Search

Abstract There is a global trend of increasing antibiotic resistance to Gram‐negative bacteria and the medical research community is looking for alternative antibiotics. Antibiotics such as polymyxin B (PMB) show excellent efficacy and low resistance rates against Gram‐negative bacteria. The topical administration of PMB, however, has clinical limitations such as minimal residence time, making it difficult for its use to treat skin infections. Here, we present porous silicon microneedle (pSi MN) patches to deliver PMB to the skin. pSi MN patches are fabricated by, first, generating the projections by dry Si etching techniques, followed by an electrochemical etching to create porous layers around the MNs. After loading PMB into the porous layer, the antibacterial activity of pSi MNs is determined by measuring the inhibition zone of Gram‐negative Escherichia coli. Next, PMB is efficiently delivered into the epidermal layer of ex vivo skin models, as confirmed by chemical mapping using matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI‐MSI). The results demonstrate that pSi MN patches are an efficient and versatile tool for the transdermal delivery of PMB with maintained bioactivity and antimicrobial efficacy, thus expanding the possibilities of current transdermal drug delivery systems.

Abstract Microneedles (MNs) have emerged as a promising solution for drug delivery and extraction of body fluids. Pain is an important physiological attribute to be examined when designing MNs. There is no known representation of pain with geometric features of a MN despite the focus on experimental work. This study focuses on optimizing MN designs with the aim of minimizing pain through means of machine learning, finite element analysis, and optimization tools. Three distinct approaches are proposed. The first approach involves training multiple regression models on data obtained through finite element analysis in COMSOL. The second approach uses COMSOL's built‐in nonlinear optimization solver. Finally, the third approach utilizes the LiveLink interface between COMSOL and MATLAB, combined with Bayesian optimization. Each approach presents unique strengths and challenges, with the third approach demonstrating significant promise due to its efficiency, practicality, and time‐saving.

Microneedle array systems loaded with responsive nanoparticles have received increasing attention due to the advantages of good drug stability, targeting ability, controlled release of drugs, high bioavailability, painlessness, and good patient compliance. Compared with oral drug delivery, microneedle transdermal drug delivery eliminates the need to pass through the gastrointestinal tract and liver, reducing the metabolic consumption of drugs by first‐pass effect. While compared with intravenous drug delivery, microneedle transdermal drug delivery reduces patient discomfort and does not require professional administration. However, there are few review articles on microneedles loaded with responsive nanoparticles. Herein, the current researches on microneedles loaded with specific responsive nanoparticles such as glucose‐responsive, pH‐responsive, enzyme‐responsive, light‐responsive, magnetic‐responsive, ultrasound‐responsive, and multiresponsive, and the biomedical application of these microneedle array systems are summarized. In addition, the challenges and prospects of microneedle strategies loaded with responsive nanoparticles are briefly discussed, which will facilitate the development of such versatile drug‐delivery strategy.

Abstract Neutrophils play a key role in the innate immune inflammatory response, notably through the release of the myeloperoxidase enzyme from azurophilic granules, locally generating reactive oxygen species. Although short‐lived, these reactive oxygen species are directly involved in local tissue damage in response to microbial intrusion. Neutrophil‐derived myeloperoxidase has been reported as an important factor in the elicitation of atopic dermatitis and is considered a potential target and biomarker. This study describes the use of in situ imaging techniques comprising both chemiluminescent resonance energy‐transfer and ratiometric fluorescent microtattoos to locally and non‐invasively image myeloperoxidase activity and skin reactive oxygen species in a murine model of calcipotriol‐induced atopic dermatitis. Using neutrophil depletion to assess granulocyte contribution to the observed imaging signals, the non‐invasive longitudinal data are found to correlate with endpoint biochemical activity assays for both myeloperoxidase and reactive oxygen species by‐products, as well as with immunohistochemical analysis.

Abstract Although interstitial fluid (ISF) is recognized as an important source of biomarkers, it is difficult and time‐consuming to extract, thus limiting its use in medical diagnostic and clinical settings. An inexpensive and effective technique for accessing ISF could benefit people with various health conditions and offer platforms for on‐device sensing biomarkers. Microneedles (MNs) are minimally invasive devices that have gained extensive interest over recent decades. MNs can address some of the challenges associated with ISF extraction and sensing. Accessing ISF using MNs has the potential to develop advanced, non‐invasive point‐of‐care (POC) microdevices that enable detection or continuous monitoring within the dermal ISF, therefore drastically impacting the healthcare system. This review describes recent studies exploring MN devices for ISF sampling and sensing. Several extraction processes, sampling volume, sampling duration, integration with biosensors, sensing of biomarkers, and subsequent analysis of ISF are discussed in detail. Furthermore, opportunities, conclusions, and future prospects for developing new research in the field are also discussed.

Abstract Microneedles (MNs) are versatile tiny devices that have attracted interest in various fields including medicine, environment, food and agriculture due to their unique properties, such as low‐cost, simplicity, pain‐free application and minimally invasive penetration, therapeutic efficacy, biosensing ability, and biocompatibility. These properties along with the MNs distinctive geometry including dimension control, material type and fabrication techniques have enabled the optimization of MNs based on each desired application. This review summarizes the latest advances in MN‐based sensors in a variety of fields and provides a bird's eye view over the wide range of applications, starting from material and fabrication techniques to advanced sensor types in the biomedical and environmental fields for both sensing and treatment, and showing the profound advantages of this emerging tool in clinical and sustainable fields.

Microneedles are demonstrated as an effective strategy for chronic wound treatment. Great endeavors are devoted to developing microneedles with natural compositions and potent functions to promote therapeutic effects for wound healing. Herein, a novel graphene oxide-integrated methacrylated fish gelatin (GO-FGelMA) microneedle patch encapsulated with bacitracin and vascular endothelial growth factor (VEGF) is developed for chronic wound management. As the natural components and porous structures of FGelMA, the fabricated microneedle patches display satisfactory biocompatibility and drug-loading ability. Owing to the integration of graphene oxide, the microneedle patches can realize promoted drug release via near-infrared (NIR) irradiation. Besides, the encapsulated bacitracin and VEGF endow the microneedle patches with the ability to inhibit bacterial growth and promote angiogenesis. It is demonstrated that the GO-FGelMA microneedle patches with efficient drug release exert a positive influence on the wound healing process through reduced inflammation, enhanced wound closure, and improved tissue regeneration. Thus, it is believed that the proposed drugs-loaded GO-FGelMA microneedle patches will hold great potential in future chronic wound treatment., (© 2024 Wiley‐VCH GmbH.)

