of a dual function three-layer scaffold for controlled release of metformin hydrochloride to alleviate fibrosis and accelerate wound healing. Acta biomaterialia. 2020;113:144-63.
  37. Oroojalian F, Jahanafrooz Z, Chogan F, Rezayan AH, Malekzade E, Rezaei SJT, et al. Synthesis and evaluation of injectable thermosensitive penta‐block copolymer hydrogel (PNIPAAm‐PCL‐PEG‐PCL‐PNIPAAm) and star‐shaped poly (CL─ CO─ LA)‐b‐PEG for wound healing applications. Journal of cellular biochemistry. 2019;120(10):17194-207.
  38. Abbasizadeh N, Rezayan AH, Nourmohammadi J, Kazemzadeh-Narbat M. HHC-36 antimicrobial peptide loading on silk fibroin (SF)/hydroxyapatite (HA) nanofibrous-coated titanium for the enhancement of osteoblast and bactericidal functions. International Journal of Polymeric Materials and Polymeric Biomaterials. 2019.
  39. Moaddab M, Nourmohammadi J, Rezayan AH. Bioactive composite scaffolds of carboxymethyl chitosan-silk fibroin containing chitosan nanoparticles for sustained release of ascorbic acid. European polymer journal. 2018;103:40-50.
  40. Firoozi N, Rezayan AH, Tabatabaei Rezaei SJ, Mir-Derikvand M, Nabid MR, Nourmohammadi J, Mohammadnejad Arough J. Synthesis of poly (ε-caprolactone)-based polyurethane semi-interpenetrating polymer networks as scaffolds for skin tissue regeneration. International Journal of Polymeric Materials and Polymeric Biomaterials. 2017;66(16):805-11.
  41. Najafi Tireh Shabankareh A, Ghanbari H, Samadi Pakchin P. Development of a New Electroconductive Nanofibrous Cardiac Patch Based on Polyurethane-Reduced Graphene Oxide Nanocomposite Scaffolds. Hossein and Samadi Pakchin, Parvin, Development of a New Electroconductive Nanofibrous Cardiac Patch Based on Polyurethane-Reduced Graphene Oxide Nanocomposite Scaffolds.
  42. Asghari F, Faradonbeh DR, Malekshahi ZV, Nekounam H, Ghaemi B, Yousefpoor Y, et al. Hybrid PCL/chitosan-PEO nanofibrous scaffolds incorporated with A. euchroma extract for skin tissue engineering application. Carbohydrate polymers. 2022;278:118926.
  43. Doostan M, Doostan M, Maleki H, Faridi Majidi R, Bagheri F, Ghanbari H. Co-electrospun poly (vinyl alcohol)/poly (ɛ-caprolactone) nanofiber scaffolds containing coffee and Calendula officinalis extracts for wound healing applications. Journal of Bioactive and Compatible Polymers. 2022;37(6):437-52.
  44. Sa’adon S, Ansari MNM, Razak SIA, Yusof AHM, Faudzi AAM, Sagadevan S, et al. Electrospun Nanofiber and Cryogel of Polyvinyl Alcohol Transdermal Patch Containing Diclofenac Sodium: Preparation, Characterization and In Vitro Release Studies. Pharmaceutics. 2021;13(11):1900.
  45. Sarwar MN, Ullah A, Haider M, Hussain N, Ullah S, Hashmi M, et al. Evaluating antibacterial efficacy and biocompatibility of PAN nanofibers loaded with diclofenac sodium salt. Polymers. 2021;13(4):510.
  46. Shokraei S, Mirzaei E, Shokraei N, Derakhshan MA, Ghanbari H, Faridi‐Majidi R. Fabrication and characterization of chitosan/kefiran electrospun nanofibers for tissue engineering applications. Journal of Applied Polymer Science. 2021;138(24):50547.
  47. Ziaei Amiri F, Pashandi Z, Lotfibakhshaiesh N, Mirzaei-Parsa MJ, Ghanbari H, Faridi-Majidi R. Cell attachment effects of collagen nanoparticles on crosslinked electrospun nanofibers. The International Journal of Artificial Organs. 2021;44(3):199-207.
  48. Hussein MAM, Su S, Ulag S, Woźniak A, Grinholc M, Erdemir G, et al. Development and in vitro evaluation of biocompatible pla-based trilayer nanofibrous membranes for the delivery of nanoceria: a novel approach for diabetic wound healing. Polymers. 2021;13(21):3630.
