CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Huiwen Zhang,Zhijian Xing,Jingxi Wang,Hongli Luo,Chuanrong Zhao,Zengzilu Xia,Kaiyong Cai
The presence of cancer stem cell (CSC) leads to the failure in triple-negative breast cancer treatment because conventional therapy is hard to prevent CSC proliferation. A multimodal combination therapy strategy by ferroptosis, pyroptosis, and differentiation is proposed to address it. This nano-platform is consisted with metal-phenolic network nanoparticles loading with drug β-Lapachone (MPN@Lap) and nanoparticles encapsulating drug all-trans retinoic acid ( ABS ATRA). On one hand, MPN@Lap nanoparticles effectively enhanced cancer cellular reactive oxygen species (ROS) level by the double circulation of β-Lapachone reduction and Fenton reaction, thereby depleting glutathione for the accumulation of lipid peroxidation and cleaving cysteinyl aspartate-specific proteases 3 for gasdermin E dissociation, further causing the dual activation of ferroptosis and pyroptosis concurrently. On the other hand, all-trans retinoic acid released from ABS ATRA nanoparticles reduced the proportion of stemness-related cell population of CD44 + /CD24 − and the expression of stem cell marker aldehyde dehydrogenase 1 for stemness inhibition. With a high ROS level and the damage of mitochondrial membrane potential, redox homeostasis in CSC is destructed and it further facilitated and amplified the differentiation process. Studies demonstrated that this dual-action approach synergistically inhibited tumor growth and eradicated CSC stemness by ferroptosis, pyroptosis, and differentiation. Therefore, this study provides a novel cancer cells and CSC dual-acting strategy with multimodal combination approaches of ferroptosis, pyroptosis, and differentiation to combat breast cancer cells, which also offers advice for treating CSC-driven malignancies.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Xiaxia Yang,Lili Wang,Xian Chen,Biyang Ling,Jianxi Xiao
Osteochondral defects pose a significant clinical challenge, requiring the regeneration of both articular cartilage and subchondral bone across a continuous gradient of composition and mechanical properties. Here, we present BioGraOstO, a digital light processing (DLP)-based 3D bioprinted scaffold for constructing biomimetic osteochondral organoids with precisely graded architectures. Three photo-crosslinkable, cell-laden bioinks were engineered to emulate native osteochondral zones: methacrylated type II collagen and hyaluronic acid for hyaline cartilage (HyaC); 30 % mineralized methacrylated type I collagen for calcified cartilage (CalC); and 60 % mineralized methacrylated type I collagen and hyaluronic acid for subchondral bone (SubB). Sequential DLP bioprinting produced multilayered constructs with well-integrated organic-inorganic interfaces, a modulus spanning 1.35–17.29 kPa, minimal swelling (<10 %), and programmable biodegradation over 15 days. The organoids supported region-specific chondrogenic and osteogenic differentiation of bone marrow–derived mesenchymal stem cells (BMSCs) in vitro , confirmed by histology, immunofluorescence, and gene expression. In a rat osteochondral defect model, BioGraOstO implants achieved near-complete restoration of cartilage and subchondral bone within 12 weeks, significantly outperforming acellular scaffolds. This study establishes a versatile and clinically translatable strategy for osteochondral regeneration, leveraging high-resolution DLP bioprinting, graded biomimetic bioinks, and integrated organoid functionality, offering a promising approach for joint repair and next-generation tissue engineering.
