Materials Science & Engineering C-Materials for Biological Applications最新文献

{"title":"Targeted nanotheranostics mitigates radiation-induced fibrosis to promote immune infiltration and enhance radio-chemotherapy in pancreatic ductal adenocarcinoma","authors":"Arjun Sabu ,&nbsp;Ying-Chieh Yang ,&nbsp;Ritwick Ranjan Sarma ,&nbsp;Lakshminarayan Ramesan ,&nbsp;Yi-Hsuan Lin ,&nbsp;Hsin-Cheng Chiu","doi":"10.1016/j.bioadv.2025.214677","DOIUrl":"10.1016/j.bioadv.2025.214677","url":null,"abstract":"<div><div>Radiotherapy and chemotherapy exhibit limited clinical efficacy in pancreatic ductal adenocarcinoma (PDAC) due to its dense stromal desmoplasia, acting as a physical barrier that hinders drug penetration and immune cell infiltration while also promoting the formation of intratumoral radiation-induced fibrosis (RIF). In the present study, topoisomerase I inhibitor SN-38-loaded mesoporous silica-coated Bi₂O₃ nanoparticles (S-MBO NPs) were prepared and camouflaged with PDAC/red blood cell hybrid membranes loaded with the stromal reprogramming drug all-trans retinoic acid. The nanotherapeutics referred to as (S-MBO@A-RPCM NPs) were found capable of effectively overcoming the stromal barrier, mitigating RIF, and enhancing the radio/chemotherapeutic efficacy against PDAC. Both the <em>in vitro</em> and <em>in vivo</em> studies strongly confirmed the homotypic uptake and homologous targeting ability of S-MBO@A-RPCM NPs. The combined radiosensitizing effects of Bi₂O₃ and SN-38 resulted in enhanced DNA damage in UN-KC-6141 cells, decreased colony formation, and induction of immunogenic cell death by combined chemo/radiotherapy. Biodistribution data of S-MBO@A-RPCM NPs showed enhanced homologous targeting property toward PDAC, attributed to the hybrid membrane coating extracted from erythrocytes and UN-KC-6141 cancer cells on NPs. Importantly, S-MBO@A-RPCM NP treatment was found capable of deactivating the activated pancreatic stellate cells induced by radiation and TGF-β-thereby directly mitigating the fibrogenic activity characteristic of RIF <em>in vitro</em> and <em>in vivo</em>. Significantly reduced expression of α-SMA, collagen I, and fibronectin was observed after the treatment, accounting largely for the disruption of the stroma barrier, chronic inflammation signaling and tumor-stroma crosstalk, resulting in enhanced sensitization of UN-KC-6141 cells to SN-38 and radiation alongside improved immune infiltration. The <em>in vivo</em> data strongly signify that combining radiotherapy with the treatment of S-MBO@A-RPCM NPs exhibits superior tumor microenvironment reprogramming, attenuation of RIF and effective tumor growth inhibition in UN-KC-6141 tumor-bearing mice with minimal side effects.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214677"},"PeriodicalIF":6.0,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145824127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ROS-amplifying HKUST-1 nanozyme for enhanced colon cancer therapy","authors":"Jing Yang ,&nbsp;Jie Wang ,&nbsp;Chao Tao ,&nbsp;Xiaowei Tang ,&nbsp;Liuxuan Yang ,&nbsp;Ke Wang ,&nbsp;Weiyi Chen ,&nbsp;Zhirong Zhong ,&nbsp;Siqiong Wu ,&nbsp;Meiling Zhou","doi":"10.1016/j.bioadv.2025.214671","DOIUrl":"10.1016/j.bioadv.2025.214671","url":null,"abstract":"<div><div>The development of effective strategies to amplify reactive oxygen species (ROS) within tumors has great potential to improve colon cancer therapy. In this study, we developed a multifunctional nanozyme platform (HHOC) based on the copper metal-organic framework HKUST-1, co-loading the photosensitizer chlorin e6 (Ce6) and the chemotherapeutic agent oxaliplatin (OXA), with surface modification by hyaluronic acid (HA). Benefiting from HA-mediated CD44 targeting, HHOC preferentially accumulated in colon cancer cells, resulting in enhanced cellular uptake. Upon laser irradiation, Ce6 generated abundant singlet oxygen to induce photodynamic therapy. Meanwhile, the HKUST-1 nanozyme exhibited peroxidase-like activity, with its Cu²⁺ sites readily reduced by the elevated intracellular glutathione to Cu⁺, which depleted this key antioxidant and impaired cellular redox homeostasis. The generated Cu⁺ further catalyzed endogenous hydrogen peroxide through Fenton-like reactions to produce highly cytotoxic hydroxyl radicals, thereby amplifying ROS-mediated oxidative stress. Moreover, HKUST-1 converted light energy into heat, producing a photothermal effect that promoted tumor cell damage and accelerated drug release. Released OXA exerted chemotherapeutic cytotoxicity, synergizing with ROS-mediated therapies. <em>In vivo</em> studies using CT26 tumor-bearing mice demonstrated that HHOC achieved a tumor growth inhibition rate of 94.51 %, confirming the efficacy of this ROS-amplifying nanozyme platform. This work presents HKUST-1-based nanozyme as an effective approach for multimodal colon cancer therapy through enhanced ROS generation and combinational treatment modalities.