INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2025
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IF 5.2
Lujie Zhang,Qinghua Song,Peijing Yang,Zhanqiang Liu
Microneedle (MN) technology is a promising minimally invasive tool for interstitial skin fluid (ISF) extraction. Hydrogel MN patches enable efficient ISF extraction. However, the traditional polydimethylsiloxane (PDMS) photopolymerization method has limitations in morphology control, accuracy, and susceptibility to process parameter interference, affecting MN strength and functional consistency. To address these challenges, we propose a composite hydrogel MN patch based on Digital Light Processing (DLP) 3D bioprinting of hyaluronic acid methacryloyl (HAMA)/gelatin methacryloyl (GelMA) for high-efficiency ISF transdermal extraction. The structure and performance of the MNs were improved by optimizing the bio-ink ratio and printing parameters. Adjusting the ratio of GelMA and HAMA improved the cross-linking structure, optimizing the mechanical properties and swelling performance of the composite hydrogel. Optimizing the light intensity and exposure time ensured consistent MN morphology, resulting in well-defined and evenly distributed needle tips. Controlled UV exposure avoided defects such as uneven cross-linking or brittleness. The results showed that when the HAMA-to-GelMA ratio was 8:2, the light intensity was 9 mW/cm 2 , and the exposure time was 6 s, the MN patches demonstrated excellent microstructures and mechanical properties, with each MN enduring over 1.28 N and achieving a swelling rate above 1200 %. In vitro experiments verified effective penetration and ISF extraction, obtaining 8.5 mg of PBS in 1 min and successfully quantifying glucose concentration. In summary, this study establishes a robust MN patch with superior swelling performance and enhanced ISF extraction efficiency and provides a promising platform for minimally invasive diagnosis and real-time health monitoring.
研究领域:
生物医学工程
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材料科学
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药学
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DOI
PubMed
高影响因子
Journal of the Mechanical Behavior of Biomedical Materials
·
2025
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IF 3.5
Bincan Deng,Sibai Chen,Fernando López Lasaosa,Xuan Xue,Chen Xuan,Hongli Mao,Yuwen Cui,Zhongwei Gu,Manuel Doblare
- Rheological properties are pivotal in determining the printability of biomaterials, directly impacting the success of 3D bioprinted constructs. Understanding the intricate relationship between biomaterial formulations, rheological behavior and printability can facilitate the advancement and rapid development of biomaterials. Herein, we critically measured the rheological properties of hyaluronic acid methacrylate (HAMA)/gelatin methacrylate (GelMA) hybrid hydrogels with varied formulations and generated a dataset to train a machine learning (ML) model. By utilizing four well-known algorithms, we developed the ML model for the viscosity and shear stress of HAMA/GelMA hydrogel mixtures. To improve model interpretability, we further created a multilayer perceptron framed model, known as HydroThermoMLP, by incorporating the Redlich-Kister polynomial as the thermodynamic representation of viscosity of mixtures. To accomplish the MLP learning on limited data, the shared loss function was formulated on the basis of the R-K presentation to guide the joint training process. The established HydroThermoMLP model, while maintaining the same accuracy as Random Forest, produces outputs that adhere to thermodynamic constraints and instill confidence in generalization applications with a simple algorithm informed by the R-K polynomial. It presents a robust predictive ML tool to forecast the viscosity of hybrid hydrogels and direct the design of biomaterials while appropriately abiding by thermodynamic constraints as essential guidelines.
