Biomaterials最新文献

{"title":"NIR-activated nanodisguisers for targeted bactericidal action and enhanced electron transfer in periodontitis treatment","authors":"Manlin Qi ,&nbsp;Qihang Ding ,&nbsp;Yujia Shi ,&nbsp;Kun Wang ,&nbsp;Jia Liu ,&nbsp;Jing Zhou ,&nbsp;Wei Zhang ,&nbsp;Chengyu Liu ,&nbsp;Shuang Liang ,&nbsp;Biao Dong ,&nbsp;Jong Seung Kim ,&nbsp;Lin Wang","doi":"10.1016/j.biomaterials.2025.123487","DOIUrl":"10.1016/j.biomaterials.2025.123487","url":null,"abstract":"<div><div>Antibacterial treatment for periodontitis faces significant challenges due to the lack of selective bactericidal therapies. In this study, we developed multifunctional nanospheres encapsulated with <em>Fusobacterium nucleatum</em>-derived outer membrane vesicles (OMVs) to target periodontal pathogens specifically. These OMVs act as a \"camouflage,\" allowing the nanospheres to infiltrate bacterial environments undetected, adhere to pathogen surfaces, and maximize therapeutic effects. Direct contact between nanospheres and bacteria accelerates electron transfer, and nanospheres trigger a proliferation of endogenous reactive oxygen species (ROS), leading to oxidative stress and bacterial death. Transcriptomic analysis confirmed that the nanospheres accelerated electron transfer activity and disrupted deoxyribonucleic acid (DNA) repair mechanisms and thiamine metabolism while enhancing bacterial respiration. Though supported by dual photodynamic and photothermal therapies under near-infrared light, the primary mechanism of action focuses on electron transfer and metabolic disruption. In vitro and <em>in vivo</em> experiments demonstrated the nanospheres’ potent biofilm eradication and periodontitis treatment efficacy, offering a promising new approach for selective bacterial targeting. This strategy targets pathogens effectively and preserves the beneficial microbiota, providing an innovative solution for treating periodontitis and other biofilm-related infections.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123487"},"PeriodicalIF":12.8,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrode stimulation parameter modifications elicit differential glial cell responses in vitro over a short 4-h timecourse","authors":"Christopher T. Tsui ,&nbsp;Soroush Mirkiani ,&nbsp;David A. Roszko ,&nbsp;Matthew J. Birtle ,&nbsp;Anna E. DeCorby ,&nbsp;Matthew A. Churchward ,&nbsp;Vivian K. Mushahwar ,&nbsp;Kathryn G. Todd","doi":"10.1016/j.biomaterials.2025.123478","DOIUrl":"10.1016/j.biomaterials.2025.123478","url":null,"abstract":"<div><div>A cell culture model to assess glial cell responses to electrically stimulating electrodes in real-time was developed. Our previous work measured glial cell responses to stimulation paradigms and highlighted the importance of electrical stimulation considerations when designing a biocompatible neural interfacing device. The formation of voids around stimulating platinum-iridium electrodes also prompted an investigation into the fate of cells that would have once populated that area. Live-imaging experiments involving EGFP-positive microglia from heterozygous CX3CR-1^+/EGFP mice were designed. Live-imaging animations over 4 h showed necrotic microglial cell death around stimulating electrodes. The degree to which this was occurring was further analyzed by electrically stimulating mixed glia and modifying parameters such as stimulation amplitude (0.1–0.4 mA), waveform shape (rectangular/sinusoidal/ramped), and frequency (25–55 Hz). The different stimulation parameters had differential effects on glial cell biomarker signal outputs (cell density, fluorescence intensity, area coverage). Scanning electron microscopy and energy-dispersive x-ray spectroscopy of the electrode surfaces post-stimulation did not reveal any significant damage or changes to surface elemental composition. Finally, electrochemical testing of the proposed <em>in vitro</em> setup revealed influences of different components of the mixed glial cell cultures towards the electrochemical performance of the electrodes in terms of cathodic charge storage capacity, impedance, phase angle, and voltage transient excursions. The results highlight the impact that electrical stimulation parameters have on glial cell fate at the electrode-cell culture interface, and provide data towards refinement of stimulation paradigms used in electrical neuromodulation applications.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123478"},"PeriodicalIF":12.