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214671"},"PeriodicalIF":6.0,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145865886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzyme-triggered peptide assembly boosts dental stem cell osteogenic differentiation by enhancing osteogenic pentapeptide accumulation","authors":"Zhe Yu ,&nbsp;Xiaoying Liu ,&nbsp;Yao Du ,&nbsp;Haiqin Huang ,&nbsp;Lihui Zhang ,&nbsp;Juanjuan Zhang ,&nbsp;Yan Sun ,&nbsp;Zhitao Wang ,&nbsp;Jingkun Bai","doi":"10.1016/j.bioadv.2025.214670","DOIUrl":"10.1016/j.bioadv.2025.214670","url":null,"abstract":"<div><div>Tooth regeneration and bone tissue repair represent significant challenges in oral surgery, and osteogenic differentiation is crucial with respect to dental implant osseointegration and bone healing. Studies have reported that osteogenic growth pentapeptide (OGP5) promotes the differentiation of bone marrow mesenchymal stem cells into osteoblasts. Owing to their easy availability and multipotent differentiation capabilities, human dental pulp stem cells (hDPSCs) are promising in the context of regenerative medicine and dental therapeutics. However, research on the effects of OGP5 on the differentiation of hDPSCs remains insufficient, and the short half-life and poor targeting of functional small-molecule peptides limit its application. Our findings indicate that OGP5 facilitates the differentiation of hDPSCs into osteoblasts. To increase the efficiency with which OGP5 can induce the osteogenic differentiation of hDPSCs, an amphiphilic peptide (Pep1) with alkaline phosphatase (ALP)-responsive properties was designed and synthesized. The encapsulation of OGP5 led to the self-assembly of OGP5/Pep1 into spherical nanoparticles, which transformed into nanofibers upon ALP induction. Importantly, Pep1 significantly enhanced the accumulation of OGP5 in hDPSCs, thereby promoting the differentiation of hDPSCs into osteoblasts, thus providing a new perspective that can facilitate the development of bone repair and regenerative medicine.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214670"},"PeriodicalIF":6.0,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145865933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Injectable silk fibroin hydrogel encapsulating pH-Responsive ZnS nanoparticles for synergistic redox modulation and diabetic wound healing","authors":"Xi Cheng ,&nbsp;Yuchong Wang ,&nbsp;Jiao Qian ,&nbsp;Rong Bai","doi":"10.1016/j.bioadv.2025.214674","DOIUrl":"10.1016/j.bioadv.2025.214674","url":null,"abstract":"<div><div>Chronic diabetic wounds remain a major clinical challenge due to excessive reactive oxygen species (ROS), persistent inflammation, and impaired cellular function. Current wound dressings offer limited capacity to simultaneously regulate redox imbalance and support tissue regeneration, highlighting the necessity for adaptive, intelligent, and multifunctional platforms for regenerative therapy. Herein, we developed an injectable hydrogel system composed of methacrylated silk fibroin (SilMA) and aqueous-phase, pH-sensitive zinc sulfide nanoparticles (ZnS NPs). Spherical ZnS NPs were synthesized <em>via</em> a green aqueous-phase hydrothermal method, offering stable colloidal properties and controlled release of therapeutic H₂S and Zn²⁺ under different pH conditions. Upon UV crosslinking, SilMA formed a porous, shear-thinning hydrogel (SF hydrogel) that facilitates <em>in situ</em> application and localized drug delivery. ZnS NPs were loaded into SF hydrogels and the resulting SF/ZnS hydrogel exhibited suitable mechanical strength, swelling and biodegradability for wound healing application. <em>In