In this study, a novel customized corneal cross-linking (CXL) treatment is explored that utilizes microneedles (MNs) for targeted riboflavin (RF) administration prior to the CXL procedure. Unlike the conventional "one-size-fits-all" approach, this protocol offers an option for more precise and efficacious treatment. To simulate a customized corneal crosslinking technique, four distinct microneedle (MN) molds designs, including circular, semi-circular, annular and butterfly shaped, are crafted for loading an optimized RF-hyaluronic acid solution and for the subsequent fabrication of MN arrays with varying morphologies. These MNs can gently puncture the corneal epithelium while preserving the integrity of the underlying stromal layer. Following the application of these microneedles, RF solution is replenished to enhance the RF content within the stroma through the punctures created by the MNs, resulting in exceptional customized corneal cross-linking effects that are comparable to the conventional epi-off CXL protocol. Additionally, it flattened the corneal curvature within the treated zone and facilitated rapid postoperative recovery of corneal tissue. These findings suggest that the integration of customized microneedle RF delivery with corneal crosslinking technology represents a potential novel treatment modality, holding promise for the tailored treatment of corneal pathologies, and offering a more precise and efficient alternative to traditional methods., (© 2024 Wiley‐VCH GmbH.)

Using high-resolution 3D printing, a novel class of microneedle array patches (MAPs) is introduced, called latticed MAPs (L-MAPs). Unlike most MAPs which are composed of either solid structures or hollow needles, L-MAPs incorporate tapered struts that form hollow cells capable of trapping liquid droplets. The lattice structures can also be coated with traditional viscous coating formulations, enabling both liquid- and solid-state cargo delivery, on a single patch. Here, a library of 43 L-MAP designs is generated and in-silico modeling is used to down-select optimal geometries for further characterization. Compared to traditionally molded and solid-coated MAPs, L-MAPs can load more cargo with fewer needles per patch, enhancing cargo loading and drug delivery capabilities. Further, L-MAP cargo release kinetics into the skin can be tuned based on formulation and needle geometry. In this work, the utility of L-MAPs as a platform is demonstrated for the delivery of small molecules, mRNA lipid nanoparticles, and solid-state ovalbumin protein. In addition, the production of programmable L-MAPs is demonstrated with tunable cargo release profiles, enabled by combining needle geometries on a single patch., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Microneedle array patches (MAPs) are extensively studied for transdermal drug delivery. Additive manufacturing enables precise control over MAP customization and rapid fabrication. However, the scope of 3D-printable, bioresorbable materials is limited. Dexamethasone (DXM) is widely used to manage inflammation and pain, but its application is limited by systemic side effects. Thus, it is crucial to achieve high local drug concentrations while maintaining low serum levels. Here, poly(propylene fumarate-co-propylene succinate) oligomers are fabricated into DXM-loaded, bioresorbable MAPs via continuous liquid interface production 3D printing. Thiol-ene click chemistry yields MAPs with tailorable mechanical and degradation properties. DXM-loaded MAPs exhibit controlled elution of drug in vitro. Transdermal application of DXM-loaded MAPs in a murine tibial fracture model leads to substantial relief of postoperative pain. Pharmacokinetic analysis shows that MAP administration is able to control pain at a significantly lower dose than intravenous administration. This work expands the material properties of 3D-printed poly(propylene fumarate-co-propylene succinate) copolyesters and their use in drug delivery applications., (© 2024 Wiley‐VCH GmbH.)

Keratins, the most abundant proteins in human hair, are excellent hair nutrients for growth. However, the complex components of keratin extract hinder their mechanism investigation, and the pure recombinant keratin with poor solubility limited its hair growth promotion efficiency. Here, the water-soluble recombinant keratins (RKs) of K31 and K81 are rationally designed through QTY Code methodology, which are then used to fabricate the microneedles to study the effect of keratin on hair growth. Interestingly, it is discovered that more than 40% of the hair follicles (HFs) in the RK81 QTY group entered the anagen on day 12 and the diameter of new hair is 15.10 ± 2.45 µm, which significantly promoted growth and development of HFs and improved new hair quality compared to RK31 QTY . Water-soluble RKs significantly enhanced HFs activity and de novo regeneration of robust hairs compared to extract and minoxidil by upregulating the PI3K/AKT/Nf-κB signaling axis. These findings highlight the potential of designing solubilized recombinant keratins with distinct properties to improve therapeutical effects and open new avenues to designing keratin-based proteins., (© 2024 Wiley‐VCH GmbH.)

Diabetic wounds are characterized by the disruption and cessation of essential healing stages, which include hemostasis, inflammation, proliferation, and remodeling. However, traditional treatments for diabetic wounds concentrate on individual stages of the healing process. Herein, this study utilizes mask-mediated sequential polymerization and varied cross-linking techniques to develop dual-modular microneedles (MNs) with fast- and slow-module, exhibiting varying degradation rates tailored for the full spectrum of diabetic wound healing. First, MNs incorporating calcium ions and dopamine synergistically promote rapid hemostasis. Second, fast-module physically cross-linked MNs rapidly D-mannose/dopamine-enhanced tripolyphosphate-quaternized chitosan (mDTC) nanoparticles (NPs) loaded with microRNA-147 (miRNA-147) to manage inflammation and oxidative stress in diabetic wounds. Additionally, dopamine in these NPs enhances their internalization and safeguards miRNA-147 from oxidative stress and RNase degradation. Finally, slow-module chemically cross-linked MNs facilitate the continuous release of deferoxamine (DFO) and dopamine, accelerating angiogenesis and tissue regeneration during the proliferation and remodeling stages. Manganese/dopamine-enhanced calcium peroxide NPs within the MNs initiate a blast-like generation of oxygen bubbles, not only enhancing the delivery of miRNA-mDTC NPs and DFO but also alleviating tissue hypoxia. Consequently, dual-modular MNs are instrumental in promoting rapid and complete healing of diabetic wounds through all stages of healing., (© 2024 Wiley‐VCH GmbH.)

Acute wounds are converted to chronic wounds due to advanced age and diabetic complications. Nanozymes catalyze ROS production to kill bacteria without causing drug resistance, while microneedles (MNs) can break through the skin barrier to deliver drugs effectively. Nanozymes can be intergrateded into MNs delivery systems to improve painless drug delivery. It can also reduce the effective dose of drug sterilization while increasing delivery efficiency and effectively killing wounded bacteria while preventing drug resistance. This paper describes various types of metal nanozymes from previous studies and compares their mutual enhancement with nanozymes. The pooled results show that the MNs, through material innovation, are able to both penetrate the scab and deliver nanozymes and exert additional anti-inflammatory and bactericidal effects. The catalytic effect of some of the nanozymes can also accelerate the lysis of the MNs or create a cascade reaction against inflammation and infection. However, the issue of increased toxicity associated with skin penetration and clinical translation remains a challenge. This study reviews the latest published results and corresponding challenges associated with the use of MNs combined with nanozymes for the treatment of wounds, providing further information for future research., (© 2024 Wiley‐VCH GmbH.)