  49. Razzaq A, Khan ZU, Saeed A, Shah KA, Khan NU, Menaa B, et al. Development of cephradine-loaded gelatin/polyvinyl alcohol electrospun nanofibers for effective diabetic wound healing: in-vitro and in-vivo assessments. Pharmaceutics. 2021;13(3):349.
  50. Ahsan A, Tian W-X, Farooq MA, Khan DH. An overview of hydrogels and their role in transdermal drug delivery. International Journal of Polymeric Materials and Polymeric Biomaterials. 2021;70(8):574-84.
  51. Shafei S, Khanmohammadi M, Heidari R, Ghanbari H, Taghdiri Nooshabadi V, Farzamfar S, et al. Exosome loaded alginate hydrogel promotes tissue regeneration in full‐thickness skin wounds: An in vivo study. Journal of Biomedical Materials Research Part A. 2020;108(3):545-56.
  52. Rahmani M, Khani M-M, Rabbani S, Mashaghi A, Noorizadeh F, Faridi-Majidi R, Ghanbari H. Development of poly (mannitol sebacate)/poly (lactic acid) nanofibrous scaffolds with potential applications in tissue engineering. Materials Science and Engineering: C. 2020;110:110626.
  53. Eskandarinia A, Kefayat A, Agheb M, Rafienia M, Baghbadorani MA, Navid S, et al. A novel bilayer wound dressing composed of a dense polyurethane/propolis membrane and a biodegradable polycaprolactone/gelatin nanofibrous scaffold. Scientific reports. 2020;10(1):1-15.
  54. Brako F, Luo C, Matharu RK, Ciric L, Harker A, Edirisinghe M, Craig DQ. A Portable Device for the Generation of Drug-Loaded Three-Compartmental Fibers Containing Metronidazole and Iodine for Topical Application. Pharmaceutics. 2020;12(4):373.
  55. Jafari A, Amirsadeghi A, Hassanajili S, Azarpira N. Bioactive antibacterial bilayer PCL/gelatin nanofibrous scaffold promotes full-thickness wound healing. International journal of pharmaceutics. 2020;583:119413.
  56. Augustine R, Hasan A, Patan NK, Augustine A, Dalvi YB, Varghese R, et al. Titanium nanorods loaded PCL meshes with enhanced blood vessel formation and cell migration for wound dressing applications. Macromolecular bioscience. 2019;19(7):1900058.
  57. Mirzaei-Parsa MJ, Ghanbari H, Alipoor B, Tavakoli A, Najafabadi MRH, Faridi-Majidi R. Nanofiber-acellular dermal matrix as a bilayer scaffold containing mesenchymal stem cell for healing of full-thickness skin wounds. Cell and tissue research. 2019;375:709-21.
  58. Rezk AI, Lee JY, Son BC, Park CH, Kim CS. Bi-layered nanofibers membrane loaded with titanium oxide and tetracycline as controlled drug delivery system for wound dressing applications. Polymers. 2019;11(10):1602.
  59. Niranjan R, Kaushik M, Selvi RT, Prakash J, Venkataprasanna K, Prema D, et al. PVA/SA/TiO2-CUR patch for enhanced wound healing application: In vitro and in vivo analysis. International journal of biological macromolecules. 2019;138:704-17.
  60. Asadpour S, Yeganeh H, Khademi F, Ghanbari H, Ai J. Resveratrol-loaded polyurethane nanofibrous scaffold: viability of endothelial and smooth muscle cells. Biomedical Materials. 2019;15(1):015001.
  61. Prasanna A, Niranjan R, Kaushik M, Devasena T, Kumar J, Chelliah R, et al. Metal oxide curcumin incorporated polymer patches for wound healing. Applied Surface Science. 2018;449:603-9.
  62. Asadpour S, Yeganeh H, Ai J, Kargozar S, Rashtbar M, Seifalian A, Ghanbari H. Polyurethane-polycaprolactone blend patches: scaffold characterization and cardiomyoblast adhesion, proliferation, and function. ACS Biomaterials Science & Engineering. 2018;4(12):4299-310.