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thiol-ene photoclick hydrogels reinforced with poly(protocatechualdehyde)-coated gallium doped bioactive glass nanoparticles for scarless healing of infected wound","authors":"Xinyi Jian ,&nbsp;Dun Liu ,&nbsp;Xuexue Liu ,&nbsp;Xingping Zhao ,&nbsp;Yongjie Zhu ,&nbsp;Sanqiang Xia ,&nbsp;Enuo Peng ,&nbsp;Mengran Zhao ,&nbsp;Jie Yi ,&nbsp;Guohua Jiang ,&nbsp;Dabao Xu ,&nbsp;Kui Cheng ,&nbsp;Wenjian Weng ,&nbsp;Zezhang Zhu ,&nbsp;Benlong Shi ,&nbsp;Bolin Tang","doi":"10.1016/j.biomaterials.2025.123469","DOIUrl":"10.1016/j.biomaterials.2025.123469","url":null,"abstract":"<div><div>Complex pathological microenvironment mainly characterized by excessive inflammation, reactive oxygen species (ROS) production, drug-resistant bacterial infection makes wound rapid scarless healing still a major clinical challenge. Inspired by skin composed principally of collagen and mucopolysaccharides, an injectable nanocomposite hydrogel with immunoregulation, antioxidant and antibacterial activity based on allyl glycidyl ether grafted gelatin (Gel-AGE), cysteamine grafted hyaluronic acid (HA-CSA) and poly(protocatechualdehyde)-coated gallium doped bioactive glass (PPA@GaBG) nanoparticles, was designed for treatment of infected wound. The PPA@GaBG/Gel-AGE/HA-CSA (PGBGH) hydrogel can be rapidly formed via thiol-ene photo-click chemistry between Gel-AGE and HA-CSA. In PGBGH hydrogel, the presence of core-shell PPA@GaBG significantly enhanced the antioxidant ability of hydrogels and M2 polarization of macrophages, as well as improving mechanical and tissue adhesive properties of the hydrogels via the formation of Schiff base bonds between PPA and gelatin/skin tissue. Moreover, the PPA shell effectively inhibited the ion burst release of Ga³⁺ observed in GaBG/GH hydrogels, which improved the biocompatibility of the PGBGH hydrogel while maintaining excellent antibacterial activity. As a result of multiple functions of the PPA@GaBG, the PGBGH hydrogel promoted angiogenesis, granulation tissue formation and re-epithelialization with improved deposition ratio of collagen III/I, which achieved the rapid scarless healing of infected wound.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123469"},"PeriodicalIF":12.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metal-phenolic networks assisted construction of multi-layered endothelium-mimetic polyelectrolyte coating with nitric oxide generation and glycocalyx functionalization","authors":"Chong Chen ,&nbsp;Chunle Zhang ,&nbsp;Tao Yu ,&nbsp;Yumei Qin ,&nbsp;Yu Chen ,&nbsp;Yan Xiong ,&nbsp;Rifang Luo ,&nbsp;Yunbing Wang ,&nbsp;Ping Fu","doi":"10.1016/j.biomaterials.2025.123486","DOIUrl":"10.1016/j.biomaterials.2025.123486","url":null,"abstract":"<div><div>During cardiovascular-stent endothelialization, application of an endothelium-mimetic coating is desirable to establish a conducive microenvironment that promotes endothelialization, thereby reducing the risks of in-stent thrombosis and restenosis. In this study, we construct an endothelium-mimetic coating on vascular stents assisted by metal-phenolic networks (MPNs). The functional components are integrated through a layer-by-layer self-assembly technique with positively charged polyethyleneimine, negatively charged hyaluronic acid (HA), and MPNs composed of epigallocatechin gallate and Cu as a sandwiched assisting interlayer. Vasoactive nitric oxide (NO) released by Cu catalysis along with the glycocalyx major component HA modification on the surface, endow vascular stents with protective functionalities similar to that of natural endothelial cells. The presence of cation–anion electrolytes and polyphenols enhances the loading, stability, and uniformity of the coating through various interactions such as electrostatic adsorption, hydrogen bonding, π–π stacking, and covalent crosslinking of phenol–aldehyde–amine. Systematic in-vitro and in-vivo studies demonstrate that this coating significantly reduces platelet adhesion and activation and thrombus formation, selectively promotes endothelial cells proliferation and regulates the behaviour of smooth muscle cells, and mitigates inflammatory responses by the synergistic effects of NO catalytic release and glycocalyx functionalization. In-vivo stent implantation experiment reveals that, compared to bare stents, this coating accelerates stent endothelialization and inhibits intimal hyperplasia of vessels. Three months after implantation, the lumen loss rate of the coated stent is only one-third of that of the bare stent. Overall, the MPNs-assisted construction of multi-layered endothelium-mimetic polyelectrolyte coatings with a dual-modality strategy integrating contact therapy via glycocalyx functionalization and gas therapy via NO generation provides innovative insights for the development of next-generation stents. The proposed method can serve as a universal surface-modification strategy to enhance the biocompatibility of implantable cardiovascular devices.