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ADVANCED FUNCTIONAL MATERIALS · 2025 · IF 19

Microenvironment-Regulated Dual-Layer Microneedle Patch for Promoting Periodontal Soft and Hard Tissue Regeneration in Diabetic Periodontitis

Yaning Qu,Huajing Zeng,Lei Wang,Zhenlin Ge,Bin Liu,Zengjie Fan

Chronic periodontitis in individuals with diabetes can exacerbate the destruction of local periodontal soft tissues and accelerate the resorption of hard tissue. Currently, effective strategies to simultaneously restore both soft and hard periodontal tissues remain insufficient. To address this challenge, a multifunctional dual-layer microneedles (d-MNs) design is proposed to regenerate both periodontal soft and hard tissues in diabetic patients. The d-MNs substrate is composed of gelatin methacryloyl (GelMA) infused with nano-hydroxyapatite (nHA), which facilitates the differentiation of osteogenic cells into osteoblasts, thereby promoting alveolar bone regeneration. The tips of the d-MNs, on the other hand, are primarily made of hyaluronic acid (HA) combined with a magnesium-based metal-organic framework (Mg-MOF) loaded with glucose oxidase (GOX). This composition creates a hypoglycemic, angiogenic, and anti-inflammatory microenvironment, which supports soft tissue repair. When implanted at the site of periodontitis, the synergistic interaction between the d-MNs substrate and tips effectively promotes the regeneration of both soft and hard tissues, as demonstrated in diabetic rat models of periodontitis. These innovative d-MNs have the potential to revolutionize traditional approaches to treating diabetic periodontitis and can see broad application in dental clinics.

CAS / MDL: 1306-06-5 1898-66-4
研究领域: 口腔医学 · 生物材料学 · 再生医学
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LANGMUIR · 2025 · IF 3.9

Bilayer Microneedle Patch Loaded with Keratin-Based Hydrogen Sulfide Donor and Ciprofloxacin for Diabetic Wound Healing

Fengni Liu,Haiping Hu,Yu Sun,Zhaoyan Ge,Jian Shen,Jiang Yuan

Persistent overoxidation, inflammation, and bacterial infection impede diabetic wound healing. As the third biological gasotransmitter, hydrogen sulfide (H2S) can modulate inflammation, mitigate oxidative stress, and facilitate angiogenesis, potentially promoting diabetic wound healing. In this study, bilayer microneedle patches (MNs) were prepared through a two-step mold-casting process using blends of poly(vinyl alcohol) and poly(vinylpyrrolidone) as substrates. The tip layer was loaded with a keratin-based hydrogen sulfide donor (KAT) and ciprofloxacin hydrochloride (CIP), while the backing layer was integrated with glutathione and CIP. The patches exhibited a well-arranged microarray and enough mechanical properties to penetrate the skin. The patches demonstrated the self-catalytic generation of H2S and the delivery of CIP. Additionally, the patches exhibited excellent antioxidant and antibacterial properties. More importantly, MNs can polarize macrophages to anti-inflammatory phenotypes (M2), enhance the proliferation and migration of L929 cells, and promote HUVEC angiogenesis. The wound healing in diabetic rat models confirmed that the MN patches reduced the inflammatory response, accelerated collagen deposition, and promoted neovascularization, thereby accelerating diabetic wound healing. Overall, the bilayer patches demonstrated outstanding potential for wound dressing applications.

CAS / MDL: 102879-44-7
研究领域: 生物医学工程 · 药剂学 · 伤口愈合 · 纳米技术 · 生物化学
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Journal of Materials Chemistry B · 2025 · IF 5.7

Spray-drying-engineered CS/HA-bilayer microneedles enable sequential drug release for wound healing

Haowen Zhong,Zongyou Chen,Jiahao Huang,Xiao Yu,Chengyong Wang,Yue Zheng,Mengran Peng,Zhishan Yuan

High incidence and mortality rates of chronic wounds place a heavy burden on global healthcare systems. Achieving phased delivery of antimicrobial and regenerative drugs is crucial for promoting chronic wound healing. Herein, a microneedle (MN) patch with a biphasic release system was developed using a combination of solvent casting and spraying methods. Additionally, a copper/PDMS mold was introduced to address the issue of deformation in the chitosan material during drying on polydimethylsiloxane (PDMS). The MNs have a bilayer structure, with a hyaluronic acid (HA) coating loaded with doxycycline (DOX) for antibacterial action and a chitosan (CS) core loaded with vascular endothelial growth factor (VEGF) for promoting cell migration and proliferation. Notably, in vitro drug release studies showed that the coating drug was released by 98.8% within 10 hours, while the release of the core drug could be sustained for up to 70 hours. In vivo studies showed that chronic wounds on C57 mice treated with CS/HA-bilayer MNs achieved nearly complete healing by day 9. These wounds exhibited reduced inflammatory cell infiltration, increased epithelial tissue regeneration, and enhanced collagen deposition. This work integrates the staged management of bacterial infection and angiogenesis and offers promising prospects for enhancing chronic wound healing.

