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COLLOIDS AND SURFACES B-BIOINTERFACES · 2022 · IF 5.999

Electrochemical deposition of Ppy/Dex/ECM coatings and their regulation on cellular responses through electrical controlled drug release

Chengwei Wu,Xuzhao He,Yifei Zhu,Wenjian Weng,Kui Cheng,Daming Wang,Zuobing Chen

Bone tissue engineering requires a material that can simultaneously promote osteogenic differentiation and anti-inflammatory effects at specific times in response to a series of problems after bone implantation. In this study, the porous network-like titanium matrix was constructed and polypyrrole/dexamethasone (Ppy/Dex) composite coatings with three-dimensional nano-network structure were prepared by electrochemical deposition . The biocompatibility of the composite coatings was further improved by the composite of the extracellular matrix (ECM). The Ppy/Dex/ECM composite coatings released Dex by changing the redox state of Ppy under the electrical stimulation of negative pulses, achieving a drug release controlled by electric field. In terms of osteogenic differentiation, the Ppy/Dex/ECM composite coatings exhibited the best osteogenic activity under electrical controlled release, indicating the synergistic effect of Dex and ECM on osteogenic differentiation. In terms of anti-inflammatory properties, ECM exhibited simultaneous inhibition of both pro- and anti-inflammatory process, while Dex demonstrated significant promotion of anti-inflammatory processes. In this work, the effect of electrical controlled drug release on osteogenic differentiation and inflammation in the ECM cell microenvironment was achieved by preparing Ppy/Dex/ECM composite coatings, which is of great significance for bone tissue engineering and regenerative medicine.

研究领域: 材料科学 · 生物医学工程 · 组织工程 · 再生医学 · 生物材料
✓ 已验证 DOI PubMed 高影响因子
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Collagen and Leather · 2026 ·Vol. 8 ·期 1 ·23 · IF 10.1

Triple-helical recombinant humanized type I collagen promotes photodamaged skin repair via ECM remodeling and anti-inflammatory mechanisms

Wei Nannan,Zhang Yuchen,Huang Wenjie,Tian Xinyu,Yao Linyan,Xiao Jianxi

Ultraviolet (UV) irradiation is a major cause of photoaging, driving oxidative stress, inflammation, and extracellular matrix (ECM) degradation. Collagen is central to dermal integrity, yet animal-derived sources pose immunogenic and pathogen risks, while recombinant collagens reported to date often lack the stable triple-helical architecture required for bioactivity. Here, we present a triple-helical recombinant humanized type I collagen (THRCI) that combines native-like conformation with excellent biosafety and regenerative efficacy. THRCI supported fibroblast adhesion, proliferation, migration, and collagen synthesis, while suppressing intracellular reactive oxygen species and pro-inflammatory cytokines. In zebrafish, THRCI reduced oxidative stress and alleviated UV-induced caudal fin atrophy. In a murine model of acute UV photodamage, topical THRCI accelerated epidermal recovery, restored hydration and barrier function, increased dermal density, and promoted collagen fiber remodeling, while downregulating IL-6 , IL-1β , MMP-1 , and MMP-9 . Collectively, these findings indicate that THRCI exhibits effective photodamage-repair properties in our established models and represents a promising animal-free collagen biomaterial for skin regeneration. Graphical The alternative text for this image may have been generated using AI.

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Cell Reports Medicine · 2025 · IF 10.6

Inhibiting NEDD4 in triple-negative breast cancer cells reprograms tumor immune microenvironment via the β-TrCP/YAP/ECM axis

Nan Su,Wenhua Lian,Baoding Zhang,Yuan Tian,Linying Li,Yiyu Chen,Xiang Zhi,Taoling Zeng,Qiao Wu,Lanfen Chen,Dawang Zhou,Hong-Rui Wang,Shih-Chin Cheng,Li Li,Xianming Deng