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123486"},"PeriodicalIF":12.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omic spatially resolved analysis of the neuroinflammatory response to intracortical microelectrode arrays","authors":"Lindsey N. Druschel ,&nbsp;Sydney S. Song ,&nbsp;Niveda M. Kasthuri ,&nbsp;Jaime J. Wang ,&nbsp;Jacob H. Conard ,&nbsp;E. Ricky Chan ,&nbsp;Allison Hess-Dunning ,&nbsp;Jeffrey R. Capadona","doi":"10.1016/j.biomaterials.2025.123477","DOIUrl":"10.1016/j.biomaterials.2025.123477","url":null,"abstract":"<div><div>Intracortical microelectrode arrays (MEAs) are devices implanted into the brain's cortex with the ability to record or stimulate neuronal activity. Unfortunately, MEAs tend to fail over chronic time points, limiting their clinical utility. Chronic failure has largely been attributed to the brain's neuroinflammatory response. Until recently, most of what was understood about the neuroinflammatory response to MEAs was learned through immunohistochemical analysis of small numbers of proteins. More recently, gene expression studies have sequenced thousands of mRNA molecules that contribute to neuroinflammation, but few studies have performed large-scale proteomic analyses. To expand the knowledge of molecular mechanisms involved, we have previously investigated the activity of 62 proteins within 180 μm of the MEA implant site using a spatial proteomic platform. In the present study, we are the first to apply large-scale genomics and proteomics to MEAs, as we evaluate changes in both the whole protein-encoding mouse transcriptome and our 62-protein proteomic panel. We further examine the spatial distribution of the neuroinflammatory response within three distinct domains adjacent to the MEA: 0–90 μm, 90–180 μm, and 180–270 μm from the implant site. Our analysis directly compares the gene and protein expression and highlights the need for segmentation based on proximal distance from the implant site. We also identify key pathways associated with immune cell activation, neurodegeneration, and metabolism that likely contribute to MEA failure and could be targeted to improve MEA performance in future studies.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123477"},"PeriodicalIF":12.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering pancreatic islet-loaded microfibers via pneumatically-controlled microfluidic spinning for the assembly of a microphysiological system","authors":"Jingyan Shi ,&nbsp;Jianing Li ,&nbsp;Jingyun Ma ,&nbsp;Xiaoling Yang ,&nbsp;Chang Xue ,&nbsp;Yuan Zhang ,&nbsp;Xinghua Gao","doi":"10.1016/j.biomaterials.2025.123480","DOIUrl":"10.1016/j.biomaterials.2025.123480","url":null,"abstract":"<div><div>Microphysiological systems, including organ-on-a-chip systems, can achieve <em>in vitro</em> biomimicry of tissues and organs using microfluidic three-dimensional cell culture devices. These technologies can compensate for the shortcomings of animal models in basic disease research, and can even replace them in some cases. For example, they have demonstrated significant advantages and potential in the evaluation and screening of drugs for diabetes. In this study, we developed an islet microphysiological system based on a fibrous material and microfluidic spinning. This system includes pancreatic islet-loaded microfibers prepared using controllable pneumatic valves combined with microfluidic spinning technology and a microfluidic system comprising microfibers assembled with vascular endothelial cells. The results showed that the prepared microfibers loaded a large number of monodisperse pancreatic islet clusters with good cell activity and function. Microfibers were assembled with vascular endothelial cells in a microfluidic system, providing a 3D environment that mimicked natural blood vessels and supported high-throughput cell loading. Microfibers are vascularized by endothelial cells that grow on their surfaces. The microfluidic system simulated capillary blood flow and nutrient exchange, thereby enhancing the physiological relevance of the model. We evaluated the diabetes treatment drug Glucagon-like peptide-1 (GLP-1) using this system. Immunofluorescence staining, RT-qPCR, and ELISA confirmed the glucose-lowering and cardiovascular protective effects of GLP-1. This islet microphysiological system provides a novel platform for studying diabetes, screening new drugs, and promoting personalized medicine. The ability of this system to simulate physiological conditions through the synergy of biophysical and biochemical factors makes it a powerful tool for biomedical research.