vitro</em> studies demonstrated the ZnS NPs' potent ROS-scavenging capacity and cytocompatibility, while the SF/ZnS hydrogel effectively restored fibroblasts and endothelial cells' function under oxidative stress and promoted macrophage polarization toward a reparative M2 phenotype. In a streptozotocin-induced diabetic mouse model, SF/ZnS hydrogel significantly accelerated wound closure, enhanced re-epithelialisation and collagen remodelling, and promoted neovascularization, while mitigating chronic inflammation. The SF/ZnS hydrogel developed in this study presents a promising therapeutic platform for chronic diabetic wounds, integrating redox regulation, immunomodulation, and regenerative enhancement within a single injectable system.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214674"},"PeriodicalIF":6.0,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145842855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transformative biomaterials innovations for healthcare: Quantitative insights into translation of labscale research to inventions in global landscape","authors":"Ajoy Mallik ,&nbsp;Bejou Krishhna ,&nbsp;Bikramjit Basu","doi":"10.1016/j.bioadv.2025.214665","DOIUrl":"10.1016/j.bioadv.2025.214665","url":null,"abstract":"<div><div>The expansive domain of Biomaterials Science represents a pivotal axis in the advancement of basic and translational research, bearing significant societal implications for human health worldwide. Within the methodological limitation (2004–2023), a comprehensive scientometric review enabled us to critically explore the growth of research output (70746 publications) and inventions (66434 patents) across various micro-topics, which include hydroxyapatite, hydrogels, protein adsorption, silk fibroin, mesenchymal stem cells, electrospinning, dental implants, Mg-alloys, chitosan, Ti-alloys, additive manufacturing, decellularisation and polyurethane. Intriguingly, the compound annual growth rate (CAGR) of research publications is three times that of patents in the case of Mg-alloys, while comparable CAGR values were recorded for additive manufacturing. Most importantly, this review identifies a notable discrepancy between the number of publications and patents in a specific micro-topic, e.g., naturally derived and decellularized tissue. An emphasis was placed on h-index/g-index metrics as well as comparing multi-country versus single-country publications of the most productive 20 countries, in our eforts to highlight the global influence, visibility and contributions of the top 20 WoS-indexed journals to advance scientific knowledge across disciplines. Despite several decades of research to develop new biomaterials, fewer than 15 biomaterials, either synthetic or naturally derived, have been approved by global regulatory agencies. This gap can be addressed through more invention-driven and industry-focused innovation programs within a strict regulatory framework, as analysed in this review using collaboration network maps and other quantitative metrics related to patents. The policy recommendations, together with the proposed roadmap, call for cohesive international efforts to bridge existing research gaps, foster innovation, and implement strategic policies to ensure the accelerated translation of labscale research to regulatory approved implantable biomaterials and medical devices.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214665"},"PeriodicalIF":6.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic profiling of osteoblasts on hydroxyapatite-coated-metal-surface reveals enhanced osteogenic and angiogenic processes relevant to accelerated bone healing","authors":"Yuki Ogawa ,&nbsp;Kosuke Arita ,&nbsp;Takayuki Nonoyama ,&nbsp;Kano Sato ,&nbsp;Ryota Watanabe ,&nbsp;Liyile Chen ,&nbsp;Tsutomu Endo ,&nbsp;Taiki Tokuhiro ,&nbsp;Hend Alhasan ,&nbsp;Daisuke Takahashi ,&nbsp;Norimasa Iwasaki ,&nbsp;M. Alaa Terkawi","doi":"10.1016/j.bioadv.2025.214672","DOIUrl":"10.1016/j.bioadv.2025.214672","url":null,"abstract":"<div><div>Hydroxyapatite (HA) coating on orthopedic implants is known to promote osteogenesis and improve bone-implant integration, yet its molecular basis remains to be investigated. Here, transcriptomic profiling of osteoblasts on nano-HA (nHA)-coated surfaces revealed increased expression of key osteogenic and angiogenic molecules. These findings provide the first molecular mechanistic insight into how nHA coatings accelerate osteogenesis and bone healing.