Researchers have developed an advanced microneedle patch addressing chronic wound management by integrating drug delivery, therapeutic stimulation, and real-time monitoring. The innovation employs a laser defocusing strategy using CO2 laser technology, where negative defocusing positions the focal point below the material surface to achieve precise microneedle fabrication with tips as small as 2.2 micrometers. The resulting self-powered microneedle patch delivers electrical stimulation-triggered drug release, achieving approximately 80% cumulative drug delivery. Integrated colorimetric sensors enable continuous monitoring of wound temperature and pH levels. In vivo studies demonstrated significantly accelerated wound healing compared to conventional approaches. This multifunctional platform addresses critical limitations of existing microneedle techniques by simultaneously achieving high-precision fabrication, stimulation-responsive release, and physiological monitoring. The development represents a significant advance toward personalized therapeutic applications in chronic wound management, offering clinicians an integrated solution that combines diagnostic and treatment capabilities.

Researchers have developed bio-inspired microneedles for transdermal drug delivery by emulating the structural geometry of honeybee stingers. Traditional microneedle designs suffer from poor tissue retention, inconsistent skin penetration, and mechanical failure. By mimicking the backward-facing barbs and graduated size profile found in bee stingers, scientists created an optimized microneedle patch using liquid crystal display 3D printing technology. The team systematically optimized three parameters: base diameter, barb angle, and barb quantity. The optimal design features a 1.75 millimeter base diameter, 45-degree barb angle, and seven barbs per side. Testing demonstrated a 3.5-fold improvement in tensile retention force compared to conventional designs, requiring 0.45 newtons to dislodge a single needle, while maintaining low insertion force at 0.18 newtons, comparable to acupuncture needles. This biomimetic approach successfully balances high adhesion with minimal insertion pain, establishing substantial potential for long-term controlled transdermal pharmaceutical delivery applications.

Microarray patches represent a transformative approach to needle-free drug delivery, as detailed in a comprehensive critical narrative review published in the Journal of Pharmacy and Pharmaceutical Sciences by an international multidisciplinary research team. These micron-scale projection arrays, typically ranging from 50 to 900 micrometers in height, breach the skin's outer layer to deliver therapeutic payloads directly into the immunologically rich viable epidermis and dermis, bypassing limitations of conventional hypodermic needles that require trained personnel, demand cold-chain infrastructure, generate biohazardous waste, and cause injection-associated pain. The biological rationale centers on targeting antigen-presenting cells abundantly present in skin layers—Langerhans cells and dermal dendritic cells contain one to two orders of magnitude more such cells per unit volume than subcutaneous muscle tissue. This concentrated cellular activation enables dose sparing, allowing protective immune responses using only fractional standard antigen quantities required by intramuscular injections. Beyond prophylactic vaccines, microarray patches offer applications in transdermal diagnostics, chemotherapeutics, and biotherapeutics including monoclonal antibodies. While five distinct operational classifications exist, the review emphasizes that rigorous chemistry, manufacturing, and control hurdles remain before commercial scale production becomes viable, positioning these devices as a critical innovation for global vaccination and therapeutic delivery programs.

Microneedle-based vaccine patches offer a promising solution to address critical limitations of messenger RNA vaccines, according to a comprehensive review published in AAPS Open by researchers including Lauren Levy, Robert Langer, and Ana Jaklenec. While mRNA vaccines proved effective during the COVID-19 pandemic, their widespread distribution remains hindered by temperature sensitivity, complex cold-chain requirements, and multiple-dose administration challenges. Microneedle patches deliver vaccine formulations directly into the skin, triggering immune responses through Langerhans cells and dermal dendritic cells while reducing antigen quantities and eliminating conventional needles. The review specifically highlights dissolving microneedle patches as particularly promising, utilizing biodegradable, water-soluble polymers including polyvinylpyrrolidone, polyvinyl alcohol, carboxymethylcellulose, and hyaluronic acid to encapsulate lipid nanoparticle-based mRNA. Research from the Jaklenec laboratory demonstrates that optimized drying methods and excipient combinations can preserve mRNA biological activity under ambient and elevated temperatures. Successful development requires carefully balancing needle strength, dissolution rates, moisture content, polymer composition, and mRNA stability through quality-by-design manufacturing approaches. This technology represents significant potential for improving vaccine stability, accessibility, and ease of administration for next-generation immunotherapies.