  63. Mirzaei-Parsa MJ, Ghanbari H, Bahrami N, Hadadi-Abianeh S, Faridi-Majidi R. The effects of cross-linked/uncross-linked electrospun fibrinogen/polycaprolactone nanofibers on the proliferation of normal human epidermal keratinocytes. Journal of Polymer Engineering. 2018;38(10):945-53.
  64. Zhang Y, Liu C, Wang J, Ren S, Song Y, Quan P, Fang L. Ionic liquids in transdermal drug delivery system: Current applications and future perspectives. Chinese Chemical Letters. 2023;34(3):107631.
  65. Yang L, Yang Y, Chen H, Mei L, Zeng X. Polymeric microneedle‐mediated sustained release systems: Design strategies and promising applications for drug delivery. Asian Journal of Pharmaceutical Sciences. 2022;17(1):70-86.
  66. Singh P, Carrier A, Chen Y, Lin S, Wang J, Cui S, Zhang X. Polymeric microneedles for controlled transdermal drug delivery. Journal of controlled release. 2019;315:97-113.
  67. Dabholkar N, Gorantla S, Waghule T, Rapalli VK, Kothuru A, Goel S, Singhvi G. Biodegradable microneedles fabricated with carbohydrates and proteins: Revolutionary approach for transdermal drug delivery. International Journal of Biological Macromolecules. 2021;170:602-21.
  68. Moniz T, Lima SAC, Reis S. Marine polymeric microneedles for transdermal drug delivery. Carbohydrate Polymers. 2021;266:118098.
  69. Rabiei M, Kashanian S, Samavati SS, Jamasb S, McInnes SJ. Nanomaterial and advanced technologies in transdermal drug delivery. Journal of drug targeting. 2020;28(4):356-67.
  70. Ebrahiminejad V, Prewett PD, Davies GJ, Faraji Rad Z. Microneedle arrays for drug delivery and diagnostics: toward an optimized design, reliable insertion, and penetration. Advanced Materials Interfaces. 2022;9(6):2101856.
  71. Chevala NT, Jitta SR, Marques SM, Vaz VM, Kumar L. Polymeric microneedles for transdermal delivery of nanoparticles: Frontiers of formulation, sterility and stability aspects. Journal of Drug Delivery Science and Technology. 2021;65:102711.
  72. Chen Y-C, Chen S-J, Cheng H-F, Yeh M-K. Development of Yersinia pestis F1 antigen-loaded liposome vaccine against plague using microneedles as a delivery system. Journal of Drug Delivery Science and Technology. 2020;55:101443.
  73. Waghule T, Singhvi G, Dubey SK, Pandey MM, Gupta G, Singh M, Dua K. Microneedles: A smart approach and increasing potential for transdermal drug delivery system. Biomedicine & pharmacotherapy. 2019;109:1249-58.
  74. Xu J, Xu D, Xuan X, He H. Advances of microneedles in biomedical applications. Molecules. 2021;26(19):5912.
  75. Zhang X, Wang Y, Chi J, Zhao Y. Smart microneedles for therapy and diagnosis. Research. 2020.
  76. Azmana M, Mahmood S, Hilles AR, Mandal UK, Al-Japairai KAS, Raman S. Transdermal drug delivery system through polymeric microneedle: A recent update. Journal of Drug Delivery Science and Technology. 2020;60:101877.
  77. Römgens A, Bader D, Bouwstra J, Baaijens F, Oomens C. Monitoring the penetration process of single microneedles with varying tip diameters. journal of the mechanical behavior of biomedical materials. 2014;40:397-405.
  78. Saha I, Rai VK. Hyaluronic acid based microneedle array: Recent applications in drug delivery and cosmetology. Carbohydrate Polymers. 2021;267:118168.
  79. Yao S, Wang Y, Chi J, Yu Y, Zhao Y, Luo Y, Wang Y. Porous MOF microneedle array patch with photothermal responsive nitric oxide delivery for wound healing. Advanced Science. 2022;9(3):2103449.
  80. Chi J, Zhang X, Chen C, Shao C, Zhao Y, Wang Y. Antibacterial and angiogenic chitosan microneedle array patch for promoting wound healing. Bioactive materials. 2020;5(2):253-9.
  81. Hu X, Zhang H, Wang Z, Shiu CYA, Gu Z. Microneedle array patches integrated with nanoparticles for therapy and diagnosis. Small Structures. 2021;2(4):2000097.