Continuous monitoring of clinically relevant biomarkers within the interstitial fluid (ISF) using microneedle (MN)-based assays, has the potential to transform healthcare. This study introduces the Wearable Aptalyzer, an integrated system fabricated by combining biocompatible hydrogel MN arrays for ISF extraction with an electrochemical aptamer-based biosensor for in situ monitoring of blood analytes. The use of aptamers enables continuous monitoring of a wide range of analytes, beyond what is possible with enzymatic monitoring. The Wearable Aptalyzer is used for real-time and multiplexed monitoring of glucose and lactate in ISF. Validation experiments using live mice and rat models of type 1 diabetes demonstrate strong correlation between the measurements collected from the Wearable Aptalyzer in ISF and those obtained from gold-standard techniques for blood glucose and lactate, for each analyte alone and in combination. The Wearable Aptalyzer effectively addresses the limitations inherent in enzymatic detection methods as well as solid MN biosensors and the need for reliable and multiplexed bioanalytical monitoring in vivo., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Several natural Chinese herbal medicines have demonstrated considerable potential in facilitating wound healing, while the primary concern remains centered around optimizing formulation and structure to maximize their efficacy. To address this, a natural microneedles drug delivery system is proposed that harnesses gelatinized starch and key Chinese herbal ingredients-aloe vera and berberine. After gelatinized and aged in a well-designed mold, the starch-based microneedles are fabricated with suitable mechanical strength to load components. The resulting Chinese herbal hydrogel microneedles, enriched with integrated berberine and aloe, exhibit antibacterial, anti-inflammatory, and fibroblast growth-promoting properties, thereby facilitating wound healing in the whole process. In vivo experimental results underscore the notable achievements of the microneedles in early-stage antibacterial effects and subsequent tissue reconstruction, contributing significantly to the overall wound healing process. These results emphasize the advantageous combination of traditional Chinese medicine with microneedles, presenting a novel strategy for wound repair and opening new avenues for the application of traditional Chinese medicine., (© 2024 Wiley‐VCH GmbH.)

Bacteria-induced keratitis is a major cause of corneal blindness in both developed and developing countries. Instillation of antibiotic eyedrops is the most common management of bacterial keratitis but usually suffers from low bioavailability (i.e., <5%) and frequent administration, due to the existence of corneal epithelial barrier that prevents large and hydrophilic drug molecules from entering the cornea, and the tear film on corneal surface that rapidly washes drug away from the cornea. Here, a self-implantable core-shell microneedle (MN) patch with programmed drug release property to facilitate bacterial keratitis treatment is reported. The pH-responsive antimicrobial nanoparticles (NPs), Ag@ZIF-8, which are capable of producing antibacterial metal ions in the infected cornea and generating oxidative stress in bacteria, are loaded in the dissolvable core, while the anti-angiogenic drug, rapamycin (Rapa), is encapsulated in the biodegradable shell, thereby enabling rapid release of Ag@ZIF-8 NPs and sustained release of Rapa after corneal insertion. Owing to the programmed release feature, one single administration of the core-shell MN patch in a rat model of bacterial keratitis, can achieve satisfactory antimicrobial activity and superior anti-angiogenic and anti-inflammation effects as compared to daily topical eyedrops, indicating a great potential for the infectious keratitis therapy in clinics., (© 2024 Wiley‐VCH GmbH.)

Wearable bioelectronics represents a significant breakthrough in healthcare settings, particularly in (bio)sensing which offers an alternative way to track individual health for diagnostics and therapy. However, there has been no notable improvement in the field of cancer, particularly for skin cancer. Here, a wearable bioelectronic patch is established for transdermal sensing of the melanoma biomarker, tyrosinase (Tyr), using a microneedle array integrated with a surface-bound chemo-responsive smart probe to enable target-specific electrochemical detection of Tyr directly from human skin tissue. The results presented herein demonstrate the feasibility of a transdermal microneedle sensor for direct quantification of enzyme biomarkers in an ex vivo skin model. Initial performance analysis of the transdermal microneedle sensor proves that the designed methodology can be an alternative for fast and reliable diagnosis of melanoma and the evaluation of skin moles. The innovative approach presented here may revolutionize the landscape of skin monitoring by offering a nondisruptive means for continuous surveillance and timely intervention of skin anomalies, such as inflammatory skin diseases or allergies and can be extended to the screening of multiple responses of complementary biomarkers with simple modification in device design., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Transdermal biosensing focuses on the qualitative and quantitative collection and detection of biomarkers on and in the skin layers. In comparison to the blood‐based diagnosis, transdermal sensing technologies provide pain‐free, convenient, patient‐friendly, and infection‐avoiding methods to collect biosignals from transdermal samples such as interstitial fluid (ISF) and sweat. This article summarizes the latest trends in transdermal biosensing including the technologies and their application blueprints. Specifically, the current transdermal biosensing technologies including microneedles, microfluidics, and reverse iontophoresis are introduced first. Subsequently, their roles in daily health status monitoring, disease diagnosis and therapy monitoring are discussed in detail. Finally, an overview of the future blueprints and application prospects of transdermal biosensing is provided.

Many types of microneedle (MN) arrays have been tested for delivery of vaccines to the skin. However, the effect of MN geometry/array design on antibody production is still unclear. Reports suggest that systemic immune responses may be affected by how MN arrays “mechanically” deliver vaccines, which can induce cell damage and act as an adjuvant. This includes parameters such as MN length/insertion depth, delivery energy/velocity, MN shape, and density. However, these effects have not been systematically investigated. Herein, the effect of MN density on antibody responses to influenza vaccination is assessed, keeping all other variables constant. MN arrays are manufactured within the “high‐density range” from 5 k microneedles cm−2 (n cm−2) to the “ultrahigh” 30 k n cm−2. Prior to this study, the highest MN density used for vaccination is 20 k n cm−2. Thus, MN array vaccination is evaluated over an unprecedented range. Cell viability is assessed in the skin after application and antibody responses at days 21/63. It is demonstrated that increasing MN density from 5 to 30 k n cm−2 increases both epidermal cell death and anti‐influenza IgG1, without an increase in anti‐influenza IgG2a. This suggests that MN density has a direct adjuvant effect on immune responses through Th2‐mediated signalling—a response critical for human vaccination.