研究领域:
生物材料学
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医学工程
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人工智能应用
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-29
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IF 10.6
Yu Xiao-Jun,Zhao Yuan-Ting,Abudouaini Haimiti,Zou Peng,Li Tian-Qi,Bai Xiao-Fan,Wang Shan-Xi,Guan Jian-Bin,Li Meng-wei,Wang Xiao-dong,Wang Ying-guang,Hao Ding-Jun
Methods Single-cell transcriptomics and high-throughput transcriptomics were used to screen factors significantly correlated with intervertebral disc degeneration (IDD). Expression changes of CFIm25 were determined via RT-qPCR and Western blot. NP cells were isolated from mouse intervertebral discs and induced to degrade with TNF-α and IL-1β. CFIm25 was knocked out using CRISPR-Cas9, and CFIm25 knockout and overexpressing nucleus pulposus (NP) cell lines were generated through lentiviral transfection. Proteoglycan expression, protein expression, inflammatory factor expression, cell viability, proliferation, migration, gene expression, and protein expression were analyzed using various assays (alcian blue staining, immunofluorescence, ELISA, CCK-8, EDU labeling, transwell migration, scratch assay, RT-qPCR, Western blot). The GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA was designed, and its effects on NP regeneration were assessed through in vitro and mouse model experiments. The progression of IDD in mice was evaluated using X-ray, H&E staining, and Safranin O-Fast Green staining. Immunohistochemistry was performed to determine protein expression in NP tissue. Proteomic analysis combined with in vitro and in vivo experiments was conducted to elucidate the mechanisms of hydrogel action. Results CFIm25 was upregulated in IDD NP tissue and significantly correlated with disease progression. Inhibition of CFIm25 improved NP cell degeneration, enhanced cell proliferation, and migration. The hydrogel effectively knocked down CFIm25 expression, improved NP cell degeneration, promoted cell proliferation and migration, and mitigated IDD progression in a mouse model. The hydrogel inhibited inflammatory factor expression (IL-6, iNOS, IL-1β, TNF-α) by targeting the p38/NF-κB signaling pathway, increased collagen COLII and proteoglycan Aggrecan expression, and suppressed NP degeneration-related factors (COX-2, MMP-3). Conclusion The study highlighted the crucial role of CFIm25 in IDD and introduced a promising therapeutic strategy using a porous spherical GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA. This innovative approach offers new possibilities for treating degenerated intervertebral discs. Graphical Abstract Molecular mechanism of GCA targeting CFIm25 in NP cells to promote regeneration of degenerated intervertebral disc NP
研究领域:
生物医学工程
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再生医学
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组织工程
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分子生物学
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细胞生物学
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骨科
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DOI
PubMed
高影响因子
ACS Omega
·
2025
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IF 4.3
Tai Zhou,Xue Liu,Zhimin Wu,Riley Lyu,Caizhi Peng,Hongyi Zhang,Yajing Xia
Background: Skin wound healing is a common clinical challenge, facing multiple obstacles including delayed healing, local hypoxia, and bacterial infection, which may lead to prolonged nonhealing or wound infection. Traditional therapeutic strategies mostly intervene in single factors, making it difficult to achieve synergistic effects. Therefore, developing an innovative approach to simultaneously address multiple issues is of great significance. Objective: This study aims to develop a multifunctional hydrogel patch (Cu–Fe3O4-loaded HAMA, CFH) by integrating three core functions of promoting healing, supplying oxygen, and antibacterial activity, achieving a “one-for-three” therapeutic effect to provide a more comprehensive solution for wound repair. Methods: Cu–Fe3O4 nanoclusters (NCs) were synthesized via a hot solvent method, and CFH hydrogel patches were constructed using molds. In vitro experiments were performed to verify their biosafety, antibacterial properties, and nanozyme activity. A mouse full-thickness skin defect model was established to validate the wound-healing effect of CFH hydrogel patches in vivo. Results: Cu–Fe3O4 NCs were successfully synthesized, exhibiting good biocompatibility and significantly promoting the proliferation and migration of human skin fibroblasts (HSFs). Meanwhile, the material showed excellent nanozyme activity, effectively catalyzing the decomposition of hydrogen peroxide and glutathione to remarkably improve local oxygen supply in wounds. Antibacterial experiments confirmed significant inhibitory effects against MRSA and Escherichia coli. In vivo experiments further demonstrated that CFH hydrogel patches adhered well to wounds, enabling rapid, efficient, and aseptic wound healing within 14 days. Conclusions: This study successfully developed a multifunctional CFH hydrogel patch based on Cu–Fe3O4 NCs, integrating three functions of promoting cell proliferation, improving oxygen supply, and broad-spectrum antibacterial activity. It provides a safe and efficient novel therapeutic strategy for clinical wound repair, holding important clinical application value.