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214672"},"PeriodicalIF":6.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145842858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterojunction-engineered CNT–MOF hybrid platform for synergistic amplified therapy of bacterial-infected wounds","authors":"Yinuo Li ,&nbsp;Peng Sun ,&nbsp;Wenyi Xu,&nbsp;Huanhuan Li,&nbsp;Hongming Yang,&nbsp;Baolong Zhou","doi":"10.1016/j.bioadv.2025.214669","DOIUrl":"10.1016/j.bioadv.2025.214669","url":null,"abstract":"<div><div>Bacterial wound infections pose a serious clinical threat, often leading to impaired healing and severe complications. To address this challenge, we developed CNT@Por-Cu-MOF, a heterojunction material constructed via in situ growth of Cu(I)–carbon-bonded porphyrin-based metal organic framework (Por-Cu-MOF) as a nano-layer on carbon nanotubes (CNTs). The hierarchical porous structure of the composite enhances therapeutic performance by improving the diffusion of reactive substrates and facilitating the conversion of photonic energy into cytotoxic effects. Under light irradiation, this design enables a self-reinforcing therapeutic cycle that synergistically amplifies antibacterial efficacy through three interconnected mechanisms. Specifically, photothermal conversion elevates local temperature and accelerates enzymatic catalytic kinetics. Hybrid type I/II photodynamic reactions that generate multiple reactive oxygen species (ROS), breaking the hypoxia-induced limitations of conventional phototherapy. Dual enzyme-mimetic catalytic activities, including the peroxidase (POD)- and glutathione peroxidase (GPx)-like behavior that convert endogenous H₂O₂ into •OH while depleting glutathione (GSH), thereby disrupting the redox balance in bacteria. At only 100 μg/mL, CNT@Por-Cu-MOF not only completely eradicates <em>Staphylococcus aureus</em> (<em>S. aureus</em>) and <em>Escherichia coli</em> (<em>E. coli</em>), but effectively removes their biofilms. In a murine wound infection model, the combination of the material, H₂O₂, and laser irradiation significantly accelerated wound healing through integrated photothermal ablation, photodynamic penetration, and catalytic oxidative stress. By leveraging and reprogramming the infected microenvironment, this study introduces a pioneering approach to creating antibacterial platforms with low dosage, broad-spectrum coverage, and hypoxia resistance.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214669"},"PeriodicalIF":6.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of surface chemistry and structure on bacterial adhesion on titanium dioxide materials with extreme wetting","authors":"Ke Wu ,&nbsp;Zhenyu Shen ,&nbsp;Jie Wu ,&nbsp;Zhiwei Chen ,&nbsp;Yun Yang ,&nbsp;Qiaoling Huang","doi":"10.1016/j.bioadv.2025.214673","DOIUrl":"10.1016/j.bioadv.2025.214673","url":null,"abstract":"<div><div>Although it is widely believed that the antibacterial adhesion resistance of superhydrophobic surfaces stems from trapped air layers, the specific contributions of surface microstructure and trapped air layers in preventing bacterial adhesion remain unclear. In this study, four hydrophobic titanium dioxide (TiO₂) materials with different nanostructures were prepared, and ultrasonication was used to effectively remove trapped air, enabling a direct comparison of the hydrophobic materials with variations in surface morphology and trapped air. The results demonstrated that for the superhydrophilic samples, a large number of bacteria adhered to the surfaces, and no significant differences were observed among the various nanostructures. In sharp contrast, all four hydrophobic materials significantly reduced bacterial adhesion, with no significant differences observed among surfaces with different topographies. Millimeter scale, macroscopically visible air bubbles at the solid-liquid interphase greatly suppressed the bacterial adhesion, and the bubbles disappeared or decreased with the elapsed time. In contrast, invisible small bubbles (micrometer- or nanometer-scale) cannot decrease bacterial adhesion compared with the ultrasonicated sample (without trapped air). Therefore, the main reason for the significant reduction in bacterial adhesion on various hydrophobic surfaces is the fluorosilane surface modification. Air at the solid–liquid interface can only suppress the bacterial adhesion when it forms millimeter scale, visible bubbles. This work gives new ideas to the antibacterial application of superhydrophobic materials and is of great significance for the design of biomaterial surfaces with anti-adhesive properties.