Interstitial fluid (ISF) is an attractive alternative to regular blood sampling for health checks and disease diagnosis. Porous microneedles (MNs) are well suited for collecting ISF in a minimally invasive manner. However, traditional methods of molding MNs from microfabricated templates involve prohibitive fabrication costs and fixed designs. To overcome these limitations, this study presents a facile and economical additive manufacturing approach to create porous MNs. Compared to traditional layerwise build sequences, direct ink drawing with nanocomposite inks can define sharp MNs with tailored shapes and achieve vastly improved fabrication efficiency. The key to this fabrication strategy is the yield-stress fluid ink that is easily formulated by dispersing silica nanoparticles into the cellulose acetate polymer solution. As-printed MNs are solidified into interconnected porous microstructure inside a coagulation bath of deionized water. The resulting MNs exhibit high mechanical strength and high porosity. This approach also allows porous MNs to be easily integrated on various substrates. In particular, MNs on filter paper substrates are highly flexible to rapidly collect ISF on non-flat skin sites. The extracted ISF is used for quantitative analysis of biomarkers, including glucose, = calcium ions, and calcium ions. Overall, the developments allow facile fabrication of porous MNs for transdermal diagnosis and therapy., (© 2024 Wiley‐VCH GmbH.)

Microneedles (MNs) have maintained their popularity in therapeutic and diagnostic medical applications throughout the past decade. MNs are originally designed to gently puncture the stratum corneum layer of the skin and have lately evolved into intelligent devices with functions including bodily fluid extraction, biosensing, and drug administration. MNs offer limited invasiveness, ease of application, and minimal discomfort. Initially manufactured solely from metals, MNs are now available in polymer-based varieties. MNs can be used to create systems that deliver drugs and chemicals uniformly, collect bodily fluids, and are stimulus-sensitive. Although these advancements are favorable in terms of biocompatibility and production costs, they are insufficient for the therapeutic use of MNs. This is the first comprehensive review that discusses individual MN functions toward the evolution and development of smart and multifunctional MNs for a variety of novel and impactful future applications. The study examines fabrication techniques, application purposes, and experimental details of MN constructs that perform multiple functions concurrently, including sensing, drug-molecule release, sampling, and remote communication capabilities. It is highly likely that in the near future, MN-based smart devices will be a useful and important component of standard medical practice for different applications., (© 2024 The Authors. Small published by Wiley‐VCH GmbH.)

Sustained inflammation can halt or delay wound healing, and macrophages play a central role in wound healing. Inflammatory macrophages are responsible for the removal of pathogens, debris, and neutrophils, while anti-inflammatory macrophages stimulate various regenerative processes. Recombinant human Proteoglycan 4 (rhPRG4) is shown to modulate macrophage polarization and to prevent fibrosis and scarring in ear wound healing. Here, dissolvable microneedle arrays (MNAs) carrying rhPRG4 are engineered for the treatment of skin wounds. The in vitro experiments suggest that rhPRG4 modulates the inflammatory function of bone marrow-derived macrophages. Degradable and detachable microneedles are developed from gelatin methacryloyl (GelMA) attach to a dissolvable gelatin backing. The developed MNAs are able to deliver a high dose of rhPRG4 through the dissolution of the gelatin backing post-injury, while the GelMA microneedles sustain rhPRG4 bioavailability over the course of treatment. In vivo results in a murine model of full-thickness wounds with impaired healing confirm a decrease in inflammatory biomarkers such as TNF-α and IL-6, and an increase in angiogenesis and collagen deposition. Collectively, these results demonstrate rhPRG4-incorporating MNA is a promising platform in skin wound healing applications., (© 2024 Wiley‐VCH GmbH.)

Hair loss is characterized by the inability of hair follicles (HFs) to enter the telogen-anagen transition (TAT) and lack of de novo HFs. Current pharmaceutical therapies and surgical modalities have been largely limited to regulating hair regrowth efficiently without side effects and lacking treatment compliance. Here, this work proposes a materiobiomodulation therapy (MBMT), wherein polydopamine (PDA) nanoparticles with redox activity can be modulated to have a stoichiometric ROS (H 2 O 2 ) donating ability. These nanoparticles can intracellularly deliver ROS with high-efficiency via the clathrin-dependent endocytosis process. Utilizing homozygote transgenic HyPerion (a genetically-encoded H 2 O 2 biosensor) mice, this work also achieves in vivo dynamic monitoring of intracellular H 2 O 2 elevation induced by ROS donators. Subcutaneous administration with ROS donators results in rapid onset of TAT and subsequent hair regrowth with a specific ROS "hormesis effect." Mechanistically, ROS activate β-catenin-dependent Wnt signaling, upregulating hair follicle stem cell expression. This work further develops a microneedles patch for transdermal ROS delivery, demonstrating long-term, low-dose ROS release. Unlike photobiomodulation therapy (PBMT), MBMT requires no external stimuli, providing a convenient and efficient approach for clinical hair loss treatment. This material-HF communication implicates new avenues in HF-related diseases, achieving targeted ROS delivery with minimal side effects., (© 2024 Wiley‐VCH GmbH.)

Senile wound healing risks a variety of health complications and makes both economic and psychological burdens on patients greatly. Poor activity of aged dermal fibroblasts (A-FBs) and local disordered immunoreaction in the deep dermis contribute to delayed wound healing. Therefore, the locally complex microenvironment in deep requires additional processing. Herein, a novel double-layer hyaluronic acid methacrylate (HAMA)/polyvinyl alcohol (PVA) microneedle patch (MNP) coated by young fibroblast-derived exosomes (Y-EXOs) (Y-EXOs@HAMA/PVA MNP) is presented for deep drug delivery, aged wound healing and immunoregulation. A spraying and freeze-drying method is applied for keeping the bioactivity of the nanovesicles. An ideal loading of Y-EXOs and enhanced strength for penetration have realized after circulation for times. The Y-EXOs@HAMA/PVA MNP shows an excellent influence on delayed wound healing of aged skin with active A-FBs, more deposition of collagen and less production of IL-17A compared with application of aged fibroblast-derived exosomes (A-EXOs). Moreover, the content microRNAs in Y-EXOs and A-EXOs are sequenced for further study. This study initiatively demonstrates that Y-EXOs have effective function on both anti-aging and anti-inflammation and Y-EXOs@HAMA/PVA MNP is expected as a novel strategy for deep drug delivery for promoting hard wound healing in aged skin in future clinical application., (© 2024 Wiley‐VCH GmbH.)