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JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Xunqi Zhang,Manning Zhu,Jing Guo,Jian Cao,Juanjuan Zheng,Jiahe Wu,Weihang Zhou,Xinchi Jiang,Nan Wang,Jiafu Mu,Tianchen Huang,Jian-Qing Gao
Spinal cord injury (SCI) requires sufficient and sustained therapeutic intervention for microenvironment regulation in the acute phase. However, systemic drug administration is often ineffective due to non-specific distribution within the damaged spinal cord. While local implantation systems have gained attention for site-specific delivery, they are often constrained by spatial limitations and present challenges in designing sequential release profiles. Herein, we reported the development of a composite drug delivery system integrating intranasal administration with local implantation. Specifically, the locally implanted scaffold was modified with dibenzocyclooctyne (DBCO) groups (dGN). Azide group-functionalized nanovesicles (aNVs), extruded from engineered mesenchymal stem cells, were continuously administered intranasally. aNVs accumulated within the lesion by undergoing a bio-orthogonal click chemistry reaction with dGN, which markedly enhanced their local distribution and retention. The composite drug delivery system, dGN&aNVs, effectively promoted acute microenvironmental regulation, hindlimb motor function recovery, associated symptoms alleviation, and tissue repair and regeneration following SCI in rats. This work presents a robust and minimally invasive platform designed for the precision-targeted therapy of central nervous system diseases.
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Biomaterials Advances
·
2025
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IF 6
Xinna Qiu,Qiu Zhao,Yue Yu,Danyang Song,Yu Song,Wenfei Wang,Xiaogang Weng,Zhonghua Liu,Tingsheng Yan
The key pathological determinants of impaired healing in chronic diabetic wounds are angiogenic dysfunction and microenvironmental dyshomeostasis. To address the critical need for multifunctional therapeutic platforms, we developed an intelligent hydrogel dressing (DFO@G/C-CO) through dynamic Schiff base crosslinking of carboxymethyl chitosan and oxidized pectin, integrated with deferoxamine(DFO)-loaded composite microspheres. The pH-responsive hydrogel demonstrated accelerated DFO release kinetics under acidic conditions, mimicking the diabetic wound microenvironment, ensuring targeted therapeutic delivery. In vitro analyses revealed that DFO@G/C-CO significantly enhanced human umbilical vein endothelial cell (HUVEC) migration and angiogenesis via hypoxia-mimetic HIF-1α stabilization and subsequent upregulation of VEGF and CD31. In diabetic mouse full-thickness skin defect models, the hydrogel treatment group achieved a 95 % wound closure rate within 15 days, with histological analysis showing significantly increased collagen deposition and neovascular density compared to controls. Mechanistic studies revealed that the hydrogel activated the PI3K-Akt signaling axis by upregulating HIF-1α/VEGF expression, synergistically enhancing angiogenesis and cellular proliferation. The DFO@G/C-CO hydrogel developed herein integrates antibacterial, angiogenic, and microenvironment-modulating functionalities, enabling efficient diabetic wound healing and representing a novel therapeutic paradigm for managing chronic diabetic wounds.
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ACS Applied Materials & Interfaces
·
2025
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IF 8.2
Zhuojun Xie,Mengqi Luo,Wenjie Zhang,Liming Ge,Changdao Mu,Defu Li,Zhilang Xu,Ye Tian,Xianglong Han
Infectious bone defects (IBDs) pose a significant clinical challenge due to the simultaneous requirements for effective infection control and robust bone regeneration, and guided bone regeneration (GBR) using multifunctional scaffolds offers a promising therapeutic strategy. Herein, we developed a bilayer hydrogel scaffold (DSHM) based on methacrylated silk fibroin (SilMA) integrated with hydroxyapatite (HA) and minocycline hydrochloride (MH) to address these demands. By precisely optimizing the concentrations of SilMA, photoinitiator, HA, and MH, we engineered a bilayer structure featuring a porous HA-loaded layer (PSH, ∼432.1 μm) to enhance mechanical strength and support osteogenic differentiation and a dense MH-loaded layer (DSM, ∼34.6 μm) to act as a barrier against fibrous tissue ingrowth and provide sustained antibacterial effects. The interface-cross-linked DSHM scaffold exhibited a well-defined heterogeneous architecture, improved mechanical properties, tunable degradation, and excellent biocompatibility. Notably, the DSHM demonstrated synergistic multifunctionality, including inhibition of fibroblast infiltration, promotion of bone tissue regeneration, and effective infection control. Overall, the DSHM scaffold presents a robust approach for the localized and targeted treatment of IBDs, with strong potential for clinical translation.
