Microneedle Patch Research Articles

A multifunctional microneedle patch loading exosomes and magnetic nanoparticles synergistically for treating oral mucosal lesions

Oral mucosal lesions, prevalent and multifactorial disorders characterized by immune dysfunction and infection, pose significant challenges to oral functions due to the lack of effective and safe treatments. We herein introduce a multifunctional microneedle patch (MMP) that uniquely combines bone marrow mesenchymal stem cell-derived exosomes (Exos) and folic acid-magnetic nanoparticles (Fmns) within a methacrylated carboxymethyl chitosan (CMCSMA) microneedle structure. This innovative design synergistically enhances therapeutic outcomes by promoting immune regulation, angiogenesis, and epithelial repair. The MMP also features a gelatin layer for rapid pain relief via local anesthetic release and provides antimicrobial protection against opportunistic pathogens, reducing secondary infection risks. In vitro and in vivo results showed significant improvements in wound closure rates, re-epithelialization, and angiogenesis compared to control treatments. Additionally, the MMP effectively modulated immune responses, reducing inflammatory cytokine levels and promoting macrophage polarization towards a pro-healing phenotype. These findings demonstrate the efficacy and biosafety of the MMP, and highlight its potential to address critical clinical challenges in treating oral mucosal lesions, offering a multifunctional approach that integrates immune modulation, infection control, and regenerative therapy.

M2 macrophage-polarized anti-inflammatory microneedle patch for accelerating biofilm-infected diabetic wound healing via modulating the insulin pathway

Macrophages play a pivotal role in the healing of diabetic ulcers. The sustained elevation of glucose levels damages the insulin signaling pathway in macrophages, leading to dysfunctional macrophages that struggle to transition from pro-inflammatory (M1) to reparative (M2) states. Therefore, modulating macrophage inflammatory responses via the insulin pathway holds promise for diabetic ulcer treatment. Additionally, the presence of biofilm impedes drug penetration, and the resulting immunosuppressive microenvironment exacerbates the persistent infiltration of pro-inflammatory M1 macrophages. Therefore, we designed an array of dissolvable microneedle (denoted as NPF@MN) loaded with self-assembled nanoparticles that could deliver NPF nanoparticles, acid-sensitive NPF-releasing Protocatechualdehyde (PA) with hypoglycemic and insulin-like effects, regulating macrophage polarization to an anti-inflammatory M2 phenotype. Additionally, this study extensively examined the mechanism by which NPF@MN accelerates the healing of diabetic ulcers through the activation of the insulin signaling pathway. Through RNA-seq and GSEA analysis, we identified a reduction in the expression of pathway-related factors such as IR, IRS-1, IRS-2, and SHC. Our work presents an innovative therapeutic approach targeting the insulin pathway in diabetic ulcers and underscores its translational potential for clinical management.

Enhancing linezolid activity in the treatment of oral biofilms using novel chitosan microneedles with iontophoretic control