Researchers Sudhanshu Kalantri, Anuj N. Nahata, and Nandan Godani published a comprehensive analytical review in Discover Pharmaceutical Sciences examining the integration of microneedle platforms with biosensing technologies for minimally invasive transdermal drug delivery and continuous biomarker monitoring. The review synthesizes advances in device architectures, microfabrication techniques, transducing mechanisms, and self-powered energy sources, demonstrating applications across chronic metabolic, oncological, neurological, and renal conditions. Microneedles feature microscopic geometries with pointed tips that breach the skin barrier to create temporary microchannels. Advanced imaging techniques including fluorescence lifetime imaging microscopy and cryo-scanning electron microscopy reveal that approximately 25 percent of these microchannels reseal within 20 minutes, with complete barrier closure occurring within six hours. This predictable resealing profile enables effective transdermal fluid sampling and drug delivery while maintaining skin integrity. The review categorizes five distinct structural microneedle types, including solid variants fabricated from stainless steel, titanium, silicon, or gold-coated substrates that enhance bioavailability, and hollow microneedles featuring internal conduits for administering precise drug volumes or extracting interstitial fluids through passive diffusion.

Transdermal drug delivery has long been limited by the skin's complex barrier structure, particularly the stratum corneum, which prevents penetration of most therapeutic molecules. Microneedle patch technology represents a breakthrough approach to overcome these limitations by creating microchannels through the skin's outer layer in a minimally invasive, painless manner. This advancement enables enhanced permeability for a broad spectrum of pharmacologically active molecules that would otherwise be unable to penetrate the skin barrier. Unlike traditional transdermal delivery restricted to small, lipophilic compounds, microneedle patches bypass the stratum corneum's selective barrier function while preserving the skin's protective role across its three layers: the epidermis, dermis, and hypodermis. By circumventing first-pass metabolism associated with oral routes and the invasiveness of injectable delivery, microneedle technology offers a more convenient and effective therapeutic option. This innovation is particularly significant for delivering larger molecules and hydrophilic drugs that previously could not be administered transdermally, potentially expanding treatment possibilities across multiple therapeutic areas and improving patient compliance through painless, self-administered dosing.

# Professional Summary Researchers have developed dissolving microneedles as an innovative intradermal drug delivery system for treating psoriasis. This advanced technology utilizes microneedle arrays that penetrate the skin to deliver therapeutic agents directly into the dermis, where they dissolve and release medication at the target site. The microneedle approach addresses significant limitations of conventional psoriasis treatments, including poor skin penetration and systemic side effects associated with oral or injectable medications. By enabling localized, sustained drug delivery, the dissolving microneedle platform potentially improves therapeutic efficacy while minimizing systemic exposure and associated adverse effects. This intradermal delivery mechanism represents a promising alternative to existing treatment modalities, offering patients enhanced tolerability and treatment outcomes. The technology demonstrates the potential to transform psoriasis management by providing a more precise, patient-friendly administration route that could improve compliance and clinical outcomes for this chronic inflammatory skin condition affecting millions globally.

Researchers have developed an innovative approach to treating diabetic wounds by engineering delivery systems for Chinese herbal medicine-derived therapeutics. This study, published in Frontiers in Bioengineering and Biotechnology, focuses on modulating the NF-κB cascade—a critical inflammatory pathway implicated in impaired wound healing. The research leverages advanced biomaterial technologies to enable targeted, localized exposure of herbal compounds to affected tissue, enhancing their therapeutic efficacy while minimizing systemic side effects. By concentrating bioactive molecules at wound sites through engineered delivery mechanisms, the approach addresses a significant clinical challenge: diabetic wounds heal poorly due to prolonged inflammation and dysregulated tissue repair processes. This integration of traditional herbal medicine with modern bioengineering represents a promising avenue for improving diabetic wound management, potentially offering patients more effective and naturally-derived treatment options compared to conventional therapies while reducing complications associated with chronic non-healing wounds.