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产品关联
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2026
·
IF 7.8
Ying Hu,Yu Wu,Yuansen Luo,Xiangkai Kong,Delong Zhu,Kunrui Wang,Xiang Lan,Lei Zhu,Tao Xu,Kun Wang
Diabetic wound healing impairment poses significant clinical challenges due to infection risks, poor angiogenesis, and chronic inflammation, often leading to amputation or death. Recently, mesenchymal stem cell-derived exosomes (Exos) exhibit potential in enhancing angiogenesis and suppressing inflammation, yet clinical application is limited by short half-life, low bioavailability, and high costs. Three-dimensional (3D) culture technology improves exosome yield and therapeutic efficacy, demonstrating superior performance in tissue regeneration. Concurrently, microneedle (MN) systems enable efficient transdermal drug delivery with minimal invasiveness. This study integrates 3d-Exo with Mupirocin into a hyaluronic acid methacrylate (HAMA)-based MN patch (3d-Exo MN) to enhance diabetic wound healing. The HAMA matrix ensures exosome stability and controlled release, while Mupirocin targets infection. In vitro and in vivo evaluations reveal that 3d-Exo MN significantly promotes cell proliferation, migration, and neovascularization, addressing key limitations of conventional therapies. By synergizing 3d-Exo advantages with MN-mediated delivery, this innovative platform offers a targeted, biocompatible strategy for diabetic wound management, bridging gaps in current treatment paradigms through enhanced drug efficacy and localized action.
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DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2025
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IF 5.6
Jiashuai Yan,Di Wu,Biwen Zhu,Xiaoqi Guan,Xue Zhang,Yibing Guo,Yuhua Lu
As a highly aggressive solid tumor, pancreatic ductal adenocarcinoma (PDAC) is featured by a conspicuous tumor microenvironment (TME) with abundant extracellular matrix (ECM) deposition, such as collagen and hyaluronic acid (HA). Accompanying with the pathological process, the dense matrix caused stiffen microenvironment, which leads to poor chemotherapy. Therefore, understanding the potential mechanism of mechanical microenvironment on PDAC chemoresistance is of great significance. To this end, 3D printed methacrylated gelatin (GelMA) and hyaluronic acid methacryloyly (HAMA) hydrogel model was fabricated to resemble the mechanical microenvironment of PDAC. The results presented that the PDAC cell lines (MIA-PaCa2 and PANC-1) embedded in the hydrogel were distinctively less sensitive to gemcitabine compared to tissue culture plate (TCP) group. Interestingly, immunofluorescence staining and qRT-PCR assay demonstrated that the NRF2 level was elevated, which further upregulated the downstream effectors, such as SLC7A11 and GPX4. Meanwhile, the GSH concentration and GPX4 activity of hydrogel group were increased, while the lipid peroxidation level was reduced, which indicated that the matrix stiffness microenvironment mediated ferroptosis phenotype. Furthermore, RNA interference experiment elaborated that shNRF2 group showcased significantly enhanced sensitivity to gemcitabine, which demonstrated that the biomimetic microenvironment modulated chemoresistance through ferroptosis. All in all, the 3D printed model may serve as a new platform for illustrating the underlying mechanism of the TME induced chemoresistance, and also proposed a novel therapeutic strategy for PDAC through NRF2 inhibition, which effectively promotes ferroptosis to overcome chemoresistance.
研究领域:
肿瘤学
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细胞生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2026
·
IF 3.1
Bincan Deng,Dingding Chen,Fernando López Lasaosa,Caimiao Zheng,Yiyan He,Chen Xuan,Yuwen Cui
Reliable viscosity prediction of methacrylated hyaluronic acid (HAMA)/methacrylated gelatin (GelMA) hybrid hydrogels is essential for reproducible multi-batch biofabrication, yet batch effect can severely impair the cross-batch generalization of data-driven models. We established two experimentally measured HAMA/GelMA viscosity datasets collected at different time periods and covering different formulation ranges to characterize batch-effect-induced distributional shifts and support same-batch, cross-batch, and out-of-distribution (OOD) evaluation. Baseline machine learning (ML) models achieved high same-batch predictive performance ( R 2 > 0.90) but degraded markedly under cross-batch conditions ( R 2 = 0.265–0.772). To address these challenges, we propose a physics-informed correction strategy integrating data- and model-level physical priors. A physics-informed data preprocessing (PIDP) strategy filters samples that violate the rheological priors that viscosity increases monotonically with polymer concentration and decreases with temperature. PIDP increased cross-batch R 2 from 0.713 to 0.892 and reduced RMSE by up to 38.8%. A physics-informed neural network (PINN) further improved physical plausibility of the predictions. Integrating PIDP-PINN strategy (IPPS) achieved the best overall performance ( R 2 = 0.898) and reduced OOD errors by 37.7%. The strategy enables more robust and physically consistent hydrogel viscosity prediction for practical biofabrication, providing a transferable route toward reliable modeling and intelligent design of soft polymer materials under realistic experimental variability.