This study aimed to prepare and assess active microneedle (MN) patches based on a novel biomaterial and their effective coupled (physical and electrical) transdermal delivery of a model drug (Linezoid). Modified MN patches (e.g. fabricated from Linezoid, boronated chitosan, polyvinyl alcohol and D-sorbitol) were engineered using a vacuum micromoulding method. Physicochemical, FTIR (Fourier transform infrared), in-silico, structural and thermal analysis of prepared formulations were conducted to ascertain MN quality, composition and integrity. In-vitro mechanical tests, membrane toxicity, drug release, antibiofilm, ex-vivo mucoadhesion, insertion and in-vivo antibiofilm studies were performed to further validate viability of the coupled system. Optimized MN patch formulation (CSHP3 - comprising of 3 % w/v boronated chitosan, 3.5 % w/v PVA and 10 % w/w D-sorbitol) exhibited sharp-tipped, equi-distant and uniform-surfaced micron-scaled projections with conforming physicochemical features. FTIR analysis confirmed modification (i.e., boronation) of chitosan and compatibility as well as interaction between CSHP3 constituents. In-silico analysis indicated non-covalent interactions between all formulation constituents. Moreover, boronated chitosan-mucin glycoprotein complex showed a stronger bonding (∼1.86 times higher CScore) as compared to linezolid-mucin counterpart. Thermal analysis indicated amorphous nature of CSHP3. A ∼ 1.42 times higher tensile strength was displayed by CSHP3 as compared to control (i.e., pure chitosan, polyvinyl alcohol and D-sorbitol-based MN patch). Membrane toxicity study indicated non-toxic and physiological compatible nature of CSHP3. Within 90 min, 91.99 ± 2.3 % linezolid was released from CSHP3. During release study on agarose gel, CSHP3-iontophoresis treatment resulted in a ∼ 1.78 and ∼ 1.20 times higher methylene blue-covered area and optical density, respectively, within 60 min as compared to CSHP3 treatment alone. Staphylococcus aureus biofilms treated with CSHP3 exhibited 65 ± 4.2 % reduction in their mass. CSHP3 MN patches remained adhered to the rabbit oral mucosa for 6 ± 0.15 h. Mucosa treated with CSHP3 and CSHP3-iontophoresis combination showed a generation of pathways in the epithelium layers without any damage to the underlying lamina propria. Eradication of Staphylococcus aureus from oral mucosal wounds and complete tissue regeneration was recorded following 7-day treatment using CSHP3-iontophoresis coupled approach.

Electrochemical Aptamer-Based Biosensors for Real-Time Monitoring of Biomarkers In Vivo

There is a need for bioanalytical sensors that operate reliably for real-time monitoring of biomarkers in vivo. To address this need, we have created a hybrid sensor integrating microneedle patches with aptamer-based electrochemical sensors for monitoring glucose and lactate in vivo. We have developed a series of quality control and programmable calibration curves for measuring concentration changes in vivo. Using these methods, we have been able to monitor both lactate and glucose simultaneously in the interstitial fluid of two live animal models. Our measurements are in excellent correlation with analysis performed on blood using gold standard laboratory techniques.

The Core-Shell Microneedle with Probiotic Extracellular Vesicles for Infected Wound Healing and Microbial Homeostasis Restoration.

Wound healing is a dynamic process involving the timely transition of organized phases. However, infected wounds often experience prolonged inflammation due to microbial overload. Thus, addressing the viable treatment needs across different healing stages is a critical challenge in wound management. Herein, a novel core-shell microneedle (CSMN) patch is designed for the sequential delivery of tannic acid-magnesium (TA-Mg) complexes and extracellular vesicles from Lactobacillus druckerii (LDEVs). Upon application to infected sites, CSMN@TA-Mg/LDEV releases TA-Mg first to counteract pathogenic overload and reduce reactive oxygen species (ROS), aiding the transition to proliferative phase. Subsequently, the sustained release of LDEVs enhances the activities of keratinocytes and fibroblasts, promotes vascularization, and modulates the collagen deposition. Notably, dynamic track of microbial composition demonstrates that CSMN@TA-Mg/LDEV can both inhibit the aggressive pathogen and increase the microbial diversity at wound sites. Functional analysis further highlights the potential of CSMN@TA-Mg/LDEV in facilitating wound healing and skin barrier restoration. Moreover, it is confirmed that CSMN@TA-Mg/LDEV can accelerate wound closure and improve post-recovery skin quality in the murineinfected wound. Conclusively, this innovative CSMN patch offers a rapid and high-quality alternative treatment for infected wounds and emphasizes the significance of microbial homeostasis.