Type 2 diabetes is rapidly emerging as a global public health problem. While blood glucose monitoring has been the primary method of managing diabetes for decades, the increasing global prevalence of the disease suggests that there might be a need to identify additional biomarkers for a more precise early diagnosis. Herein, a microneedle patch based wearable sensor is developed for the purpose of diabetic diagnosis. Utilizing methacrylic acid modified gelatin and polyvinyl alcohol in the fabrication of microneedles has improved their mechanical properties for skin penetration and increased swelling capacity for interstitial fluid extraction, thanks to the double crosslinking mechanism. The fabricated microneedles are further integrated with test paper functionalized with enzyme and dye molecules to detect multiple signature biomarkers of diabetes in vivo through a colorimetric reaction. Such a wearable microneedle patch  holds significant promise for the real-time monitoring of various biomarkers related to chronic diseases and aging., (© 2024 Wiley‐VCH GmbH.)

Sustained-release drug delivery formulations are preferable for treating various diseases as they enhance and prolong efficacy, minimize adverse effects, and avoid frequent dosing. However, these formulations are associated with poor patient compliance, require trained personnel for administration, and involve harsh manufacturing conditions that compromise drug stability. Here, a self-healing biodegradable porous microneedle (PMN) patch is reported for sustained drug delivery. The PMN patch is fabricated by a cryogenic micromoulding followed by phase separation, leading to formation of interconnected pores on the surface and internals of MNs. The pores with self-healing feature enable the PMNs to load hydrophilic drugs with different molecular weights in a mild and efficient manner. The healed PMNs can easily penetrate into the skin under press and detach from the supporting substrate under shear, thereby acting as implantable drug reservoirs for achieving sustained release of drugs for at least 40 days. One-time administration of desired therapeutics using the sustained-release healed PMNs resulted in stronger and longer-lasting efficacy in mitigating psoriasis and eliciting immunity compared to conventional methods with multiple administrations. The self-healing PMN patch for self-administrated and long-acting drug delivery can eventually improve medication adherence in prophylactic and therapeutic protocols that typically require frequent dosages., (© 2023 Wiley‐VCH GmbH.)

Transdermal delivery is an attractive delivery method that increases bioavailability, is suitable for a wide variety of therapeutics, and offers stable delivery outcomes. However, many therapeutics are unable to readily cross the stratum corneum. Microneedles mechanically disrupt the cutaneous barrier to deliver small molecules, proteins, and vaccines. To date, microneedles have not been used in conjunction with coacervate, a liquid-liquid phase separation that protects unstable proteins. A three-layer microneedle for the controlled release of three different molecules is designed. Through micromolding, microneedles are efficiently generated, which benefits product scalability. The microneedles have good mechanical integrity and effectively penetrate porcine skin ex vivo. The three layers, in the microneedles, release the cargo in a three-phase manner. The released protein maintains its structure well. Moreover, layer thickness can be controlled by varying fabrication parameters. The microneedles can incorporate both small molecule drugs and protein therapeutics, thus promising uses in multi-drug therapies through a single treatment., (© 2023 Wiley‐VCH GmbH.)

Effective treatment of deep-seated tumors relies on enhanced drug penetration in transdermal drug delivery systems. While microneedles (MNs) and iontophoresis techniques have shown improved transdermal drug delivery efficiency, challenges such as skin elasticity, high electrical resistance of the stratum corneum, and external power supply requirements hinder their efficacy in treating deep-seated tumors. In this study, a wearable, self-powered MN patch that integrates a flexible triboelectric nanogenerator (F-TENG) is presented, aimed at advancing deep-seated tumor therapy. MNs are composed of water-soluble materials mixed with negatively charged pH-responsive nanoparticles (NPs) loaded with therapeutic drugs. The F-TENG harnesses personal mechanical movements generate electrical energy. Leveraging the advantages of both MNs and F-TENG, therapeutic NPs can penetrate deep skin locations upon MN patch insertion, releasing drugs rapidly in acidic tumor tissues. Owing to these features, a single administration of the integrated MN-patch in a mouse model with deep-seated melanoma exhibits superior therapeutic efficacy in inhibiting deep-located tumor compared to using the MN-patch alone, indicating promising potential for treating tumors at deep sites., (© 2023 Wiley-VCH GmbH.)

The treatment of chronic wounds still presents great challenges due to being infected by biofilms and the damaged healing process. The current treatments do not address the needs of chronic wounds. In this study, a highly effective dressing (Dox-DFO@MN Hy) for the treatment of chronic wounds is described. This dressing combines the advantages of microneedles (MNs) and hydrogels in the treatment of chronic wounds. MNs is employed to debride the biofilms and break down the wound barrier, providing rapid access to therapeutic drugs from hydrogel backing layer. Importantly, to kill the pathogenic bacteria in the biofilms specifically, Doxycycline hydrochloride (Dox) is wrapped into the polycaprolactone (PCL) microspheres that have lipase-responsive properties and loaded into the tips of MNs. At the same time, hydrogel backing layer is used to seal the wound and accelerate wound healing. Benefiting from the combination of two advantages of MNs and hydrogel, the dressing significantly reduces the bacteria in the biofilms and effectively promotes angiogenesis and cell migration in vitro. Overall, Dox-DFO@MN Hy can effectively treat chronic wounds infected with biofilms, providing a new idea for the treatment of chronic wounds., (© 2023 Wiley‐VCH GmbH.)

Point-of-care (POC) has the capacity to support low-cost, accurate and real-time actionable diagnostic data. Microneedle sensors have received considerable attention as an emerging technique to evolve blood-based diagnostics owing to their direct and painless access to a rich source of biomarkers from interstitial fluid. This review systematically summarizes the recent innovations in microneedle sensors with a particular focus on their utility in POC diagnostics and personalized medicine. The integration of various sensing techniques, mostly electrochemical and optical sensing, has been established in diverse architectures of "lab-on-a-microneedle" platforms. Microneedle sensors with tailored geometries, mechanical flexibility, and biocompatibility are constructed with a variety of materials and fabrication methods. Microneedles categorized into four types: metals, inorganics, polymers, and hydrogels, have been elaborated with state-of-the-art bioengineering strategies for minimally invasive, continuous, and multiplexed sensing. Microneedle sensors have been employed to detect a wide range of biomarkers from electrolytes, metabolites, polysaccharides, nucleic acids, proteins to drugs. Insightful perspectives are outlined from biofluid, microneedles, biosensors, POC devices, and theragnostic instruments, which depict a bright future of the upcoming personalized and intelligent health management., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

In recent years, microneedles (MNs) have attracted a lot of attention due to their microscale sizes and high surface area (500-1000 µm in length), allowing pain-free and efficient drug delivery through the skin. In addition to the great success of MNs based transdermal drug delivery, especially for skin diseases, increasing studies have indicated the expansion of MNs to diverse nontransdermal applications, including the delivery of therapeutics for hair loss, ocular diseases, and oral mucosal. Here, the current treatment of hair loss, eye diseases, and oral disease is discussed and an overview of recent advances in the application of MNs is provided for these three noncutaneous localized organ diseases. Particular emphasis is laid on the future trend of MNs technology development and future challenges of expanding the generalizability of MNs., (© 2023 Wiley-VCH GmbH.)