Tumor immune microenvironment greatly influences triple-negative breast cancer (TNBC) progression. Identifying targets to convert “cold” tumors into “hot” tumors holds promise for improving treatment outcomes. Here, we show that high expression of NEDD4, an HECT-type E3 ubiquitin ligase, correlates with poor prognosis and reduced CD8 + T cell infiltration in TNBC patients. NEDD4 depletion in TNBC cells significantly inhibits tumor growth through enhancing CD8 + T cell-mediated cytotoxicity in immunocompetent hosts. Mechanistically, NEDD4 depletion stabilizes β-TrCP, leading to YAP ubiquitination and degradation. Downregulated YAP reprograms the immunosuppressive tumor extracellular matrix (ECM) to increase CD8 + T cell infiltration. Furthermore, a small-molecule inhibitor of NEDD4, XMU-MP-10, exhibits significant in vivo efficacy in inhibiting TNBC tumor growth by enhancing CD8 + T cell infiltration in mouse models. Collectively, our findings suggest that the genetic depletion or pharmacological inhibition of NEDD4 enhances antitumor immune responses via the β-TrCP/YAP/ECM cascades, offering a promising therapeutic strategy for TNBC treatment.

CAS / MDL: 127-19-5
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Nature Communications · 2025 ·Vol. 16 ·期 1 ·1-22 · IF 15.7

Injectable ECM-mimetic dynamic hydrogels abolish ferroptosis-induced post-discectomy herniation through delivering nucleus pulposus progenitor cell-derived exosomes

Wang Wenkai,Cheng Zhuo,Yu Miao,Liu Ke,Duan Hongli,Zhang Yang,Huang Xinle,Li Menghuan,Li Changqing,Hu Yan,Luo Zhong,Liu Minghan

Discectomy-induced ferroptosis of nucleus pulposus cells (NPCs) contributes to postoperative lumbar disc herniation (LDH) recurrence and intervertebral disc degeneration (IDD). We discover that nucleus pulposus progenitor cells (NPPCs) could imprint ferroptosis resistance into NPCs through exosome-dependent intercellular transmission of miR-221-3p. Based on these findings, we first develop synthetically-tailored NPPC-derived exosomes with enhanced miR-221-3p expression and NPC uptake capacity, which are integrated into an injectable hydrogel based on extracellular matrix (ECM) analogues. The ECM-mimetic hydrogel (HACS) serves as a biomimetic filler for the post-operative care of herniated discs, which could be facilely injected into the discectomy-established nucleus pulposus (NP) cavity for localized treatment. HACS-mediated in-situ exosome release in the NP cavity enables marked ferroptosis inhibition in NPCs that not only prevents LDH recurrence but also reverses the IDD symptoms, leading to robust restoration of NP structure and functions. In summary, this study offers a promising approach for treating disc herniation.

研究领域: 医学 · 生物材料学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Bone marrow microenvironment-targeted yolk-shell nanoparticle enhances acute myeloid leukemia chemotherapy by preventing endothelial cell/ECM-mediated adhesion

Shiyi Hong,Pei Peng,Yutian Huang,Siying Cai,Cao Yao,Tongtong Huang,Yulu Ying,Wei Li,Yang Xiong,Mancang Gu,Guilin Cheng,Chaofeng Mu