  82. Chen Q, Zhao Y, Liu Y. Current development in wearable glucose meters. Chinese Chemical Letters. 2021;32(12):3705-17.
  83. He R, Liu H, Fang T, Niu Y, Zhang H, Han F, et al. A Colorimetric Dermal Tattoo Biosensor Fabricated by Microneedle Patch for Multiplexed Detection of Health‐Related Biomarkers. Advanced Science. 2021;8(24):2103030.
  84. Zheng Y, Omar R, Zhang R, Tang N, Khatib M, Xu Q, et al. A wearable microneedle‐based extended gate transistor for real‐time detection of sodium in interstitial fluids. Advanced Materials. 2022;34(10):2108607.
  85. Pan P, Liu Q, Wang L, Wang C, Hu L, Jiang Y, et al. Recent Advances in Multifunctional Microneedle Patches for Wound Healing and Health Monitoring. Advanced NanoBiomed Research. 2023;3(2):2200126.
  86. Yao S, Luo Y, Wang Y. Engineered microneedles arrays for wound healing. Engineered Regeneration. 2022;3(3):232-40.
  87. Shi H, Zhou J, Wang Y, Zhu Y, Lin D, Lei L, et al. A rapid corneal healing microneedle for efficient ocular drug delivery. Small. 2022;18(4):2104657.
  88. Wang QL, Zhu DD, Chen Y, Guo XD. A fabrication method of microneedle molds with controlled microstructures. Materials Science and Engineering: C. 2016;65:135-42.
  89. Li S, Wang X, Yan Z, Wang T, Chen Z, Song H, Zheng Y. Microneedle Patches with Antimicrobial and Immunomodulating Properties for Infected Wound Healing. Advanced Science. 2023:2300576.
  90. Fu X, Zhang X, Huang D, Mao L, Qiu Y, Zhao Y. Bioinspired adhesive microneedle patch with gemcitabine encapsulation for pancreatic cancer treatment. Chemical Engineering Journal. 2022;431:133362.
  91. Wang Y, Chen G, Zhang H, Zhao C, Sun L, Zhao Y. Emerging functional biomaterials as medical patches. Acs Nano. 2021;15(4):5977-6007.
  92. Lei Q, He D, Ding L, Kong F, He P, Huang J, et al. Microneedle patches integrated with biomineralized melanin nanoparticles for simultaneous skin tumor photothermal therapy and wound healing. Advanced Functional Materials. 2022;32(22):2113269.
  93. Sun L, Fan L, Bian F, Chen G, Wang Y, Zhao Y. MXene-integrated microneedle patches with innate molecule encapsulation for wound healing. Research. 2021.
  94. Aldawood FK, Andar A, Desai S. A comprehensive review of microneedles: Types, materials, processes, characterizations and applications. Polymers. 2021;13(16):2815.
  95. Yin M, Wu J, Deng M, Wang P, Ji G, Wang M, et al. Multifunctional magnesium organic framework-based microneedle patch for accelerating diabetic wound healing. Acs Nano. 2021;15(11):17842-53.
  96. Cheng Y, Gong X, Yang J, Zheng G, Zheng Y, Li Y, et al. A touch-actuated glucose sensor fully integrated with microneedle array and reverse iontophoresis for diabetes monitoring. Biosensors and Bioelectronics. 2022;203:114026.
  97. Tehrani F, Teymourian H, Wuerstle B, Kavner J, Patel R, Furmidge A, et al. An integrated wearable microneedle array for the continuous monitoring of multiple biomarkers in interstitial fluid. Nature Biomedical Engineering. 2022;6(11):1214-24.
  98. Alshammari MK, Ghazwani JA, Alsharari FO, Alotaibi SS, Alotaibi RM, Alsayahani AA, et al. An update on microneedle in insulin delivery: Quality attributes, clinical status and challenges for clinical translation. Journal of Drug Delivery Science and Technology. 2022:103668.
  99. Xiu X, Gao G, Liu Y, Ma F. Drug delivery with dissolving microneedles: Skin puncture, its influencing factors and improvement strategies. Journal of Drug Delivery Science and Technology. 2022;76:103653.
  100. Chen X, Wang L, Yu H, Li C, Feng J, Haq F, et al. Preparation, properties and challenges of the microneedles-based insulin delivery system. Journal of Controlled Release. 2018;288:173-88.