Microneedles have emerged as a promising platform for transdermal drug delivery with prominent advantages, such as enhanced permeability, mitigated pain, and improved patient adherence. While microneedles have primarily been employed for delivering small molecules, nucleic acids, peptides, and proteins, recent researches have demonstrated their prospect in combination with cell therapy. Cell therapy involving administration or transplantation of living cells (e.g. T cells, stem cells, and pancreatic cells) has gained significant attention in preclinical and clinical applications for various disease treatments. However, the effectiveness of systemic cell delivery may be restricted in localized conditions like solid tumors and skin disorders due to limited penetration and accumulation into the lesions. In this perspective, an overview of recent advances in microneedle-assisted cell delivery for immunotherapy, tissue regeneration, and hormone modulation, with respect to their mechanical property, cell loading capacity, as well as viability and bioactivity of the loaded cells is provided. Potential challenges and future perspectives with microneedle-mediated cell therapy are also discussed., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The advancement and extensive demand for transdermal therapies can benefit from a safe, and efficient and user-friendly transdermal technology with broad applicability in delivering various hydrophilic drugs. Here the design and proof of concept applications of an ultraswelling microneedle device that enables the facile and efficient loading and transdermal delivery of hydrophilic drugs with different molecular weights is reported. The device consists of a super-hydrophilic hydrogel microneedle array and a resin base substrate. Using a special micromolding technique that involves hydrated crosslinking and cryogenic-demolding, the microneedle part displays a rapid swelling ratio of ≈3800%, enabling the loading of drugs up to 500 kDa in molecular weight. The drug loading process using the device just involves incubating the microneedle part in a drug solution for 1 min, followed by 15 min of drying. The microneedles can easily penetrate the skin under press and detach from the base substrate under shear, thereby releasing the payload. Administration of desired therapeutic agents using the device outperformed conventional administration methods in mitigating psoriasis and eliciting immunity. This biocompatible device, capable of withstanding ethylene oxide sterilization, can enhance the efficacy and accessibility of transdermal therapies in research institutes, hospitals, and even home settings., (© 2023 Wiley-VCH GmbH.)

Intervertebral disc degeneration (IVDD) is a global public health issue. The injury of annulus fibrosus (AF) caused by acupuncture or discectomy can trigger IVDD again. However, there is currently no suitable method for treating AF injury. In this study, the high-strength smart microneedles (MNs) which can penetrate the AF tissue through a local and minimally invasive method, and achieve remote control of speeded-up release of the drug and hyperthermia by the Near Infrared is developed. The PDA/GelMA composite MNs loaded with diclofenac sodium are designed to extracellularly "offend" the inflammatory microenvironment and mitigate damage to cells, and intracellularly increase the level of cytoprotective heat shock proteins to enhance the defense against the hostile microenvironment, achieving "offensive and defensive" effects. In vitro experiments demonstrate that the synergistic treatment of photothermal therapy and anti-inflammation effectively reduces inflammation, inhibits cell apoptosis, and promotes the synthesis of the extracellular matrix (ECM). In vivo experiments show that the MNs mitigate the inflammatory response, promote ECM deposition, reduce the level of apoptosis, and restore the biomechanical properties of the intervertebral disc (IVD) in rats. Overall, this high-strength smart MNs display promising "offensive and defensive" effects that can provide a new strategy for IVD repair., (© 2023 Wiley-VCH GmbH.)

Applying antibacterial polymers and pro-regenerative small molecules are two individual strategies for accelerating wound healing. However, integrating those two unique approaches into one therapeutic platform that meets clinical requirements is still a challenge. Herein, a series of antibacterial gelatin methacrylate (GelMA)/ε-polylysine (ε-PL) composite hydrogels (termed as GP-n HGs, n = 0, 10, 20, and 30, respectively) are innovatively fabricated by ultraviolet light (UV) crosslinking. The GP-n HGs are proved to be broad-spectrum antibacterial and biocompatible. Among those GP-n HGs, the GP-20 HG is selectively processed into microneedle following a mold-casting method. Then, the glabridin is loaded into those needles to produce composite microneedle termed GP-20@Gla MN. An S. aureus-infected full-thickness defect model in rats is created to evaluate the wound-healing effect of GP-20@Gla MN. Furthermore, an RNA sequencing assay is performed to explore the possible molecular mechanisms of glabridin in promoting tissue regeneration, and many positive routes are summarized. This work is of significant novelty in fulfilling complex clinical needs by simultaneously optimizing the advanced microneedles' chemical compositions and physical structures. This work will provide a promising therapeutic platform for treating infected and chronic wounds., (© 2023 Wiley-VCH GmbH.)

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., (© 2023 Wiley-VCH GmbH.)

In this paper, a roadmap is provided for the regulatory approval of one of the exciting and dynamic drug delivery fields, microneedles, by using a Quality by Design approach to pharmaceutical product development. In this regard, a quality target product profile (QTPP) and the critical quality attributes (CQA) of microneedles are identified. A case study of the recently patented method of fabricating glass microneedles entirely from a therapeutic agent, thus eliminating the requirement for additional excipients is discussed. The glass microneedle, ArrayPatch, is a propriety wearable device with platform potential consisting of an array of sharp, but painless, dissolvable microneedles manufactured with 100% drug. The microneedles penetrate the skin on application and dissolve to deliver a locally effective dose. The in vitro characterization of the microneedle CQAs under WHO-guided stability conditions will be described to assess the manufacturing readiness of ArrayPatch.  A live technical video is also provided, presenting a unique procedure of jugular vein cannulation through the ear vein of a pig animal model to study the in vivo pharmacokinetics of ArrayPatch compared to standard-of-care marketed products., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