Dissolvable microneedle patch enables local delivery of immunomodulatory microparticles containing bifunctional molecules for periodontal tissue regeneration

Periodontitis is initiated by dysbiosis of the oral microbiome. Pathogenic bacteria elicit ineffective immune responses, which damage surrounding tissues and lead to chronic inflammation. Although current treatments typically aim for microbial eradication, they fail to address the significance of immune cell reactions in disease progression. Here, we searched for small molecules as drug candidates and identified a bifunctional antibiotic, azithromycin (AZM), that not only inhibits bacterial growth but also modulates immune cells to suppress inflammation. We further engineered a dissolvable microneedle patch loaded with biodegradable microparticles for local and painless delivery of AZM to the gingival tissues. Inflammatory cytokines were decreased while anti-inflammatory cytokines and M2 macrophage were increased with AZM treatments in vitro. In vivo delivery of the AZM-loaded microneedle patch demonstrated the same effects on cytokine secretion and the promotion of tissue healing and bone regeneration. In addition, microparticles containing anti-inflammatory interleukin-4 alone or in combination with separately-formulated AZM microparticles, had similar or slightly enhanced therapeutic outcomes respectively. The bimodal action of AZM obviates the necessity for separate antibacterial and immunomodulatory agents, providing a practical and streamlined approach for clinical treatment. Our findings also demonstrate the therapeutic efficacy of microparticles delivery into the soft tissues by a minimally invasive and fast-degrading microneedle patch and offer a novel therapeutic approach for the treatment of periodontitis and other diseases through immunomodulation.Graphical

A minimally invasive sensing system based on hydrogel microneedle patches and Au/Cu2O nanospheres modified screen-printed carbon electrode for glucose monitoring in interstitial skin fluid

Glucose monitoring in interstitial skin fluid (ISF) has become a novel approach for diabetes management. In this paper, a minimally invasive sensing system consisted of methacrylated hyaluronic acid (MeHA) based microneedle patches and Au/Cu2O nanospheres modified screen-printed carbon electrode (SPCE) was designed for glucose monitoring in the ISF of living mice. The highly swellable and biocompatible MeHA microneedle patches can effectively extract ISF from the skin, barely cause pain to the living mice. The glucose level in the extracted ISF was detected via an enzyme-free electrochemical sensor using the Au/Cu2O nanospheres as the electrocatalyst. The doping of Au into Cu2O resulted in a highly conductive and active electrocatalyst for glucose oxidation, which improved the sensing performance of glucose sensor. A wide linear range (0.02 – 6 mM), low detection limit (0.018 mM), and high sensitivity (110.38 μA mM−1 cm−2) were obtained under the optimized condition. The obtained results exhibited a comparable trend to those obtained from commercial glucometers. We have combined successfully MeHA patches for ISF extraction with enzyme-free electrochemical glucose sensor. Therefore, this novel sensing system holds great potential for diabetes management in a minimally invasive manner.

Sustained release microneedle patch for pronounced systemic delivery of doxazosin mesylate

Introduction: Microneedle patch is one of the fascinating drug delivery approaches that offers low invasiveness and a painless physical application to enhance the delivery of micro and macro-molecules into the skin. Methods: Variable contents of chitosan and polyvinyl alcohol were used for the development of doxazosin mesylate containing sustained release microneedle patches via solvent casting technique. The prepared patches were evaluated for microscopic evaluation, mechanical strength, drug loading (%) and Fourier transform infrared spectroscopy (FTIR) etc. The skin penetration study was performed by using pig ear skin and results were captured through confocal microscopy. Ex-vivo release study and pharmacokinetic evaluation were also performed. Results: Sharp needle tips with a height of 600µm and a base of 200µm were confirmed through microscopic examination. Optimized formulation (SRF-6) exhibited loading of 92.11% doxazosin mesylate with appreciable strength up to 1.94N force. Ex-vivo release studies revealed 87.24% release within 48 hours. Moreover, the pharmacokinetic parameters in case of optimized patch formulation (SRF-6) were markedly improved i.e. MRT (19.46 h), AUC (57.12 μg.h /mL), Cmax (2.16 µg /mL), tmax (10.10 h) and t1/2 (6.32 h) as compared to commercially available tablet. Biocompatibility of the developed patches was validated from skin irritation studies. Conclusion: Results confirmed the successful fabrication of microneedle patch having sufficient strength and effective penetration ability into the skin to ensure controlled release of incorporated drug for the intended duration. It can be employed as an efficient carrier system for other therapeutics those are prone to bioavailability issues due to first pass effect after their oral administration.