Leukemic cell adhesion to the vascular endothelium and extracellular matrix (ECM) in the bone marrow is a major determinant for frequent drug resistance and relapse in acute myeloid leukemia (AML) chemotherapy. Here, we found that blocking cell–cell and cell-ECM adhesion with DSS6 peptide-modified ginsenoside Rh2 (Rh2) /LOXL2 inhibitor (LX2i) co-loaded yolk-shell nanoparticles (DSS6-NPs) greatly improve the AML chemotherapeutic efficacy. We constructed a collagen I/PEG-PLGA NP with a unique yolk-shell structure to encapsulate hydrophilic LX2i in the collagen I hydrogel-formed yolk, and hydrophobic Rh2 in the PLGA shell. Rh2 in yolk-shell NP reduces AML cell retention in heterotypic spheroids via inhibiting AML cell adhesion to endothelial cells. LOXL2 inhibition prevents contact-dependent interactions between AML cells and ECM. Targeting bone marrow microenvironment-driven adhesion with Rh2/LX2i NPs sensitizes AML cells to cytarabine treatment in a 3D vascularized hydrogel model in vitro . The combination of cytarabine and Rh2/LX2i DSS6-NPs restores the competitive advantage of hematopoietic stem cells over leukemic stem cells, and remodels collagen crosslinking to increase NP penetration in the bone marrow in vivo . Rh2/LX2i DSS6-NPs significantly enhanced the efficacy of cytarabine in a murine AML model. This study provides an effective strategy for developing bone marrow microenvironment-targeted therapeutics for improving AML chemotherapy.

CAS / MDL: 147-94-4 78214-33-2
研究领域: 肿瘤学 · 药剂学 · 分子生物学
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INTERNATIONAL IMMUNOPHARMACOLOGY · 2024 · IF 4.8

circSLTM knockdown attenuates chondrocyte inflammation, apoptosis and ECM degradation in osteoarthritis by regulating the miR-515-5p/VAPB axis

Rijiang Chen,Yan Tong,Xiunian Hu,Wantao Wang,Fake Liao

Osteoarthritis (OA) is a prevalent joint disorder characterized by cartilage degeneration. Circular RNAs (circRNAs) have emerged as pivotal players in OA progression, orchestrating various biological processes such as proliferation, apoptosis, inflammation, and extracellular matrix (ECM) reorganization. Among these circRNAs, circSLTM exhibits aberrant expression in OA, yet its precise regulatory mechanism remains elusive. This study aimed to elucidate the regulatory mechanisms of circSLTM in OA pathogenesis, with a focus on its role as a competing endogenous RNA (ceRNA). Human cartilage tissues were procured from both OA patients and non-OA individuals, while human chondrocyte cells were subjected to lipopolysaccharide (LPS) treatment to mimic OA-like conditions. Our findings revealed upregulation of circSLTM in OA patients and LPS-treated chondrocytes. Loss-of-function assays were conducted, demonstrating that silencing circSLTM via shRNAs mitigated LPS-induced effects on chondrocytes, as evidenced by enhanced proliferation, reduced apoptosis, and inflammatory factors, and altered expression of extracellular matrix proteins. Further exploration into the regulatory mechanism of circSLTM unveiled its interaction with microRNA-515-5p (miR-515-5p) to modulate vesicle-associated membrane protein (VAPB) expression in chondrocytes. VAPB, also upregulated in OA, was positively regulated by circSLTM. Rescue assays corroborated that VAPB overexpression reinstated the protective effects of circSLTM knockdown on LPS-treated chondrocytes. Moreover, concurrent knockdown of both circSLTM and VAPB demonstrated synergistic protection against LPS-induced chondrocyte injury. Additionally, we delineated that LPS triggered the activation of the NF-κB pathway in chondrocytes, which was counteracted by circSLTM silencing. To assess the effects of circSLTM on OA in vivo, anterior cruciate ligament transection (ACLT) mouse models were established, revealing that circSLTM deficiency ameliorated cartilage defects in vivo . In conclusion, circSLTM exacerbates osteoarthritis progression by orchestrating the miR-515-5p/VAPB axis and activating the NF-κB pathway, providing novel insights for targeted therapy in OA management.