The stratum corneum (SC) and cell membrane are two major barriers that hinder the therapeutic outcomes of transdermal drug delivery for the treatment of skin diseases. While microneedles (MNs) can efficiently penetrate the SC to deliver nanomedicines, the optimization of physicochemical properties of nanomedicines in MNs to enhance their in vivo cellular delivery efficiency remains unclear. Here, how the size and surface charge of drug-loaded liposomes in MNs influence the retention time and cellular delivery in psoriatic skin is systematically investigated. The results indicate that while 100 nm negatively-charged liposomes in MNs show higher cellular uptake in vitro, 250 and 450 nm liposomes could enhance skin retention and the long-term in vivo cellular delivery efficiency of drugs. Moreover, 250 nm cationic liposomes with a stronger positive charge show an extraordinarily long skin retention time of 132 h and significantly higher in vivo cellular internalization. In the treatment study, dexamethasone (dex)-loaded cationic liposomes-integrated MNs show better therapeutic outcomes than dex-loaded anionic liposomes-integrated MNs in a psoriasis-like animal model. The design principles of liposomes in MN drug delivery systems explored in the study hold the potential for enhancing the therapeutic outcomes of psoriasis and are instrumental for successful translation., (© 2023 Wiley-VCH GmbH.)

Microneedles are a promising transdermal drug delivery system that has the advantages of minimal invasiveness, painlessness, and on-demand drug delivery compared with commonly used medical techniques. Natural resources are developed as next-generation materials for microneedles with varying degrees of success. Among them, silk fibroin is a natural polymer obtained from silkworms with good biocompatibility, high hardness, and controllable biodegradability. These properties provide many opportunities for integrating silk fibroin with implantable microneedle systems. In this review, the research progress of silk fibroin microneedles in recent years is summarized, including their materials, processing technology, detection, drug release methods, and applications. Besides, the research and development of silk fibroin in a multidimensional way are analyzed. Finally, it is expected that silk fibroin microneedles will have excellent development prospects in various fields., (© 2023 Wiley-VCH GmbH.)

Subcutaneous (SC) injection is a common administration route for rapid and efficient delivery of biotherapeutics. However, syringe-based injections usually require professional assistance and are associated with pain and potential risks of infections, thus leading to undesired patient compliance and poor life quality. Herein, this work presents an ultrarapid-acting microneedle (URA-MN) patch for immediate transdermal delivery of therapeutics in a minimally invasive manner. Effervescent agents are incorporated into the tip of URA-MN for rapid generation of CO 2 bubbles upon insertion into the skin, immediately powering the biotherapeutics release within a few minutes. The release kinetics of diverse agents including liraglutide (LRT), insulin, and heparin from the URA-MN patches are evaluated in three different mouse models, and the rapid release of biotherapeutics and potent therapeutic effects are achieved with only 5 min administration. Noteworthily, attributed to the short application duration and negligible residuals of MN matrix remaining in the skin, the URA-MN patch shows desirable biocompatibility after six-week administration., (© 2023 Wiley-VCH GmbH.)

As point-of-care testing (POCT) is becoming the new paradigm of medical diagnostics, there is a growing need to develop reliable POCT devices that can be conveniently operated in a minimally invasive manner. However, the clinical potential of POCT diagnostics is yet to be realized, mainly due to the limited and inconsistent amount of collected samples on these devices, undermining their accuracy. This study proposes a new biosensing platform modified with a functional polysuccinimide (PSI)-silica nanoparticle (SNP) composite system that can substantially increase the protein conjugation efficiency by modulating physicochemical interaction with proteins by several hundred percent from an unmodified device. The efficacy of this PSI-SNP system is further validated by applying it on the surface of a microneedle array (MN), which has emerged as a promising POCT device capable of accessing interstitial fluid through minimal penetration of the skin. This PSI-SNP MN is demonstrated to detect a wide array of proteins with high sensitivity on par with conventional whole serum analysis, validated by in vivo animal testing, effectively displaying broad applicability in biomedical engineering., (© 2023 Wiley-VCH GmbH.)

Wound healing, especially chronic wounds, has been one of the major challenges in the field of biomedicine. Drug therapy alone is not effective, so a variety of functional wound healing dressings have been developed. Microneedles have attracted more and more attentions in the field of wound healing dressings due to their penetration and high drug delivery efficiency. In this review, all the studies on the application of microneedles in wound healing in recent years are summarized, classify different microneedles according to their functions in the process of wound healing, discuss the current challenges in the transformation of microneedle technology toward clinical applications, and finally look forward to the future design and development directions of microneedles in this field., (© 2023 Wiley-VCH GmbH.)

Efforts aimed at exploring economical and efficient vaccination have taken center stage to combat frequent epidemics worldwide. Various vaccines have been developed for infectious diseases, among which nucleic acid vaccines have attracted much attention from researchers due to their design flexibility and wide application. However, the lack of an efficient delivery system considerably limits the clinical translation of nucleic acid vaccines. As mass vaccinations via syringes are limited by low patient compliance and high costs, microneedles (MNs), which can achieve painless, cost-effective, and efficient drug delivery, can provide an ideal vaccination strategy. The MNs can break through the stratum corneum barrier in the skin and deliver vaccines to the immune cell-rich epidermis and dermis. In addition, the feasibility of MN-mediated vaccination is demonstrated in both preclinical and clinical studies and has tremendous potential for the delivery of nucleic acid vaccines. In this work, the current status of research on MN vaccines is reviewed. Moreover, the improvements of MN-mediated nucleic acid vaccination are summarized and the challenges of its clinical translation in the future are discussed., (© 2023 Wiley-VCH GmbH.)

Reactive oxygen species (ROS)-mediated biological catalysis involves serial programmed enzymatic reactions and plays an important part against infectious diseases; while the spatiotemporal control of catalytic treatment to break the limitations of the disease microenvironment is challenging. Here, a novel spatiotemporal catalytic microneedles patch (CMSP-MNs) integrated with dual-effective Cu 2 MoS 4 (CMS) and polydopamine (PDA) nanoparticles (NPs) for breaking microenvironment restrictions to treat wound infections is designed. Since CMS NPs are loaded in the needles, CMSP-MNs can catalytically generate diverse ROS to cause effective bacterial inactivation during bacterial infection process. Besides, PDA NPs are encapsulated in the backing layer, which facilitate ROS elimination and oxygen production for solving hypoxic problems in wound microenvironment and alleviating the expression of inflammatory factors during the inflammation process. Based on these features, it is demonstrated through cell and animal experiments that these nanozymes-integrated MNs patches can realize selective regulation of ROS level with bacterial inactivation and inflammatory treatment, resulting in minimized side effects of over-production ROS and effective anti-infected treatment. It is believed that the presented MNs can provide a new therapeutic strategy with spatiotemporal adjustable catalytic properties in biomedical areas., (© 2023 Wiley-VCH GmbH.)