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Materials Today Bio
·
2025
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IF 10.2
Jianwei Li,Mengkun Wang,Xiangzhong Tan,Yingxi Duanmiao,Xiang Zheng,Zhen Wang,Fei Gao,Yuqing Miao,Huipeng Li,Bo Liu,Mingjun Li,Tingbin Zhang,Huan Zhou,Jinfeng Xing,Lei Yang
The treatment of chronic diabetic wounds faces considerable challenges owing to complex environments in the wound bed, such as chronic inflammation, excessive reactive oxygen species (ROS), impaired extracellular matrix (ECM) and bacterial infection. Current strategies, including bandages, hydrogel dressings and medical devices, that focus solely on a few pathological features have limited success. Herein, a fast self-gelling polyacrylic acid (PAA) derivative/madecassoside (MA) particulate dressing with anti-inflammatory, antioxidative, collagen deposition-promoting and intrinsic antibacterial properties is developed to simultaneously regulate the wound microenvironment and promote tissue regeneration in infected diabetic wounds. The incorporation of N-[Tris(hydroxymethyl)methyl]acrylamides (THMA), a small molecule compound that has three hydroxy groups clustered together, into the PAA backbone confers the copolymer with self-gelation, robust wet tissue adhesion and a strong capacity to load MA via multiple hydrogen bonding. The developed dual-component particulate dressing effectively regulated macrophage polarization towards the anti-inflammatory phenotype, and displayed potent antibacterial activity against both Gram-positive S. aureus (99.2 %) and Gram-negative E. coli (90.8 %) at a dose of 8 mg mL −1 . Further, the dressing obviously accelerated the healing of full-thickness skin wounds compared with commercial fibrin glue in a S. aureus -infected diabetic mouse model. This multifunctional PAA-based wound dressing is potentially valuable for clinical applications towards diabetic foot ulcers, pressure ulcers and other conditions of acute or chronic wounds.
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Advanced Healthcare Materials
·
2025
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IF 9.6
Xiaoliang Qi,Yulong Lan,Jing Chen,Yajing Xiang,Yingying Wang,Liting Jiang,Yujie Dong,Jiaxin Li,Zhiyong Liao,Zhangping Li,Jianliang Shen
Current guidelines for addressing multidrug-resistant bacteria-infected diabetic foot ulcers (DFUs), a leading cause of disability and death among diabetes sufferers, still lack specificity. Such DFU lesions often experience delayed recovery, primarily due to the bacteria-induced inflammation in the adverse diabetic microenvironment. Here, an endogenous adenosine triphosphate (ATP)-responsive hydrogel prodrug platform (abbreviated as HSAQ3), which embeds hemoglobin@zeolitic imidazolate framework-8 (Hb@ZIF-8) nanoparticles in a prodrug (1-naphthylacetic acid, NAA)-loaded biopolymer matrix, targeting multidrug-resistant bacterial infections in DFUs is presented. Initially, using a simple local injection, an HSAQ3 adhesive barrier triggered by UV light is applied to the wound. Concurrently, HSAQ3's composition, enriched with quaternary ammonium salt and phenylboronic acid groups, exhibits strong bacterial trapping capabilities, effectively capturing bacteria at the wound location within the hydrogel. Following this, ATP secreted by bacteria initiates the degradation of Hb@ZIF-8, enabling the simultaneous interaction of the encapsulated NAA prodrug with Hb peroxidase. This process effectively produces reactive oxygen species (ROS) in situ, addressing their limited lifespan and diffusion range, thus guaranteeing a highly efficient bactericidal effect. This study unveils an innovative inorganic–organic hybrid prodrug system, leveraging endogenous ATP from bacteria for precise ROS generation, enhancing the healing of multidrug-resistant bacterial infections in DFUs.