CAS / MDL: 298-93-1
研究领域: 医学研究 · 分子生物学 · 骨科 · 细胞生物学
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Biomaterials Research · 2026 · IF 9.8

Construction of a Bioactive ECM Interface Enables Concurrent Suppression of Foreign Body Reaction, Inflammation, and Promotion of Urethral Regeneration

Peihong Han,Xinyu Le,Shutong Li,Kai Fu,Xiuhong Sun,Rui Zhou,Yuqing Niu

The development of tissue-engineered urethral grafts (TEUGs) remains challenged by significant hurdles, particularly in overcoming intraurethral stricture. A core issue is the foreign body reaction (FBR) induced by the implant, which impairs the integration of TEUGs with the autologous urethra. This study employed a tissue-engineered cellularization strategy to construct a stable, hydrophilic, and elastic bioactive extracellular matrix (ECM) interface on the scaffold surface. This interface effectively resists FBR and enhances TEUG integration with host tissues. We developed an “autologous” cellularized TEUG by combining rabbit-derived smooth muscle cells and endothelial cells with nanofiber scaffolds in vitro. After seeding, the cells attached to the scaffold, synthesized, and deposited ECM, thereby fine-tuning the scaffold’s biophysical and biochemical properties. Specifically, glycosaminoglycans (GAGs) in the ECM enhanced scaffold hydrophilicity, while collagen and elastin regulated its elasticity. In a rabbit model of full-thickness urethral defect, GAGs in TEUGs induced a pro-regenerative immune response, characterized by up-regulated expression of arginase 1, CCAAT/enhancer-binding protein β, and tissue inhibitor of metalloproteinase 1 genes and down-regulated expression of matrix metalloproteinase 9 and interleukin-12 genes. This M2 macrophage-dominated gene expression profile further activated the Th2 signaling pathway, promoting the reconstruction of damaged vascular networks, the ordered proliferation of new tissues, the replacement of original ECM, load transmission in new tissues, and the maturation of functional structures. This study provides a simple yet effective strategy to enhance the patency, urine transport capacity, synchronous contraction, and directional contractile function of TEUGs by engineering a bioactive ECM interface endowed with anti-inflammatory and anti-FBR properties.

CAS / MDL: 75-89-8 920-66-1
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Biomedical Materials · 2023 · IF 4

An ECM-mimicking assembled gelatin/hyaluronic acid hydrogel with antibacterial and radical scavenging functions for accelerating open wound healing

Xuebin Ma,Wenli Ning,Yiming Geng,Huarong Shao,Yang Liu,Fei Liu,Daizhou Zhang,Bo Chi,Yali Hou,Xiao Fu

A multifunctional hydrogel dressing with hemostatic, antibacterial, and reactive oxygen species (ROS)-removing properties is highly desirable for the clinical treatment of open wounds. Although many wound dressings have been prepared, the modification of polymers is often involved in the preparation process, and the uncertainty of biological safety and stability of modified polymers hinders the clinical application of products. In this study, inspired by the composition and crosslinking pattern of extracellular matrix (ECM), a deeply ECM-mimicking multifunctional hydrogel dressing is created. Tannic acid (TA) and poly-ε-lysine (EPL) are added into a gelatin/hyaluronic acid (Gel/HA) matrix, and a stable hydrogel is formed due to the formation of the triple helix bundles of gelatin and hydrogen bonds between polymers. The introduction of TA and EPL endows the ECM-mimicking hydrogel with stable rheological properties, as well as antibacterial and hemostatic functions. The as-produced hydrogels have suitable swelling ratio, enzyme degradability, and good biocompatibility. In addition, it also shows a significant ability to eliminate ROS, which is confirmed by the elimination of DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical. Full-thickness skin wound repair experiment and histological analysis of the healing site in mice demonstrate that the developed ECM-mimicking Gel/HA hydrogels have a prominent effect on ECM formation and promotion of wound closure. Taken together, these findings suggest that the multifunctional hydrogels deeply mimicking the ECM are promising candidates for the clinical treatment of open wounds.