A comprehensive review in Materials Today Bio examines the development and applications of microneedle-based platforms for gene therapy delivery. Gene therapy aims to correct abnormal gene expression by introducing exogenous genetic material or editing specific genes, with expanding clinical applications across monogenic disorders, oncology, metabolic diseases, and neurodegenerative conditions. However, delivering therapeutic nucleic acids—including plasmid DNA, messenger RNA, small interfering RNA, and CRISPR-Cas complexes—remains a critical challenge due to their large molecular weights, hydrophilicity, negative charges, and susceptibility to nuclease degradation. Conventional delivery methods such as systemic intravenous injections suffer from nuclease breakdown and off-target distribution, while standard hypodermic injections show poor retention. Microneedle arrays, consisting of micro-projections spanning tens to thousands of micrometers, overcome these limitations by penetrating tissue barriers minimally invasively and creating temporary microchannels that deliver therapeutic payloads directly into the epidermis and dermis. This approach significantly enhances local retention and bioavailability while reducing systemic circulation and adverse effects. Fabrication techniques, including microelectromechanical systems etching and micromolding, determine the physical characteristics and cargo stability of microneedle arrays, making this technology increasingly relevant for advancing gene therapy clinical translation.

This laboratory research program focuses on advancing skin-interfaced bioelectronic technologies for non-invasive physiological monitoring and neural interfaces. The research encompasses five interconnected areas: designing ultrathin, conformal skin electrodes that minimize impedance instability and motion artifacts for reliable ECG monitoring and skin hydration sensing; developing fully biomaterial-based biosemiconductor devices that enable adaptive charge transport with multifunctional capabilities including UV photodetection and synaptic emulation; creating nanofabrication methods for biomaterials through silk-protein-based electron beam lithography, deep ultraviolet photolithography, and two-photon lithography for biocompatible nanodevices; engineering nanoscale photonic structures including protein-based color filters, photonic crystals, and plasmonic biosensors for precise light modulation at nanoscale dimensions; and developing silk-based microneedle electrodes that penetrate the stratum corneum to directly interface with underlying tissue. These integrated technologies establish biomaterial-based platforms for adaptive sensing, optoelectronics, and neuromorphic bioelectronics, addressing fundamental challenges in reliable bioelectrical signal acquisition and advancing human-machine interfaces through biocompatible innovations.

Researchers have developed an innovative therapeutic approach for psoriasis using ROS-responsive nanoparticle-loaded dissolving microneedles that deliver Piezo1 siRNA directly to affected skin. Published in the Journal of Nanobiotechnology in October 2026, this study leverages mechanotransduction mechanisms underlying psoriatic pathology. The dissolving microneedles serve as a minimally invasive delivery vehicle, dissolving upon skin contact to release nanoparticles engineered to respond to reactive oxygen species—molecules elevated in psoriatic lesions. By silencing Piezo1, a mechanosensitive ion channel implicated in inflammatory responses, the treatment targets the molecular basis of disease progression rather than merely addressing symptoms. This approach represents a significant advancement in localized gene therapy, offering potential benefits including reduced systemic side effects, improved patient compliance through painless administration, and enhanced therapeutic efficacy. The technology demonstrates how combining materials science, molecular biology, and transdermal delivery innovation can create novel treatment modalities for chronic inflammatory skin conditions, positioning this methodology as a promising avenue for future psoriasis management and potentially applicable to other mechanotransduction-driven diseases.

Needle-free vaccination methods represent a promising solution to improve immunization compliance and address public health challenges associated with traditional needle-and-syringe administration. While vaccines remain among the most cost-effective disease prevention strategies, low vaccination rates persist due to needle anxiety, the need for multiple doses, and concerns about sharps disposal and hazardous waste management. This article examines emerging needle-free technologies being developed by multiple companies to revolutionize vaccine delivery through transdermal and oral routes. Oral delivery faces significant obstacles, including degradation by stomach acid and proteases, requiring innovative solutions such as lipid encapsulation of protein antigens or development of live bacterial vaccine carriers that are inexpensive to manufacture, thermostable, easily administered, and inherently immunogenic. Transdermal approaches utilize needle-free devices delivering solid or liquid vaccine formulations, leveraging the skin's immune system, particularly Langerhans cells in the epidermis that serve as specialized antigen-presenting cells. These alternative delivery mechanisms offer convenience, eliminate sharps-related hazards, and may significantly enhance vaccine accessibility and public health outcomes globally.