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Pharmaceutics
·
2025
·Vol. 17
·期 6
·690
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IF 5.5
Yingchao Yang,Jingyi Chen,Shengming Wang,Yaxin Zhu,Yao Wang,Yan Chen,Mingjiang Xia,Ming Yang,Hongliang Yi,Kaiming Su
Objectives: Nasal mucosa wound healing faces challenges such as acidic microenvironments and bacterial proliferation. Persistent mucosal defects predispose to complications such as nasal septal perforation. Conventional drug delivery systems suffer from nonspecific release and short-term efficacy. This study aimed to develop a pH-responsive liposome-hydrogel composite (HYD-Lip/DXMS@HG) to integrate pH-triggered dexamethasone (DXMS) delivery, antifouling properties, and mechanical support for refractory injuries.Methods: The composite combined acylhydrazone-modified liposomes with a hydrogel synthesized from hydroxyethylacrylamide (HEAA) and diethylacrylamide (DEAA). In vitro assays evaluated DXMS release kinetics, RPMI 2650 cell migration/proliferation, and antibacterial properties. In vivo rabbit nasal mucosal injury models assessed healing efficacy via histology analyses. RNA sequencing was performed to identify key signaling pathways.Results: HYD-Lip/DXMS@HG exhibited sustained DXMS release in acidic conditions, accelerating cell migration/proliferation in vitro. In rabbits, the composite reduced TNF-αexpression and CD45+ leukocyte infiltration, while enhancing collagen alignment and epithelial thickness. RNA sequencing identified upregulated ECM receptor interaction, Hippo, TGF-β, and PI3K-Akt pathways, linked to collagen remodeling, anti-apoptosis, and angiogenesis.Conclusions: This multifunctional platform synergizes pH-triggered drug delivery, mechanical support, and antibacterial activity, offering a promising therapeutic strategy for refractory nasal mucosal injuries and postoperative recovery.
研究领域:
药剂学
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生物医学工程
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组织工程
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ACS Applied Materials & Interfaces
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2025
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IF 8.2
Zheng Wang,Feng Xu,Di Wu,Wei Huang,Zhiqin Chu,Yuan Lin
Cells need to migrate through confined spaces during processes such as embryo development and cancer metastasis. However, the fundamental question of how confinement size and surrounding rigidity collectively regulate the migration capability of cells remains unclear. Here, by utilizing maskless photolithography with a digital micromirror device (DMD), a microchannel with precisely controlled width and wall stiffness (similar to those exhibited by natural tissues) is fabricated. We find that increasing the rigidity of the confining wall leads to a more reduced nuclear volume but has no detectable influence on the myosin expression level in the cells. More interestingly, a biphasic trend of the cell speed is observed, with the migration velocity reaching its minimum at an intermediate wall rigidity of ∼10 kPa. A motor-clutch-based pulling race model is then proposed, which suggests that such biphasic dependence is due to the fact that a very soft channel wall will result in small deformation of the nucleus and consequently reduced cell-wall friction, while larger myosin-based crawling force can be triggered by a stiff confining boundary, both leading to a relatively high migration speed. These findings could provide critical insights into novel strategies for controlling the movement of cells and the design of high-performance biological materials.