✓ 已验证 DOI PubMed 高影响因子
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Applied Materials Today · 2022 · IF 8.663

Biomimetic macroporous hydrogel with a triple-network structure for full-thickness skin regeneration

Xiaojun Long,Xiao Xu,Deshun Sun,Yi Hong,Caining Wen,Yixin Xie,Bing Yan,Huawei Zhang,Qi Ge,Wencui Li,Li Duan,Hongwei Ouyang,Daping Wang

Full-thickness skin repair is still a challenge in clinical practice because it is extremely difficult for dermal reconstruction and calls for a promising strategy to achieve quick sutureless closure and high-quality dermal restoration for large acute skin defects. Inspired by the unique composition, mechanical properties and microscopic architecture of skin tissue, a novel biomimetic hydrogel with a triple-network structure that mimics the extracellular matrix (ECM) composition has been reported. A composite biomimetic hydrogel was prepared using ECM-derived biopolymers, gelatin methacryloyl (GelMA) and N-(2-aminoethyl)-4-(4-(hydroxymethyl)-2‑methoxy-5-nitro-sophenoxy) butanamide (NB)-linked sodium alginate (Alg-NB) and the photoinitiator lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP). This biomimetic hydrogel can undergo rapid gelling under UV irradiation (approximately 3 s), has strong mechanical properties (mechanical strength ≈530 kPa) with UV-ionic-crosslinking, and shows strong adhesion to wet tissue. In vitro two-dimensional culture of human skin fibroblasts (HSFs) confirmed that the biomimetic hydrogel has excellent biocompatibility, and HSFs on the surface grow into cell clusters because of the macroporous structures of the hydrogel (pore diameter ≈160 μm). The subcutaneous implantation of the biomimetic hydrogel in Sprague-Dawley (SD) rats confirmed its biocompatibility and low biodegradation in vivo. Moreover, in an SD rat full-thickness skin defect model, this engineered biomimetic hydrogel not only could be used for sutureless wound closure strategies but also could accelerate the reconstitution of dermal tissue with skin appendages. This study provides an effective strategy of quick sutureless wound closure and highly efficient repair for full-thickness skin defects and shows enormous potential for tissue regeneration in clinical applications.

研究领域: 组织工程 · 生物材料科学 · 再生医学
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Synergistic ECM-TTPBr/PCBA Dual-Molecule Buried-Interface Passivation Enables Highly Efficient Planar Carbon-Based HTL-Free Perovskite Solar Cells

Zhiyang Ju,Wenyan Zhao,Wenying Jiang,Chuanjin Tian,Yumin Liu,Chang-an Wang,Zhipeng Xie,Jionghua Wu

This work proposed a novel strategy utilizing ethoxycarbonyl triphenylphosphonium bromide (ECM-TTPBr) as a copassivator, which significantly improves the solubility of [6,6]-phenyl-C61-butyric acid (PCBA) in chlorobenzene solution to enable uniform coverage of PCBA on the TiO2 electron transport layer (ETL). The dual-molecule copassivation effect optimizes the interface between the ETL and perovskite layer by reducing interface defects and enhancing ETL conductivity to improve charge extraction and transport efficiency at the interface, while effectively decreasing residual lead iodide clusters at the perovskite film’s bottom interface to smooth the interface and significantly improve physical contact between the perovskite layer and ETL. Owing to this dual interface passivation, the device achieves a photovoltaic conversion efficiency of 19.15% with notably enhanced stability, offering a technically feasible pathway with industrialization potential for developing high-efficiency and stable hole transport layer-free carbon-based perovskite solar cells.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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EUROPEAN JOURNAL OF PHARMACOLOGY · 2026 · IF 5.7

β-Myrcene alleviates atopic dermatitis-like inflammation and is associated with ECM–FAK/Src–YAP signaling during epidermal barrier repair