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123480"},"PeriodicalIF":12.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Osteogenic and antibacterial enhancement by alloying design and microstructural modification of additively manufactured biodegradable metals","authors":"Yijie Liang ,&nbsp;Jiabao Dai ,&nbsp;Zhenbao Zhang ,&nbsp;Aobo Liu ,&nbsp;Jing Xu ,&nbsp;Haoning Tang ,&nbsp;Yuhan Qi ,&nbsp;Manxi Li ,&nbsp;Haixia Li ,&nbsp;Jing Wang ,&nbsp;Yantao Zhao ,&nbsp;Peng Wen ,&nbsp;Yanfeng Li","doi":"10.1016/j.biomaterials.2025.123481","DOIUrl":"10.1016/j.biomaterials.2025.123481","url":null,"abstract":"<div><div>Additively Manufactured metallic implants face a critical challenge in simultaneously promoting osteogenesis and preventing infection, two competing requirements in complex orthopedic applications such as implant-associated infections. This study presents a novel strategy combining Cu alloying and heat treatment for biodegradable zinc-based implants fabricated by laser powder bed fusion (L-PBF), in order to address infected bone repair. After alloying, the as-built Zn-2Cu implants showed limited enhancement compared to pure Zn due to the microstructure dominated by solid solution. Subsequent heat treatment at 350 °C for 3 h induced CuZn₅ precipitation and accelerated galvanic corrosion, remarkably improving strength and biodegradation. The resulting HT/Zn-2Cu alloy achieved a high yield strength of 203 MPa through synergistic strengthening mechanisms. More significantly, the co-released Zn²⁺ and Cu²⁺ at favorable concentrations demonstrated dual functionalities according to comprehensive <em>in vitro</em> and <em>in vivo</em> tests. It enhanced osteogenic activity via stimulated osteoblast proliferation, differentiation, and upregulation of osteogenesis-related genes, and introduced potent antibacterial effects through biofilm disruption and bacterial growth inhibition, revealed by transcriptomic analysis. Such findings establish a new paradigm for designing biodegradable implants that concurrently address bone regeneration and infection prevention in clinical applications.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123481"},"PeriodicalIF":12.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD38-targeted antibody-polymer drug conjugates for enhanced treatment of multiple myeloma","authors":"Jiahui Li ,&nbsp;Shannuo Li ,&nbsp;Hasan Al Faruque ,&nbsp;Jindřich Kopeček ,&nbsp;Douglas W. Sborov ,&nbsp;Jiyuan Yang","doi":"10.1016/j.biomaterials.2025.123464","DOIUrl":"10.1016/j.biomaterials.2025.123464","url":null,"abstract":"<div><div>Multiple myeloma (MM) remains a formidable disease, especially in relapsed or refractory cases when there are limited treatment options. In this study, we introduce two polymer-antibody drug conjugates (pADCs), ISA-P-EPI (U6244-021) and DARA-P-EPI (U6244-031), which contain semitelechelic <em>N</em>-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-epirubicin (EPI) conjugate attached to CD38-targeting antibodies Isatuximab (ISA) and Daratumumab (DARA). These pADCs enhance therapeutic efficacy by combining the specificity of ISA and DARA with the cytotoxic potency of EPI while preserving antibody function. The EPI is linked to the HPMA polymer backbone via a tetrapeptide spacer cleavable by lysosomal enzymes, enabling drug release upon endocytosis within tumor cells. This design achieves a higher drug-to-antibody ratio than conventional ADCs for safer delivery of drug payload.</div><div>In vitro studies demonstrate efficient binding, internalization, and cytotoxic efficacy of these pADCs in MM cell lines. Mechanistic investigations revealed significant therapeutic effects, including cell cycle arrest, immunogenic cell death, and preserved antibody-dependent cellular cytotoxicity (ADCC). In addition, pADCs were effective in 5 out of 8 primary samples, with their efficacy closely correlating with CD38 surface expression levels. To enhance therapeutic outcomes, we employed panobinostat to upregulate CD38 expression, which further improved pADC efficacy. In a preclinical NRG mouse model inoculated with MM.1S-luc cells, pADC treatment significantly delayed tumor progression and prolonged survival, with all treated mice remaining alive at the 100-day endpoint.