Glucose detection: In-situ colorimetric analysis with double-layer hydrogel microneedle patch based on polyvinyl alcohol and carboxymethyl chitosan

Skin interstitial fluid (ISF) has emerged as a significant reservoir of biomarkers for disease diagnosis and prevention. Microneedle (MN) patches are regarded as an optimal platform for ISF extraction from the skin due to their non-invasive nature. However, challenges such as prolonged sampling durations and complex detection procedures impede timely metabolic analysis. In this investigation, we amalgamated MN technology with immobilized enzyme technology to fabricate a dual-layer MN patch integrating sampling and detection functionalities, thereby enabling in-situ colorimetric detection of hyperglycemia. The tip layer of the patch, comprising polyvinyl alcohol/carboxymethyl chitosan (PVA/CMCS) MN, was synthesized utilizing a chemical crosslinking approach for the first time, with glucose oxidase (GOx) being incorporated. The hydrophilicity of CMCS expedited the extraction process, facilitating the retrieval of approximately 10 mg of ISF within 10 min. The backing layer consisted of an immobilized polyvinyl alcohol-chitosan-horseradish peroxidase (PVA-CS-HRP) hydrogel film loaded with 3,3′, 5,5′-tetramethylbenzidine (TMB). Incorporating macromolecular polymer PVA and CS for HRP immobilization addressed the issue of poor stability associated with traditional natural enzymes, thereby enhancing the sensitivity of the reaction system. The in-situ colorimetric sensor facilitated minimally invasive ISF extraction and swift conversion of glucose levels into detectable color changes.

Micro/nano system-mediated local treatment in conjunction with immune checkpoint inhibitor against advanced-Stage malignant melanoma

Tumor relapse and metastasis become a big challenge in treating malignant melanoma because conventional therapeutic options often fail to eradicate the tumor residue after surgical resection, posing huge threat to human health. Herein, a feasible strategy is developed for fighting crafty melanoma pre- and postsurgery. Specifically, nitric oxide (NO)-carried micelles (NOM) are designed by conjugating S-nitrosoglutathione (GSNO) with poly(2-ethyl-2-oxazoline)-b-poly(D, L-lactide) (PEOz-b-PLA) to form amphipathic polymer, which can self-assemble into pH-sensitive micelle to encapsulate chemotherapeutic drug paclitaxel (PTX). By further loading PTX@NOM into the needle tips of dissolvable microneedle (MN) patch, a local synergistic strategy is achieved for combating melanoma via easy insertion. Meanwhile, due to the immunomodulatory ability of NO by inducing the immunogenic cell death (ICD) of tumor cells and polarizing M2-like tumor-associated macrophages (TAMs) into antitumoral M1-like type, the “cold” immune microenvironment of melanoma is effectively remodeled. When combining with aPD-L1-based immune checkpoint blockade therapy, the treatment outcome of aPD-L1 is dramatically boosted, which not only suppresses primary tumor growth, but also inhibits the notorious post-operative melanoma recurrence and metastasis. Overall, this local strategy mediated by nanoparticle-loaded MN patch expands the therapeutic regimen for melanoma treatment in clinic.

“All-in-one” metal polyphenol network nanocapsules integrated microneedle patches for lipophagy fueled ferroptosis-mediated multimodal therapy

Ferroptosis-mediated multimodal therapy has emerged as a promising strategy for tumor elimination, with lipid peroxide (LPO) playing a pivotal role. However, the therapeutic efficiency is limited due to insufficient intracellular levels of free fatty acids (FFA), which severely hinder the production of LPO. To address this limitation, we proposed a lipophagy strategy aimed at degrading lipid droplets (LDs) to release FFA, serving as the essential “fuel” for LPO production. In this study, the lipophagy inducer epigallocatechin gallate (EGCG) was self-assembled with reactive oxygen species (ROS)-producer phenethyl isothiocyanate (PEITC) mediated by Fe2+ to form EFP nanocapsules, which were further integrated into microneedle patches to form a “all-in-one” EFP@MNs. The metal-polyphenol network structure of EFP endow it with photothermal therapy capacity. Upon insertion into tumors, the released EFP nanocapsules were demonstrated to induce lipophagy through metabolic disturbance, thereby promoting LPO production and facilitating ferroptosis. When combined with photothermal therapy, this approach significantly remolded the tumor immune microenvironment by driving tumor-associated macrophages toward M1 phenotype and enhancing dendritic cell maturation. Encouragingly, in conjunction with αPD-L1 treatment, the proposed EFP@MNs exhibited remarkable efficacy in tumor ablation. Our study presents a versatile framework for utilizing microneedle patches to power ferroptosis-mediated multimodal therapy.