Researchers have developed dissolving microneedle patches that deliver flu vaccines with efficacy matching that of traditional intramuscular injections. The patches, composed of dissolvable materials, contain flu vaccine antigens that penetrate the skin and dissolve upon contact, eliminating the need for needles and syringes. This innovative approach addresses significant challenges in vaccine administration, including needle anxiety, medical waste generation, and the need for trained personnel. The study demonstrated that immunogenicity levels achieved through microneedle patch delivery were comparable to standard flu shots, as measured by antibody responses in trial participants. This advancement holds substantial promise for improving vaccine accessibility and patient compliance, particularly in resource-limited settings where refrigeration and trained healthcare workers are scarce. The microneedle patch technology could streamline mass vaccination campaigns and reduce healthcare infrastructure burdens while maintaining clinical effectiveness. These findings suggest a paradigm shift in vaccine delivery methods, potentially transforming how influenza and other vaccines are administered globally.

# Professional Summary Researchers have developed innovative microneedles constructed from natural polysaccharides as a novel drug delivery platform. This technology addresses significant limitations of conventional injection methods by utilizing biocompatible, biodegradable polysaccharide-based materials to create micro-scale needle structures. The polysaccharide microneedles offer several advantages over synthetic alternatives, including enhanced biocompatibility, reduced immunogenicity, and sustainable sourcing from renewable materials. These microneedles can penetrate the skin barrier to deliver pharmaceutical agents directly into target tissues, enabling improved therapeutic efficacy while minimizing systemic exposure. The approach demonstrates particular promise for vaccine delivery, protein therapeutics, and pain management applications where transdermal administration is beneficial. By leveraging natural polymer chemistry, this technology represents a significant advancement in minimally invasive drug delivery systems, potentially transforming patient compliance and treatment outcomes across multiple therapeutic areas while maintaining environmental sustainability and safety profiles superior to conventional microneedle devices.

Researchers have developed mathematical models and mechanical analyses to optimize dissolving polymeric microneedles for reliable transdermal drug delivery. The study examines how microneedles withstand insertion forces without buckling or deforming, using Euler's column buckling formula and Smith's analytical model tailored for tapered geometries including conical and pyramidal structures. Critical findings reveal that sharp microneedle tips under 10 micrometers penetrate human stratum corneum requiring insertion forces between 0.02 and 0.20 newtons per needle. The Safety Factor—defined as the ratio of critical buckling load to skin insertion force—must exceed 2.0 to ensure successful penetration. High-aspect-ratio conical carboxymethyl cellulose needles showed inadequate critical buckling loads below 0.10 newtons, whereas obelisk-shaped hyaluronic acid and polyvinylpyrrolidone-K90 dissolving microneedles achieved Safety Factors of 7.5 to 15.0, guaranteeing 100 percent skin insertion success. This research matters because optimized microneedle design enhances transdermal delivery efficiency, reducing treatment failures and improving patient compliance for needle-based pharmaceutical applications.

Diabetic foot ulcers represent a significant global health challenge, characterized by hyperglycemic environments, persistent inflammation, oxidative stress, impaired angiogenesis, and recurrent infections that collectively impede healing and increase amputation risk. This review, published in the International Journal of General Medicine by researchers from Qingdao Municipal Hospital and affiliated institutions in China, examines polysaccharide-based biomaterials as promising solutions for wound repair. Natural polysaccharides offer biocompatibility, biodegradability, and low immunogenicity while providing multiple therapeutic functions including antibacterial, antioxidant, anti-inflammatory, pro-angiogenic, and immunomodulatory effects through macrophage polarization regulation. When incorporated into wound dressings, polysaccharide-derived formulations absorb exudate, maintain moist microenvironments, neutralize reactive oxygen species, suppress pathogens and biofilms, and promote angiogenesis and re-epithelialization to accelerate wound closure. Despite their therapeutic potential, clinical translation remains constrained by unclear structure-activity relationships, batch-to-batch inconsistencies, undefined molecular mechanisms, and scalable manufacturing limitations. This comprehensive review addresses these challenges by analyzing polysaccharide classifications and their applications in diabetic wound management, providing critical insights for advancing these biomaterials toward clinical implementation.

