The rapid development of wearable biosensing calls for next-generation devices that allow continuous, real-time, and painless monitoring of health status along with responsive medical treatment. Microneedles have exhibited great potential for the direct access of dermal interstitial fluid (ISF) in a minimally invasive manner. Recent studies of microneedle-based devices have evolved from conventional off-line detection to multiplexed, wireless, and integrated sensing. In this review, the classification and fabrication techniques of microneedles are first introduced, and then the representative examples of microneedles for transdermal monitoring with different sensing modalities are summarized. State-of-the-art advances in therapeutic and closed-loop systems are presented to formulate guidelines for the development of next-generation microneedle-based healthcare platforms. The potential challenges and prospects are discussed to pave a new avenue toward pragmatic applications in the real world.

Wearable Clinic: From Microneedle-Based Sensors to Next-Generation Healthcare Platforms.

Microtechnology-based advanced drug delivery technique has significantly advanced, but experiences a few technological hurdles to achieve their full potential. With the fast advancement in diagnostic modes, drug delivery methodology is not restricted to only immunology or wound healing, but rather applicable to gene delivery, and cancer treatments which demand a controlled discharge of targeted drug transferring. Again, nanofluids are acknowledged in nano-biomedical technology. The heat-generating magnetic nanoparticles due to a high magnetic field would locally heat up tissue and thus detect hyperthermia. Microfluidic control released drug delivery technology offers a unique technology to implement nanofluidic drug delivery. With such an objective, this investigation explores the MWCNT-Fe3O4-water hybrid nanofluidic transport through a micro-wavy channel. Along the channel's perpendicular axis direction, a uniform magnetic field is operated. During the numeric exercise, three different micro-wavy channel textures are designed to facilitate the drug delivery application in MEMS-based medical devices. The channel's entry and exit sections are planar surfaces, while the middle section is engineered to have a wavy texture. The non-wavy sections are insulated, whereas the wavy walls are heated. The major flow equations after performing non-dimensionalization are resolved with the Galerkin-finite-element scheme. Both numerical and experimental assessments are performed with existing literature to establish the current simulation-based model's legitimacy. Several velocities, streamlines, and heat transference graphics are extracted from those three different wavy channels. The acting magnetic intensity decelerates the flow transit but enhances the heat transmission. Numeric simulation predicts 17.91% heat transference augmentation at the lower wavy surface for increasing amplitude-based micro wavy channel, while the decreasing amplitude micro wavy channel estimates 12.20% heat transference increment. The numeric scrutiny conveys that increasing or decreasing amplitude-based wavy texture facilitates the flow most and accelerates heat transference compared to simple uniform amplitude-based wavy texture surfaces. 

Magnetically Driven MWCNT-Fe3O4-water Hybrid Nanofluidic Transport through a Micro-Wavy Channel: A Novel MEMS Design for Drug Delivery Application

Hypoxia and infection are urgent clinical problems in chronic diabetic wounds. Herein, living Chlorella‐loaded poly(ionic liquid)‐based microneedles (PILMN‐Chl) are constructed for microacupuncture oxygen and antibacterial therapy against methicillin‐resistant Staphylococcus aureus (MRSA)‐infected chronic diabetic wounds. The PILMN‐Chl can stably and continuously produce oxygen for more than 30 h due to the photosynthesis of the loaded self‐supported Chlorella. By combining the barrier penetration capabilities of microneedles, the continuous and sufficient oxygen supply of Chlorella, and the sterilization activities of PIL, the PILMN‐Chl can accelerate chronic diabetic wounds in vivo by topical targeted sterilization and hypoxia relief in deep parts of wounds. Thus, the self‐oxygen produced microneedles modality may provide a promising and facile therapeutic strategy for treating chronic, hypoxic, and infected diabetic wounds.

Chlorella-Loaded Antibacterial Microneedles for Microacupuncture Oxygen Therapy of Diabetic Bacterial Infected Wounds.

The delivery of therapeutical molecules through the skin, particularly to its deeper layers, is impaired due to the stratum corneum layer, which acts as a barrier to foreign substances. Thus, for the past years, scientists have focused on the development of more efficient methods to deliver molecules to skin distinct layers. Microneedles, as a new class of biomedical devices, consist of an array of microscale needles. This particular biomedical device has been drawing attention due to its ability to breach the stratum corneum, forming micro-conduits to facilitate the passage of therapeutical molecules. The microneedle device has several advantages over conventional methods, such as better medication adherence, easiness, and painless self-administration. Moreover, it is possible to deliver the molecules swiftly or over time. Microneedles can vary in shape, size, and composition. The design process of a microneedle device must take into account several factors, like the location delivery, the material, and the manufacturing process. Microneedles have been used in a large number of fields from drug and vaccine application to cosmetics, therapy, diagnoses, tissue engineering, sample extraction, cancer research, and wound healing, among others.

Microneedles’ Device: Design, Fabrication, and Applications

Tissue injury is a common clinical problem, which may cause great burden on patients' life. It is important to develop functional scaffolds to promote tissue repair and regeneration. Due to their unique composition and structure, microneedles have attracted extensive attention in various tissues regeneration, including skin wound, corneal injury, myocardial infarction, endometrial injury, and spinal cord injury et al. Microneedles with micro-needle structure can effectively penetrate the barriers of necrotic tissue or biofilm, therefore improving the bioavailability of drugs. The use of microneedles to deliver bioactive molecules, mesenchymal stem cells, and growth factors in situ allows for targeted tissue and better spatial distribution. At the same time, microneedles can also provide mechanical support or directional traction for tissue, thus accelerating tissue repair. This review summarized the research progress of microneedles for in situ tissue regeneration over the past decade. At the same time, the shortcomings of existing researches, future research direction and clinical application prospect were also discussed. 

https://doi.org/10.1016/j.mtbio.2023.100579

Microneedles for in situ tissue regeneration

Design principles of microneedles for drug delivery and sampling applications

Medical implant-associated infections (IAI) is a growing threat to patients undergoing implantation surgery. IAI prevention typically relies on medical implants endowed with bactericidal properties achieved through surface modifications with antibiotics. However, the clinical efficacy of this traditional paradigm remains suboptimal, often necessitating revision surgery and posing potentially lethal consequences for patients. To bolster the existing anti-IAI arsenal, we propose herein a chitosan-based bioactive coating, i.e., ChitoAntibac, which exerts bacteria-inhibitory effects either through immune modulation or phage-directed microbial clearance, without relying on conventional antibiotics. The immuno-stimulating effects and phage-induced bactericidal properties can be tailored by engineering the loading dynamic of macrophage migration inhibitory factor (MIF), which polarizes macrophages towards the proinflammatory subtype (M1) with enhanced bacterial phagocytosis, and Staphylococcal Phage K, resulting in rapid and targeted pathogenic clearance (>99.99%) in less than 8 h. We posit that our innovative antibacterial coating opens a new avenue in the pursuit of effective IAI prevention through immuno-stimulation and phage therapeutics. 

Bioactive coating provides antimicrobial protection through immunomodulation and phage therapeutics

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Design principles of microneedles for drug delivery and sampling applications

Bioactive coating provides antimicrobial protection through immunomodulation and phage therapeutics