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"182 ","pages":"Article 214673"},"PeriodicalIF":6.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microenvironment-responsive nanorobots for biomedical applications","authors":"Wenge Lv ,&nbsp;Liangcheng Gu ,&nbsp;Xingyu Lin ,&nbsp;Chun Mao ,&nbsp;Ya Guan ,&nbsp;Mimi Wan","doi":"10.1016/j.bioadv.2025.214666","DOIUrl":"10.1016/j.bioadv.2025.214666","url":null,"abstract":"<div><div>Conventional drug therapies face significant limitations in complex physiological environments, including poor targeting efficiency, passive diffusion mechanisms, and systemic toxicity. Inspired by the immune system, where immune cells are actively navigated by chemotactic gradients to reach infection sites, researchers have developed nanorobots capable of autonomous, microenvironment-responsive drug delivery. These nanorobots convert endogenous biochemical cues (e.g., pH, enzymes, reactive oxygen species) into directed motion and structure or shape changes, enabling deep tissue penetration and lesion-specific drug release. This review categorizes microenvironment-responsive nanorobots into three functional classes—locomotion, degradation, and deformation—based on their response behaviors to pathological signals. We critically analyze their design principles, biomedical applications in different diseases, and translational challenges. By bridging bioinspired strategies with engineered nanorobotics, this work provides a roadmap for next-generation precision therapeutics.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214666"},"PeriodicalIF":6.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The extracellular matrix HA promotes the YAP/hypoxia axis of glioblastoma cells on 3D agar/HA scaffolds","authors":"Nicole Fratini ,&nbsp;Carolina Castillo ,&nbsp;Roberta Grillo ,&nbsp;Stefania D'Amone ,&nbsp;Luca Pacini ,&nbsp;Maddalena Grieco ,&nbsp;Maria Grazia Lolli ,&nbsp;Sara Maria Giannitelli ,&nbsp;Francesco Brasili ,&nbsp;Ornella Ursini ,&nbsp;Claudia Bearzi ,&nbsp;Roberto Rizzi ,&nbsp;Barbara Cortese","doi":"10.1016/j.bioadv.2025.214664","DOIUrl":"10.1016/j.bioadv.2025.214664","url":null,"abstract":"<div><div>The tumour microenvironment of glioblastoma (GBM) as defined by mechanical heterogeneity, hypoxia, and hyaluronic acid (HA)–rich extracellular matrix (ECM), is a highly dynamic milieu which influences tumour progression and therapeutic resistance. Yet, how these cues converge to regulate mechanosensitive pathways in 3D remains poorly understood. Here, we engineered agar-based porous hydrogels functionalized with HA to independently tune stiffness and ECM composition, creating biomimetic 3D niches for GBM cells. The presence of HA coating showed to increase hydrogel stiffness, promote YAP/TAZ nuclear localisation, and elevate total LATS1/2 expression, consistent with Hippo pathway feedback regulation. Over time, however, hypoxic niches emerged that destabilised this feedback, enabling sustained YAP nuclear activity. HA also modulated OCT4 and Sox2 localisation and attenuated HIF-1α nuclear accumulation, indicating that HA also modulates the spatial distribution and nuclear accumulation of HIF-1α. Also, a cooperative regulation through the HA–CD44–CXCR4 axis, showed integrated biochemical and mechanical signals to reinforce YAP/HIF crosstalk. Together, these results reveal a dynamic interplay between ECM stiffness, HA signalling, and hypoxia in shaping YAP/HIF crosstalk and stem-like phenotypes in GBM and establish our hydrogel platform as a powerful tool to dissect and therapeutically exploit these interactions.</div></div>","PeriodicalId":51111,"journal":{"name":"Materials Science & Engineering C-Materials for Biological Applications","volume":"181 ","pages":"Article 214664"},"PeriodicalIF":6.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}