研究领域:
细胞生物学
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生物力学
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Journal of Materials Chemistry B
·
2025
·
IF 5.7
Rong Luo,Zhao Chen,Man Zhe,Wenting Wu,Yuzhen Xiao,Jiabao Jiang,Hao Liu,Ming Liu,Fei Xing
The management of bone defects poses a significant challenge for clinicians, necessitating effective strategies to regulate immune inflammation, angiogenesis, and osteogenic differentiation for successful bone regeneration. In this study, we developed a novel hydrogel composed of carboxymethyl chitosan (CMCS) and gelatin methacryloyl (GelMA) designed for the sustained release of the bioactive component calcitonin gene-related peptide (CGRP) and zeolitic imidazolate framework-8 (ZIF-8). CGRP was initially encapsulated within ZIF-8 and subsequently integrated into the CMCS/GelMA hydrogel matrix. In vitro evaluations revealed that the hydrogel exhibited exceptional biocompatibility and antimicrobial properties, effectively promoting osteogenesis and angiogenesis while modulating M2 macrophage polarization. Furthermore, in vivo assessments indicated that the CGRP@MOF/CG hydrogel significantly regulated the local immune microenvironment and accelerated the healing of cranial defects in rat models. This study provides valuable references for the design and fabrication of multifunctional materials for enhancing bone regeneration.
研究领域:
生物材料学
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组织工程学
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再生医学
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CERAMICS INTERNATIONAL
·
2025
·
IF 5.6
Yansong Liu,Yongsheng Liu,Yunlei Lv,Yixin Dong,Yejie Cao,Yanxia Du
Multiscale porous yttria-stabilized zirconia (YSZ) ceramics were fabricated via digital light processing (DLP), employing polymethyl methacrylate (PMMA) microspheres as a pore-forming agent. The evolution of microstructure and properties of ceramics, including compressive strength and thermal conductivity, was systematically investigated. The results showed that the porosity and density of the ceramics were 56.43-3.95% and 2.63-5.82 g/cm 3 , respectively, within the sintering temperature range of 1200-1600 °C. Correspondingly, the compressive strength and thermal conductivity of ceramics were 71.00-315.95 MPa and 0.51-2.68 W/(m·K), respectively. At lower sintering temperatures (≤ 1400 °C), multiscale pores formed inside the ceramics due to the decomposition of photosensitive resin and PMMA microspheres. The existence of multiscale pores further reduced the thermal conductivity by an average of 46.08%. In contrast, at higher sintering temperatures (≥ 1500 °C), the density and the mechanical properties of ceramics were significantly improved. In particular, the increase in porosity depended primarily on the increase in pore-forming agent content when the submicron pores disappeared.
研究领域:
材料科学
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陶瓷
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增材制造
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微观结构分析
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力学性能
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热学性能
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
·
IF 8.5
Xin Zhang,Zhengwei Xu,Hong Zhang,Zhenchun Li,Bo Ren,Bo Wang,Xiaodong Yang,Junqiu Liu
The Janus adhesive wound dressings exhibit properties analogous to human skin. Specifically, they must possess both adhesive and non-adhesive characteristics to function effectively. The adhesive property ensures secure attachment to the wound site, while the non-adhesive side acts as a protective barrier against external contaminants. In this study, we have developed an integrated Janus antibacterial hydrogel that features a rapid photoresponsive adhesive layer alongside a robust anti-adhesive layer. The anti-adhesion layer hydrogel, referred to as PPAL, exhibits a maximum tensile fracture strength of 738.54 kPa and a fracture strain of 774.02 %. This adhesive layer is referred to as MCDAE. Upon irradiation with 405 nm ultraviolet light, MCDAE rapidly forms a strong bond with PPAL within 10 s, resulting in the formation of a Janus-adhesive hydrogel (MCDAE/PPAL). We synthesized silver nanoparticles (AgNPs) with sizes ranging from 20 to 40 nm in situ within MCDAE hydrogels. Owing to the synergistic effects of quaternary ammonium compounds and AgNPs, Janus MCDAE/PPAL hydrogels exhibited concentration-dependent bacteriostatic activity against both Escherichia coli and Staphylococcus aureus . Furthermore, both in vitro and in vivo experiments have demonstrated that the MCDAE/PPAL dressing possesses superior biocompatibility, exceptional antibacterial properties, effective hemostatic capabilities, and enhanced wound healing potential.
研究领域:
生物材料
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生物医学工程
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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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