Alopecia, a multifactorial disorder causing progressive hair loss and follicular dysfunction, currently relies on conventional treatments with limited efficacy due to poor skin penetration and systemic side effects. Microneedle-based platforms represent an emerging minimally invasive solution capable of enhancing transdermal delivery directly to the follicular microenvironment. This review examines the design integration of microneedles with advanced encapsulation strategies, emphasizing their potential for immunomodulation and tissue regeneration in alopecia treatment. Recent technological advances incorporating nanoparticles, nanoliposomes, porous materials, microsphere-integrated microneedles, and light-guiding systems have significantly expanded conventional polymeric microneedles' capabilities beyond passive drug delivery. These platforms improve drug stability, regulate release kinetics, enhance follicular targeting, and actively modulate biological processes associated with alopecia pathogenesis. Reported therapeutic benefits include suppression of inflammatory signaling, regulation of immune-cell infiltration, stimulation of angiogenesis, reduction of oxidative stress, activation of follicular stem-cell populations, and promotion of the telogen-to-anagen transition. These encapsulation-integrated microneedle systems position themselves as a promising next-generation therapeutic platform offering sustained, controlled, and localized therapeutic exposure within the hair follicle niche.

Human skin, covering 1.5 to 2.0 m² and representing 15–16% of body weight, represents the most accessible yet challenging gateway for non-invasive drug delivery. Since scopolamine's market approval as a transdermal patch in 1979, the pharmacokinetic advantages have remained compelling: bypassing hepatic first-pass metabolism, maintaining steady plasma concentrations, and avoiding gastrointestinal degradation. Peptides and proteins, now exceeding one-tenth of the global pharmaceutical market, stand to benefit considerably, yet their physicochemical properties—ranging from 500 Da to beyond 150 kDa, hydrophilic, charged at physiological pH, and susceptible to proteolysis—fundamentally oppose the small, lipophilic, uncharged molecules that passive permeation favors. The stratum corneum's layered architecture, composed of anucleated corneocytes embedded in a specialized lipid matrix of ceramides, cholesterol, and fatty acids in orthorhombic crystalline packing, creates formidable barriers. The tortuous diffusion pathway extends effective distances to 450–500 μm despite tissue thickness of merely 10–20 μm, amplifying permeability challenges. Understanding these biological constraints is critical for developing next-generation transdermal therapeutics for macromolecular drugs.

Researchers have developed and optimized dissolvable polymeric microneedles (PMNs) as a novel transdermal drug delivery system to overcome limitations of oral medication, including first-pass metabolism. The study focused on hyaluronic acid-carboxymethylcellulose (HA-CMC) microneedles loaded with lawsone, a bioactive compound from Lawsonia inermis with documented antioxidant, anti-inflammatory, antimicrobial, and antitumor properties. Using the Box-Behnken design approach, researchers optimized concentrations of carboxymethylcellulose, hyaluronic acid, and polyethylene glycol 400 to enhance drug release. The formulation was fabricated via micromolding and characterized through scanning electron microscopy and various mechanical assessments. The optimized patches demonstrated cumulative drug release of 59.63% within 90 minutes following Higuchi release kinetics, uniform morphology, a failure force of 0.48 N, and full skin penetration of 375 micrometers with reversible transepidermal water loss changes. This biocompatible HA-CMC platform provides a promising foundation for painless, controlled transdermal delivery of lawsone for anti-inflammatory and antitumor applications, though further in vivo validation is required.

Hydrogel microneedles represent an emerging technology for transdermal drug delivery and interstitial fluid sampling with potential perioperative applications. This narrative review examines how material design influences delivered drug doses, measurement accuracy, and clinical feasibility in surgical settings. While human sampling studies have demonstrated feasibility for specific measurements, most therapeutic applications and integrated sensing functions remain largely at the preclinical stage. The review critically distinguishes findings from non-surgical contexts, emphasizing challenges unique to the operating room environment, including reliable insertion and adhesion on disinfected or compromised skin, correlations between interstitial and plasma measurements, and drug exposure when delivery is interrupted. The authors recommend focusing initial clinical studies on short-duration superficial procedures and wound-adjacent monitoring while maintaining standard perioperative care. They highlight that clinical translation requires comprehensive product validation encompassing sterilization protocols, batch consistency, shelf life stability, and safeguards against uncontrolled drug release. The review stresses that autonomous anesthetic administration, while a development goal, requires rigorous safety validation that cannot rely solely on separate demonstrations of sensing and drug release capabilities. Systematic reporting of failed applications and adverse events alongside patient outcomes is essential for advancing this technology toward clinical implementation.