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DOI
高影响因子
Materials Today Bio
·
2026
·
IF 11
Tengfei Ma,Peixuan Wu,Yongning Sheng,Lian Duan,Jie Pei,Yanxin Liu,Kun Fu,Zeyu Liu
Articular cartilage regeneration requires a bioink that combines printability with mechanical support, antibacterial functionality, and pro-chondrogenic bioactivity. Here, a 3D-printable hyaluronic acid methacrylate/polylysine methacrylamide (HAMA/PLMA, HP) hybrid hydrogel incorporating kartogenin-loaded liposomes (KGN@Lipo) was developed for articular cartilage regeneration. Integrated transcriptomic and metabolomic profiling identified HP-associated signatures related to ECM interaction and mechanotransduction, and selected mechanosensitive genes were subsequently validated by qRT-PCR. A second multi-omics comparison showed that KGN@Lipo@HP was associated with attenuated inflammatory–catabolic signaling and a matrix-protective cellular state relative to the Control condition. Physicochemical characterization confirmed rapid photocuring, reliable print fidelity, improved compressive behavior, cyclic resilience, and a tunable porous architecture, while liposomal loading preserved the optimized mechanical baseline. Functionally, KGN@Lipo@HP maintained high cytocompatibility, showed lower intracellular ROS-associated fluorescence, markedly inhibited Staphylococcus aureus growth, and promoted in vitro chondrogenesis, as evidenced by intensified cartilage-matrix staining and increased COL2 and ACAN expression. In the rabbit defect model, KGN@Lipo@HP was associated with the most extensive cartilage-like matrix deposition and the lowest histological scores among the tested groups. Compared with Control, the treated defects also exhibited distinct immunohistochemical profiles for cartilage formation and tissue remodeling. Together, these findings support an HP-based bioink platform that integrates mechanical support, antibacterial protection, and liposomal KGN bioactivity to support a cartilage-permissive regenerative microenvironment.
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DOI
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2025
·
IF 6.6
Wenbi Tuo,Jun Zhao,Xiaoli Yi,Siwei Xiong,Weidong Zhang,Yunzhi Tian,Yingying Du,Yanqing Shu,Yanan He,Yan Qu
Food safety is essential for protecting public health. This study introduces a novel microneedle (MN) patch that employs a pH-responsive colorimetric mechanism for the real-time, easy, and visible detection of meat freshness. The patch is a pH-responsive colorimetric microneedle (C3G/HAMA@MN) patch composed of eco-friendly bio-based components, specifically methacryloylated hyaluronic acid (HAMA) and cyanidin-3-O-glucoside (C3G). Its mechanical strength reaches 7 N per needle, capable of penetrating over 85% of meat tissue. The distinctive structural design allows the microneedle tip to quickly and directly penetrate the meat tissue, extracting interstitial fluid in situ and promptly transferring it to the backing layer. The backing layer visually indicates pH changes in real time. The color change from light to dark matches freshness levels at different deterioration stages. Without sophisticated instruments, consumers may notice the patch's color change in two minutes using their vision, allowing for simple and reliable food quality inspection. A powerful new instrument for on-site food safety monitoring combines real-time display, easy interpretation, and biodegradable materials.
研究领域:
食品科学与技术
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传感器与检测技术
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生物医学工程
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智能包装
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环境监测
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产品关联
DOI
高影响因子
RESPIRATORY RESEARCH
·
2026
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IF 5.7
Chen Xiufeng,Liu Xiuxiu,Jiang Yonghong,Li Wen,Lin Yan,Wang Mingjing,Zhang Hongyu,Chen Mengjie,Lv Tuochen,Lu Yi,Jiang Zhiyan
Objectives To investigate the potential of hyaluronic acid (HAMA) loaded with quercetin (QT) as named (HAMA@QT) nanoparticles, synthesized via microfluidic technology, to reverse epithelial-mesenchymal transition (EMT) in chronic bronchial asthma by modulating macrophage polarization. Methods HAMA@QT nanoparticles were synthesized by encapsulating quercetin (QT) within a HAMA matrix using a microfluidic technique. The nanoparticles were characterized by various techniques, including scanning electron microscopy (SEM), dynamic light scattering (DLS), and X-ray photoelectron spectroscopy (XPS). HAMA@QT in vitro effects were assessed in BEAS-2B cells, while HAMA@QT in vivo therapeutic potential was evaluated in a chronic allergic asthma mouse model. Various assays such as wound healing, Transwell migration, and immunofluorescence were conducted to analyze EMT reversal, macrophage polarization, and cell viability. Additionally, histological and biochemical analyses were performed to assess pulmonary inflammation and fibrosis in the mouse model. Results HAMA@QT nanoparticles exhibited successful encapsulation of quercetin, with high encapsulation efficiency (81.4%) and a sustained drug release profile. In vitro, HAMA@QT significantly reversed LPS-induced EMT in BEAS-2B cells, as evidenced by enhanced migration, increased E-cadherin expression, and decreased Vimentin and α-SMA levels. In vivo, HAMA@QT treatment reduced airway inflammation, mucus secretion, and fibrosis in an asthma mouse model. Furthermore, HAMA@QT nanoparticles promoted M2 macrophage polarization, indicated by increased CD206 expression and reduced iNOS levels, while alleviating inflammation. The nanoparticles effectively reversed EMT in lung tissue by restoring E-cadherin expression and reducing Vimentin and α-SMA in the treated animals. Conclusion HAMA@QT nanoparticles reverse EMT and regulate macrophage polarization in chronic bronchial asthma, alleviate airway inflammation and fibrosis, and represent a promising therapeutic strategy for chronic asthma treatment.