Potential of Pullulan-Based Polymeric Nanoparticles for Improving Drug Physicochemical Properties and Effectiveness.

This scientific review aims to comprehensively discuss and summarize recent advancements in pullulan-based polymeric nanoparticles, focusing on their formulation, characterization, evaluation, and efficacy. A search on Scopus, PubMed, and Google Scholar, using "Pullulan and Nanoparticle" as keywords, identified relevant articles in recent years. The literature search highlighted a diverse range of studies on the pullulan-based polymeric nanoparticles, including the success of high-selectivity hybrid pullulan-based nanoparticles for efficient boron delivery in colon cancer as the active targeting nanoparticle, the specific and high-efficiency release profile of the development of hyalgan-coated pullulan-based nanoparticles, and the design of multifunctional microneedle patches that incorporated pullulan-collagen-based nanoparticle-loaded antimicrobials to accelerate wound healing. These studies collectively underscore the versatility and transformative potential of pullulan-based polymeric nanoparticles in addressing biomedical challenges. Pullulan-based polymeric nanoparticles are promising candidates for innovative drug delivery systems, with the potential to overcome the limitations associated with traditional delivery methods.

Plant-Derived Chinese Herbal Hydrogel Microneedle Patches for Wound Healing.

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.

Designing Polyelectrolyte Microneedles Based on Borylated Poly(β-aminoester) Polymers To Enhance Transdermal pH-Controlled Delivery of Nucleic Acids.

The use of transdermal delivery for nucleic acid administration is an interesting approach to overcoming limitations of systemic administration routes, such as first-pass effects, the painful needle injection, or their poor biodistribution. Thus, the use of a microneedle-based patch could represent a turning point for nucleic acid delivery, thanks to the possibility of self-administration of the actives in a painless and easy procedure. However, the design of transdermal systems with a higher degree of precision release is a clear need that has not been fully resolved. Committed to tackling this challenge, we present here a microneedle patch that involves a smart delivery system supported by the well-established ability of boronic acid to interact with carbohydrates in a pH-dependent manner. This system builds up a multilayer structure over a solid microneedle platform whose surface has been modified to immobilize glucosamine units that are able to interact with an oligopeptide-end terminated poly(β-aminoester) that presents a 4-carboxy-3-fluorophenylboronic acid (Bor-pBAE). Thus, sequential layers of the Bor-pBAE and plasmid DNA have been assembled, thanks to the ability of the polymer to interact with the nucleic acid at a basic pH and then gradually release the plasmid under two different conditions of pH (the physiological pH = 7.4 and the acidic pH = 5.1). We set up the design and implementation of this first proof of concept while demonstrating microneedles' safety and functionality. Additionally, we have shown the efficacy of the construct to express the encoded genes in model cell lines. In conclusion, we have established the basis to confirm that this generation of borylated poly(β-aminoesters) holds great promise as a transdermal local nucleic acid delivery system.