Nana Long,Youwei Zuo,Jian Li,Renxiu Yao,Xiao Zhang,Hongping Deng

Background Atopic dermatitis (AD) is characterized by epidermal barrier impairment and immune-driven inflammation. Strategies that restore barrier architecture while constraining inflammation are of therapeutic interest. Purpose To evaluate the barrier-reparative and anti-inflammatory effects of β-myrcene (MYR) in experimental atopic dermatitis and to investigate whether ECM–FAK/Src–YAP signaling is associated with these effects. Methods A 2,4-dinitrochlorobenzene (DNCB)-induced murine model of AD-like dermatitis was evaluated by transepidermal water loss (TEWL), histopathology, dermal collagen organization, filaggrin (FLG) immunofluorescence, and circulating inflammatory mediators. Integrated skin transcriptomic and proteomic analyses and public human AD transcriptomic datasets were used to identify MYR-associated pathways. In primary human keratinocytes stimulated with tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), YAP localization, FAK Tyr397 and Src Tyr416 phosphorylation, YAP/TAZ target genes, barrier markers, and inflammatory outputs were assessed. Peptide 17 was used to examine the contribution of YAP-dependent transcription. Results MYR reduced dermatitis severity and epidermal hyperplasia, lowered TEWL, partially restored FLG immunofluorescence, and preserved dermal collagen organization in DNCB-challenged mice. Multi-omics profiling identified MYR-associated changes in extracellular matrix (ECM)–receptor interaction, focal adhesion, cytoskeletal remodeling, epidermal differentiation, and immune-related programs. In inflamed keratinocytes, MYR was associated with increased FAK and Src phosphorylation, YAP nuclear accumulation, CCN1/CCN2 expression, and barrier-marker expression, together with reduced inflammatory mediator production. Peptide 17 attenuated MYR-associated YAP nuclear accumulation and several downstream transcriptional responses. These findings support the participation of YAP-dependent signaling but do not establish MYR as a direct regulator of FAK, Src, or YAP or demonstrate a strictly linear signaling sequence. Conclusion MYR produced barrier-restorative and anti-inflammatory effects in experimental atopic dermatitis. The results identify ECM–FAK/Src–YAP signaling as a candidate pathway associated with the MYR response, with pharmacological inhibition providing partial functional evidence for a YAP-dependent component. Download: Download high-res image (265KB) Download: Download full-size image

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Bioactive Materials · 2025 · IF 20.3

Sequential construction of vascularized and mineralized bone organoids using engineered ECM-DNA-CPO-based bionic matrix for efficient bone regeneration

Tingting Gai,Hao Zhang,Yan Hu,Ruiyang Li,Jian Wang,Xiao Chen,Jianhua Wang,Zhenhua Chen,Yingying Jing,Chenglong Wang,Long Bai,Xiuhui Wang,Jiacan Su

Given the limitations of allogeneic and artificial bone grafts, bone organoids have attracted extensive attention for their physiological properties that closely resemble natural bone, offering great potential to bone reconstruction for critical-sized bone defects. Although early-stage bone organoids such as osteo-callus organoids and woven bone organoids have been reported, functional bone organoids with vascularization and mineralization are currently unavailable due to the lack of bone-mimicking matrix and dynamic culture systems suitable for the long-term cultivation of mature bone organoids. Herein, a novel engineered bionic matrix hydrogels with multifunctional components and double network structure are developed by incorporating calcium phosphate oligomers (CPO) into a combination of bone-derived decellularized extracellular matrix (ECM) and salmon-derived deoxyribonucleic acid (DNA) via photo-crosslinking and dynamic self-assembly strategies. This kind of bionic matrix hydrogels facilitate recruitment, proliferation, osteogenesis and angiogenesis of bone marrow mesenchymal stromal cells (BMSCs). More importantly, vascularized and mineralized bone organoids are sequentially constructed using BMSCs-loaded engineered bionic matrix hydrogels via in vitro dynamic culture and in vivo heterotopic ossification. Meanwhile, this kind of engineered bionic matrix are capable of achieving efficient bone repair for cranial defect. These findings suggest that engineered bionic matrix hydrogels combined with such dynamic culture system, providing a promising strategy for functional bone organoids construction.

研究领域: 再生医学 · 组织工程 · 骨科
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