CAS / MDL: 81-88-9 7558-80-7
研究领域: 生物医学工程 · 药剂学 · 组织工程
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Biomaterials Advances · 2024 · IF 5.5

Reactive oxide species and ultrasound dual-responsive bilayer microneedle array for in-situ sequential therapy of acute myocardial infarction

Qingqing Wang,Shuangyuan Cao,Teng Zhang,Fanzhen Lv,Mingfei Zhai,Danmeng Bai,Mengzhen Zhao,Haoxin Cheng,Xiaolei Wang

Acute myocardial infarction (AMI) resulting from coronary artery occlusion stands as the predominant cause of cardiovascular disability and mortality worldwide. An all-encompassing treatment strategy targeting pathological processes of oxidative stress, inflammation, proliferation and fibrotic remodeling post-AMI is anticipated to enhance therapeutic outcomes. Herein, an up-down-structured bilayer microneedle (Ce-CLMs-BMN) with reactive oxygen species (ROS) and ultrasound (US) dual-responsiveness is proposed for AMI in-situ sequential therapy. The upper-layer microneedle is formulated by crosslinking ROS-sensitive linker with polyvinyl alcohol loaded with cerium dioxide nanoparticles (CeNPs) featuring versatile enzyme-mimetic activities. During AMI acute phase, prompted by ischemia-induced microenvironmental redox imbalance, this layer swiftly releases CeNPs, which aid in eliminating excessive ROS and catalyzing oxygen gas (O 2 ) production through multiple enzymatic pathways, thereby alleviating oxidative stress-induced damage and modulating inflammation. In AMI chronic repair phase, micro-nano reactors (CLMs) situated in the lower-layer microneedle undergo cascade reactions with the assistance of US irradiation to generate nitric oxide (NO). As a bioactive molecule with pro-angiogenic and anti-fibrotic effects, NO expedites cardiac repair while attenuating adverse remodeling. Additionally, its antiplatelet-aggregating properties contribute to thromboprophylaxis. In-vitro and in-vivo results substantiate the efficacy of this integrated healing approach in AMI management, showcasing promising prospects for advancing infarcted heart repair.

研究领域: 心血管疾病 · 纳米技术 · 药物递送系统 · 生物医学工程 · 分子生物学
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Bioactive Materials · 2024 · IF 18

Dual-layer microneedles with NO/O2 releasing for diabetic wound healing via neurogenesis, angiogenesis, and immune modulation

Changjiang Liu,Kun Liu,Dong Zhang,Yuting Liu,Yifeng Yu,Haifei Kang,Xianzhen Dong,Honglian Dai,Aixi Yu

Diabetic wounds present multiple functional impairments, including neurovascular dysregulation, oxidative imbalance, and immune dysfunction, making wound healing particularly challenging, while traditional therapeutical strategies fail to address these complex issues effectively. Herein, we propose a strategy utilizing dual-layer microneedles to deliver therapeutic gases by modulating neurovascular coupling and immune functions for diabetic wound treatment. The microneedle can respond to reactive oxygen species (ROS) in the diabetic microenvironment and subsequently generate oxygen (O 2 ) and nitric oxide (NO). These gases comprehensively promote neuro-vascular regeneration, reduce oxidative stress levels, and attenuate inflammation. In vivo studies demonstrate that the microneedle can accelerate diabetic wound healing by modulating neurovascular regeneration and inflammatory processes. Transcriptomic analyses further validate the involvement of related advantageous signaling pathways. The potential mechanism involves the activation of the PI3K-AKT-mTOR pathway to facilitate autophagy, ultimately accelerating the healing process. Thus, our multifunctional dual-layer microneedles provide an effective strategy for treating diabetic wounds.

研究领域: 生物医学工程 · 药理学 · 伤口愈合 · 糖尿病研究 · 神经科学 · 免疫学
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