Self‐Nanoformulating Poly(2‐oxazoline) and Poly(2‐oxazine) Copolymers Based Amorphous Solid Dispersions as Microneedle Patch: A Formulation Study

AbstractA pioneering approach in the domain of transdermal drug delivery systems (TDDS) is introduced by using microneedles (MNs) fabricated from an amorphous solid dispersion comprising only a model drug and an amphiphilic block copolymer to form a drug nanoformulation upon MN dissolution. To maximize drug loading and ensure consistent release, a minimalist formulation that achieves 40 wt% drug loading, which is a significant improvement over existing methods, is developed. Using scanning electron microscopy, the morphology of MNs is examined across a spectrum of drug loading ratios, demonstrating the consistency in structure and integrity. Mechanical testing confirms the MNs' proficiency in effective skin penetration. A comparative study on the formation of polymeric micelles underscores the innovative concept of a “nano‐in‐micro drug delivery system”. The results demonstrate that MNs manufactured from an amorphous solid dispersion of drug and amphiphilic block copolymer with ultra‐high loading enhance the availability and release dynamics of hydrophobic drugs, positioning them as a tool for enhancing TDDS. This study sets a new benchmark in the utilization of polymer‐drug nanoformulations for transdermal applications and underscores the capacity for high drug loading and the creation of adaptable drug delivery mechanisms for the studied amphiphilic block copolymer.

The Relationship between Immunogenicity and Reactogenicity of Seasonal Influenza Vaccine Using Different Delivery Methods.

Vaccine immunogenicity and reactogenicity depend on recipient and vaccine characteristics. We hypothesized that healthy adults reporting higher reactogenicity from seasonal inactivated influenza vaccine (IIV) developed higher antibody titers compared with those reporting lower reactogenicity. We performed a secondary analysis of a randomized phase 1 trial of a trivalent IIV delivered by microneedle patch (MNP) or intramuscular (IM) injection. We created composite reactogenicity scores as exposure variables and used hemagglutination inhibition (HAI) titers as outcome variables. We used mixed-model analysis of variance to estimate geometric mean titers (GMTs) and titer fold change and modified Poisson generalized estimating equations to estimate risk ratios of seroprotection and seroconversion. Estimates of H3N2 GMTs were associated with the Systemic and Local scores among the IM group. Within the IM group, those with high reaction scores had lower baseline H3N2 GMTs and twice the titer fold change by day 28. Those with high Local scores had a greater probability of seroconversion. These results suggest that heightened reactogenicity to IM IIV is related to low baseline humoral immunity to an included antigen. Participants with greater reactogenicity developed greater titer fold change after 4 weeks, although the response magnitude was similar or lower compared with low-reactogenicity participants.

Stick-and-sensing microneedle patch for personalized nutrition management

The focus of the next-generation healthcare system has moved forward from single disease detection to comprehensive health interpretation, namely, from disease diagnosis to prophylaxis via the early management of sub-health status. Among the technologies, microneedles have emerged as an efficient and powerful tool to realize painless and real-time sensing in the interstitial fluid (ISF), offering promising solutions for dynamic and direct reflection of nutritional profiles. Herein, we present a film-like, multifunctional microneedle patch, that is composed of three laser-induced graphene (LIG) based electrodes for minimally invasive and timely detection of glucose and vitamin C in the ISF. The microneedle patch is simply fabricated with a thickness of ∼0.25 mm polyimide (PI) film by a commercial laser platform, where laser-engraving is operated to form graphene electrodes, and laser-cutting accounts for the needle-tip shaping. Such fast, low-cost, and scalable manufactured microneedle patches showed excellent performance for electrochemical sensing and therefore allowed reliable on-the-tip monitoring of changes in glucose and vitamin C levels. Long-term studies in vivo and demonstrations in planta indicated the great promise of our microneedle patch to revolutionize dietary guidelines based on individualized status for effective nutrition management.

Dual-Barb Microneedle with JAK/STAT Inhibitor-Loaded Nanovesicles Encapsulation for Tendinopathy.