</div><div>These findings underscore the potential of CD38-targeted pADCs as a novel approach to combining chemotherapy with immunotherapy for MM treatment, warranting further investigation into their optimization and clinical application.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123464"},"PeriodicalIF":12.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the senescent surfaceome through DPP4 antibody-functionalized nanoparticles. An application to cancer therapy","authors":"Blanca Escriche-Navarro ,&nbsp;Eva Garrido ,&nbsp;Andrea Escudero ,&nbsp;Isabel Montoya-Méndez ,&nbsp;Félix Sancenón ,&nbsp;Alba García-Fernández ,&nbsp;Ramón Martínez-Máñez","doi":"10.1016/j.biomaterials.2025.123461","DOIUrl":"10.1016/j.biomaterials.2025.123461","url":null,"abstract":"<div><div>Due to the heterogeneity of the senescent phenotype and the lack of a universal biomarker of senescence, the targeting of senescent cells is still an unresolved challenge, and the elimination of senescent cells using specific drugs (senolytics) is still limited in clinical use due to the off-target effects and associated toxicities of current therapeutic strategies. In this study, the induction of senescence in human melanoma cells by palbociclib is found to lead to a senescent phenotype characterized by overexpression of the membrane protein dipeptidyl peptidase 4 (DPP4), previously identified only in ageing contexts. Based on this discovery, a nanoparticle targeting DPP4 overexpression in the senescent surfaceome is designed, synthesized, and characterized to target senescent cancer cells. The nanoparticle based on mesoporous silica is loaded with the senolytic navitoclax, coated with disulfide-containing poly(ethylene glycol) to generate a redox-sensitive gatekeeper (S–S-PEG), and functionalized with an antibody against the DPP4 protein. The ability of the nanoparticles to effectively detect and eliminate senescent cells was confirmed <em>in vitro</em> and <em>in vivo</em> using a mouse model of palbociclib-induced senescent in melanoma. The DPP4-targeted nanoparticle effectively reduces tumor growth and selectively removes senescent cells. Taken together, this study highlights the potential of surfaceome-targeted nanoparticles, as a clinically relevant strategy for improving senolytic therapies.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123461"},"PeriodicalIF":12.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tunable biomechanical niches regulate hepatic differentiation of mesenchymal stem cells for acute liver failure therapy","authors":"Tiantian Xue ,&nbsp;Jiabin Zhang ,&nbsp;Fenfang Li ,&nbsp;Guipan Chen ,&nbsp;Ke Yi ,&nbsp;Xiaodie Chen ,&nbsp;Yixin Zhang ,&nbsp;Yanteng Xu ,&nbsp;Haixia Wang ,&nbsp;Enguo Ju ,&nbsp;Xi Xie ,&nbsp;Mingqiang Li ,&nbsp;Yu Tao","doi":"10.1016/j.biomaterials.2025.123458","DOIUrl":"10.1016/j.biomaterials.2025.123458","url":null,"abstract":"<div><div>Acute liver failure (ALF) is a critical disease characterized by hepatocyte necrosis and liver dysfunction. Currently, effective treatments such as liver and hepatocyte transplantation are hindered by donor shortages. Consequently, hepatocyte-like cells (HLCs) derived from human adipose-derived mesenchymal stem cells (hADSCs) present substantial therapeutic potential as alternative cells. Establishing a supportive niche is conducive to regulating the differentiation of hADSCs into HLCs with the necessary metabolic and therapeutic functions. In this study, we develop a hydrogel-based synthetic niche composed of decellularized extracellular matrix (dECM) and oxidized dextran (ODex). These hydrogels, with tunable viscoelasticity and stiffness, regulate hepatic differentiation through Yes-associated protein (YAP) mechanotransduction. Specifically, a combination of faster stress relaxation rate and lower stiffness approximating that of mouse liver fosters the hepatic differentiation of hADSCs. Additionally, this niche also promotes HLC paracrine functions in pro-angiogenesis, anti-oxidative stress, and anti-inflammation. In vivo experiments reveal that hydrogel-based biomechanical niches-regulated HLCs demonstrate satisfactory therapeutic effects in mice with CCl₄-induced ALF. Overall, this hydrogel-based stem cell niche, which mimics the characteristics of the native liver, with optimized differentiation efficiency and therapeutic potential, offers a promising approach for leveraging biomaterials in liver tissue engineering.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"324 ","pages":"Article 123458"},"PeriodicalIF":12.8,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}