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DOI
高影响因子
ACS Applied Bio Materials
·
2025
·
IF 4.7
Zhichao Zhang,Xijing Zhuang,Xufeng Dong,Jingyuan Zhao,Hao Zhang,Hong Zheng,Chang Xu
The moist wound environment of the human body immediately following injury is highly susceptible to microbial colonization and subsequent infection, potentially triggering a prolonged inflammatory response. Existing dressings tend to be more monofunctional, making it difficult to cope with wound bleeding and bacterial growth at the same time. The development of more effective wound dressings is a critical priority in contemporary wound care. In this study, we developed a hydrogel wound dressing comprising two components: (1) antimicrobial particles of curcumin (Cur)-loaded bimetallic organic framework (Cu/ZIF-8), and (2) a carrier hydrogel formed by methacryloylated gelatin (GelMA) cross-linked with methacryloylated hyaluronic acid (HAMA). The experimental results confirmed the successful loading of curcumin with 45.6% for Cu/ZIF-8@Cur. In addition, the material exhibits pH-responsive behavior, excellent biocompatibility (>80% cell survival), low hemolytic activity (<5%), and potent antimicrobial activity (≥99%) against E. coli and S. aureus. It is stable under neutral conditions and releases bactericidal particles under bacterial infection (in an acidic environment) to achieve sterilization. This study addresses the limitations of gelatin-based dressings, such as inadequate hemostatic capacity and weak antimicrobial performance, and it demonstrates promising potential for clinical translation.
研究领域:
生物材料
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伤口愈合
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纳米技术
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抗菌治疗
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组织工程
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Genjiang Zheng,Chen Yang,Wei Yu,Ye Tian,Zeng Xu,Jia Liu,Shatong He,Yunhao Wang,Zhihao Yue,Xiaodong Wu,Hongyu Zhou,Bo Hu,Wei-En Yuan,Huajiang Chen
Paralysis resulting from spinal cord injury (SCI) arises from the limited regenerative capacity of axons. Mechanical factors have recently emerged as crucial regulators of axon regeneration, complementing or even surpassing chemical cues. In this study, we demonstrated that extracellular matrix stiffness, a key mechanical signal, not only modulated the regenerative capacity of neuronal axons in spinal cord with aging, but significantly fine-tuned axon pathfinding through negative-durotaxis pattern. So, it is imperative to develop a scaffold with biomimetic mechanical guidance properties to promote neural axon regeneration after SCI. Strikingly, inspired by the robust adhesive mechanism of mussels, we developed a facile strategy to synthesize catechol-modified HAMA hydrogel (HAMA@CA) that mimics native spinal cord tissue properties, effectively modulates the biomechanical microenvironment, enhances tissue–implant adhesion, and ultimately promotes spinal cord integration after SCI. Mechanistically, HAMA@CA hydrogel regulates neuronal axon pathfinding following a negative durotaxis pattern, coinciding with changes in mechanosensitive signaling and actomyosin contractility via the Piezo1/RhoA/MLC pathway. RNA-seq analysis also confirms mechanical-mediated SCI repairing by HAMA@CA. These results demonstrates that HAMA@CA rationally combined with mechanical and biochemical cues create promising tissue-engineered strategies to facilitate the repair of SCI. This innovative strategy holds significant promise for future clinical applications in the field.
研究领域:
神经科学
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生物医学工程
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组织工程
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机械生物学
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再生医学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）