Tendon stem/progenitor cells (TSPCs) are crucial for tendon repair, regeneration, and homeostasis. Dysfunction of TSPCs, due to aberrant activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, contributes to tendinopathy. Unfortunately, the effectiveness of conventional subcutaneous injection targeting at suppressing JAK/STAT signaling pathway is limited due to the passive diffusion of drugs away from the injury site. Herein, a novel poly-gamma-glutamic acid (γ-PGA) dual-barb microneedle (MN) path loaded with TSPCs-derived nanovesicles (NVs) containing JAK/STAT inhibitor WP1066 (MN-WP1066-NVs) for tendinopathy treatment is designed. The dual-barb design of the MN ensures firm adhesion to the skin, allowing for sustained and prolonged release of WP1066-NVs, facilitating enhanced TSPCs self-renewal, migration, and stemness in tendinopathy. In vitro and in vivo experiments demonstrate that the degradation of γ-PGA patch tips facilitates the gradual release of WP1066-NVs at the lesion site. This release alleviates inflammation, suppresses extracellular matrix degradation, and restores normal tendon histological structure by inhibiting the JAK/STAT pathway. These findings suggest that the multifunctional dual-barb MN patch offers a novel and effective therapeutic strategy for tendinopathy treatment.

Nanoparticle-Patch System for Localized, Effective, and Sustained miRNA Administration into Infarcted Myocardium to Alleviate Myocardial Ischemia-Reperfusion Injury.

Timely blood reperfusion after myocardial infarction (MI) paradoxically triggers ischemia-reperfusion injury (I/RI), which currently has not been conquered by clinical treatments. Among innovative repair strategies for myocardial I/RI, microRNAs (miRNAs) are expected as genetic tools to rescue damaged myocardium. Our previous study identified that miR-30d can provide protection against myocardial apoptosis and fibrosis to alleviate myocardial injury. Although common methods such as liposomes and viral vectors have been used for miRNA transfection, their therapeutic efficiencies have struggled with inefficient in vivo delivery, susceptible inactivation, and immunogenicity. Here, we establish a nanoparticle-patch system for miR-30d delivery in a murine myocardial I/RI model, which contains ZIF-8 nanoparticles and a conductive microneedle patch. Loaded with miR-30d, ZIF-8 nanoparticles leveraging the proton sponge effect enable miR-30d to escape the endocytic pathway, thus avoiding premature degradation in lysosomes. Meanwhile, the conductive microneedle patch offers a distinct advantage by intramyocardial administration for localized, effective, and sustained miR-30d delivery, and it simultaneously releases Au nanoparticles to reconstruct electrical impulses within the infarcted myocardium. Consequently, the nanoparticle-patch system supports the consistent and robust expression of miR-30d in cardiomyocytes. Results from echocardiography and electrocardiogram (ECG) revealed improved heart functions and standard ECG wave patterns in myocardial I/RI mice after implantation of a nanoparticle-patch system for 3 and 6 weeks. In summary, our work incorporated conductive microneedle patch and miR-30d nanodelivery systems to synergistically transcend the limitations of common RNA transfection methods, thus mitigating myocardial I/RI.

Gallium Nanostructure‐Based Microneedle Patch for Multidrug‐Resistant Bacterial Wound Healing: Enhanced Metal Release and NIR Photothermal Effect

AbstractBacterial infections, especially caused by multidrug‐resistant bacteria, pose a big challenge to the healthcare system. As a group of historic agents, metals with broad‐spectrum antibacterial activity are regarded as promising alternatives to tackle antibiotic resistance. Among them, gallium ions have presented encouraging antibacterial effects in research and preclinic studies. However, utilization of gallium ions has difficulty in achieving high targeting and long‐term effectiveness. With the renaissance of liquid metal, here, a novel and facile antibacterial gallium nanostructure is proposed in which polydopamine‐modified gallium nanocore serves as an ion reservoir for enhanced metal ion release and the surface also permits secondary reaction, allowing for in situ formation of Ag nanoparticles to improve the antibacterial property, ROS generation, and photothermal performance. Notably, ≈100% bacterial killing efficacy can be achieved when combined with NIR laser irradiation. The in vivo treatment results of methicillin‐resistant Staphylococcus aureus (MRSA)‐infected mice demonstrate that the microneedle patch loaded with nanoparticles exhibits outstanding bacterial elimination and inflammation alleviation, and promotes angiogenesis and collagen deposition, further accelerating wound healing. This gallium‐based nanostructure offers an effective nanoplatform for antibacterial treatments and combinatory strategies, which holds significant promise for refractory multidrug‐resistant bacteria and related infections.