Understanding Microneedles: From Basic Principles to Cutting-Edge Applications - A Micro-Scale Delivery Platform in Biomedical Engineering

In the context of rapid advancements in precision medicine and non-invasive diagnostics, microneedles (MNs) have garnered significant attention as a novel drug delivery system bridging the gap between traditional injections and transdermal patches. Their unique structural design and multifunctional integration capabilities demonstrate immense potential in fields such as controlled drug release, biosensing, and vaccine delivery. This article systematically reviews the research progress and development prospects of microneedle technology from four aspects: basic definition, application areas, common biomaterials and their properties, and mainstream fabrication processes.

01. What Are Microneedles? Structural Features and Working Principles

Microneedles refer to miniature needle-like array structures with a height of 50–2000 μm​ and a tip diameter of <100 μm. Typically arranged in high density on a substrate, they form a patch-like device. Their core mechanism involves mechanically penetrating the skin's stratum corneum​ to form temporary microchannels within the epidermis without touching pain nerve endings, thereby achieving effective transmembrane delivery of macromolecular drugs, nucleic acids, vaccines, and more.

Based on functional response mechanisms, microneedles can be categorized as follows:

(Note: The original text refers to Figure 1 here)

Figure 1. Classification of Microneedles [1]

This classification system reflects the high flexibility of microneedles in structure-function integrated design.

02. Application Progress of Microneedles in Biomedical Engineering and Related Fields

1. Transdermal Drug Delivery (TDD)

Traditional transdermal delivery is limited by the stratum corneum barrier, making it difficult to deliver macromolecules like proteins, peptides, and siRNA. Microneedles effectively overcome this limitation and have been successfully used for the transdermal delivery of insulin, monoclonal antibodies, and growth hormones, significantly enhancing bioavailability.

2. Vaccine Delivery Systems

Microneedle patches can stabilize antigens and adjuvants at room temperature, eliminating cold chain dependence. More importantly, they target the skin's rich antigen-presenting cells (e.g., Langerhans cells), eliciting a stronger immune response.

3. Biosensing & Point-of-Care Testing (POCT)

Integrated microneedle sensors can collect interstitial fluid (ISF) to monitor physiological indicators such as glucose, lactate, and inflammatory cytokines in real-time, replacing frequent blood draws.

4. Tumor Therapy and Local Intervention

Locally implanted drug-loaded microneedles can be used for targeted chemotherapy or immunomodulation of residual lesions after skin cancer or breast cancer surgery. Furthermore, stimulus-responsive microneedles combined with photothermal/magnetothermal materials are under active exploration.

5. Medical Aesthetics and Skin Repair

Encapsulating ingredients like hyaluronic acid and collagen in soluble microneedles promotes dermis regeneration, improving acne scars, pigmentation, and skin aging with high safety and efficacy.

(Note: The original text refers to Figure 2 here)

Figure 2. Applications of Microneedles [2]

03. Biomaterials for Microneedles and Their Performance Characteristics

Material selection directly determines the mechanical strength, degradation behavior, drug loading efficiency, and biocompatibility of microneedles. Currently, they are primarily divided into the following four categories:

⚠️ Note:​ All materials must meet the biological safety standards of ISO 10993​ to ensure no cytotoxicity, sensitization, or irritation. Additionally, composite material strategies (e.g., PLGA/HA blending) are becoming an important direction for enhancing overall performance.

04. Fabrication Methods: From Micro-Machining to Additive Manufacturing

Microneedle manufacturing integrates Micro-Electro-Mechanical Systems (MEMS), soft lithography, template replication, and advanced printing technologies. Typical processes are as follows:

Silicon Photolithography + Deep Reactive Ion Etching (DRIE):

Used to fabricate high-precision silicon molds.

Mature process, but high cost; suitable for prototype development.

PDMS Soft Template Replication (Molding):

Polymer solutions are cast into silicon molds, cured, and demolded.

Low cost and easy scalability make this a mainstream industrialization path.

3D Printing:

Includes inkjet printing, Stereolithography (SLA), and Digital Light Processing (DLP).

Supports personalized customization and complex geometric structures.

Resolution is gradually improving to the ±10 μm level.

Near-field Electrospinning:

Constructs nanofiber microneedle structures.

Suitable for high specific surface area drug delivery systems.

Current challenges lie in balancing resolution, production efficiency, and inter-batch consistency, especially for GMP-compliant production of clinical-grade products.

05. Outlook and Challenges

Although microneedle technology is developing rapidly, several key bottlenecks remain:

Stability and cost control for mass production.

Precise regulation of multi-dose/long-acting release systems.

In vivo degradation kinetics and pharmacokinetic models are not yet perfect.

Clinical translation paths are long, and regulatory approval systems are still being established.

However, with the deep integration of flexible electronics, smart materials, and AI-assisted design, the next generation of "Smart Microneedle Systems"​ is accelerating toward realization-closed-loop diagnostic and therapeutic platforms integrating sensing, response, and feedback are already taking shape.

Summary

Microneedles are more than just drug delivery tools; they are a cross-innovation platform connecting materials science, micro/nano manufacturing, biomedicine, and artificial intelligence. They represent a future medical paradigm characterized by "minimally invasive, high efficiency, and patient-friendly" treatment.