Microneedles (MNs) have become versatile platforms for minimally invasive transdermal drug delivery devices. However, there are concerns about MN-induced skin infections with long-term transdermal administration. Using the Langmuir-Blodgett (LB) technique, a simple method for depositing antibacterial nanoparticles of various shapes, sizes, and compositions onto MNs is developed. This strategy has merits over conventional dip coating techniques, including controlled coating layers, uniform and high coverage, and a straightforward fabrication process. This provides MNs with a fast-acting and long-lasting antibacterial effect. This study demonstrates that antibacterial MNs achieve superior bacterial elimination in vitro and in vivo without sacrificing payload capacity, drug release, or mechanical strength. It is believed that such a functional nanoparticle coating technique offers a platform for the expansion of MNs function, especially in long-term transdermal drug delivery fields., (© 2023 Wiley-VCH GmbH.)

Chronic nonhealing diabetic wounds are a serious complication of diabetes, with a high morbidity rate that can cause disability or death. The long period of inflammation and dysfunctional angiogenesis are the main reasons for wound-healing difficulty in diabetes. In this study, a multifunctional double-layer microneedle (DMN) is constructed to control infection and promote angiogenesis, meeting the multiple demands of the healing process of a diabetic wound. The double-layer microneedle is consisted in a hyaluronic acid substrate and a mixture of carboxymethyl chitosan and gelatin as the tip. The antibacterial drug tetracycline hydrochloride (TH) is loaded into the substrate of the microneedle to achieve rapid sterilization and promote resistance to external bacterial infections. The microneedle tip loaded with recombinant human epidermal growth factor (rh-EGF) is inserted into the skin, in response to gelatinase produced by resident microbe and disassociate to achieve the enzymatic response release. The double-layer drug-loaded microneedles (DMN@TH/rh-EGF) have antibacterial and antioxidant effects, and promote cell migration and angiogenesis in vitro. In an in vivo diabetic wound model, using rats, the DMN@TH/rh-EGF patch is able to inhibit inflammation, promote angiogenesis, collagen deposition, and tissue regeneration during the wound healing process, promoting its healing., (© 2023 Wiley-VCH GmbH.)

A cytokine storm may be the last attack of various diseases, such as sepsis, cancer, and coronavirus disease 2019, that can be life threatening. Real-time monitoring of cytokines in vivo is helpful for assessing the immune status of patients and providing an early warning of a cytokine storm. In this study, a functional carbon nanotube biointerface-based wearable microneedle patches for real-time monitoring of a cytokine storm in vivo via electrochemical analysis are reported. This wearable system has sensitivity with a detection limit of 0.54 pg mL -1 , high specificity, and 5 days of stability with a coefficient of variation of 4.0%. The system also has a quick response of several hours (1-4 h) to increasing cytokines. This wearable microneedle patch may offer a promising route for real-time biomolecule wearables construction. The patch is also the first reported integrated capture and monitoring system that is capable of real-time measurement of protein markers in interstitial fluid., (© 2023 Wiley-VCH GmbH.)

Chronic wound healing is a major challenge in biomedicine. Conventional therapies are usually associated with poor drug permeability, low bioavailability, risk of antimicrobial resistance, and require frequent administration. Therefore, a novel formulation with reduced antibiotic dosage, improved drug delivery efficiency, and low application frequency is of remarkable interest for chronic wound healing. Herein, a multifunctional microneedle (MN) patch is presented to achieve rapid wound healing via efficient chemo-photodynamic antibacterial effect and sustained release of growth factors at the wound bed. When the MN patch pierces the skin, MN tips carrying both low dosage of antibiotics and bioactive small molecule-encapsulated metal-organic frameworks (MOFs) rapidly dissolve and subsequently deliver the payloads to the wound. Upon light irradiation, MOF-based nanoparticles robustly convert O 2 into 1 O 2 , which acts synergistically with chemotherapy to remove pathogenic bacteria from the wound, exhibiting excellent chemo-photodynamic antibacterial performance with a tenfold reduction in the required antibiotic amount. The nanoparticles can achieve a continuous release of growth factors in the wound tissue, promoting the formation of epithelial tissue and neovascularization, thereby further accelerating chronic wound healing. Collectively, the designed multifunctional MOF-based MN patches offer a simple, safe, and effective alternative for chronic wound management., (© 2023 Wiley-VCH GmbH.)

Wound dressing patches based on stem cells have demonstrated promising potential in the treatment of diabetic wounds, while their capabilities in the maintenance of cell stemness, effective exchange of cellular substance, and precise targeting of the stem cells remain to be promoted. Here, a novel stem cell spheroid loaded microneedle (MN@SPs) patch is presented using microfluidic templating technology. By leveraging the precise fluid manipulation capabilities of the microfluidic template, stem cell spheroids (SPs) with uniform size can be generated in situ. The resulting SPs exhibit advanced viability and cell functions, as evidenced by the overexpressed genes related to extracellular matrix organization and angiogenesis. By loading these SPs into the microneedles (MNs), the platform enables the precise delivery and exchange of multiple active substances, which contribute to advanced neovascularization, collagen deposition, and tissue reconstruction of diabetic wounds. Overall, this microfluidic-engineered stem cell therapy platform demonstrates significant promise in promoting wound healing., (© 2023 Wiley-VCH GmbH.)

This work reports a portable, origami-type paper device with a plasmonic fluor-labeled microneedle sensing module for the multiplexed quantification of anemia biomarkers in whole blood. Sequential steps, including serum separation, target enrichment, and multiplexed readout by a gel imager, are rapidly accomplished with the flexible and highly integrated device. The microneedle array enabled efficient sampling of trace targets from ng mL -1 to pg mL -1 level. Combined with the plasmonic fluor label, the signal is improved by ≈7.6 folds compared with the flat substrate-based assay. The device is applied to simultaneously quantify hemoglobin (Hb), ferritin, folic acid (FA), and vitamin B 12 (VB 12 ), which are four anemia biomarkers distributed in different environments with different concentration ranges. Featured by the small sample volume (150 µL), short assay time (20 min), low cost (2 $), robust stability, and user-friendliness, the device is promising for the rapid and accurate diagnosis of anemia in real practice., (© 2023 Wiley-VCH GmbH.)