Biomaterials最新文献

{"title":"Molybdenum nanodots act as antioxidants for photothermal therapy osteoarthritis","authors":"Guang Shi ,&nbsp;Shenghui Lan ,&nbsp;Qi Zhang ,&nbsp;Junwu Wang ,&nbsp;Feihong Shu ,&nbsp;Zhuowen Hao ,&nbsp;Tianhong Chen ,&nbsp;Mengyue Zhu ,&nbsp;Renxin Chen ,&nbsp;Jiayao Chen ,&nbsp;Zijian Wu ,&nbsp;Bo Wu ,&nbsp;Zhenwei Zou ,&nbsp;Jingfeng Li","doi":"10.1016/j.biomaterials.2024.122909","DOIUrl":"10.1016/j.biomaterials.2024.122909","url":null,"abstract":"<div><div>Osteoarthritis (OA) manifests as the degradation of cartilage and remodeling of subchondral bone. Restoring homeostasis within the joint is imperative for alleviating OA symptoms. Current interventions primarily target singular aspects, such as anti-aging, inflammation inhibition, free radical scavenging, and regeneration of cartilage and subchondral bone. Herein, we developed molybdenum nanodots (MNDs) as bionic photothermal nanomaterials to mimic the antioxidant synthase to concurrently protected cartilage and facilitate subchondral bone regeneration. With near-infrared (NIR) irradiation, MNDs effectively eliminate reactive oxygen and nitrogen species (ROS/RNS) from OA chondrocytes, thereby reversed mitochondrial dysfunction, mitigating chondrocyte senescence, and simultaneously suppresses inflammation, hence preserving the inherent homeostasis between cartilage matrix synthesis and degradation while circumventing safety concerns. RNA sequencing of OA chondrocytes treated with MNDs-NIR revealed the reinstatement of chondrocyte functionality, activation of antioxidant enzymes, anti-aging properties, and regulation of inflammation. NIR irradiation induces thermogenesis and synergistically promotes subchondral bone regeneration via MNDs, as validated through histological assessments and microcomputed tomography (Micro-CT) scans. MNDs-NIR effectively attenuate cellular senescence and inhibit inflammation in vivo, while also remodeling mitochondrial dynamics by upregulating fusion proteins and inhibiting fission proteins, thereby regulating the oxidative stress microenvironment. Additionally, MNDs-NIR exhibited remarkable therapeutic effects in alleviating articular cartilage degeneration in an OA mouse model, evidenced by a 1.67-fold reduction in subchondral bone plate thickness, an 88.57 % decrease in OARSI score, a 5.52-fold reduction in MMP13 expression, and a 6.80-fold increase in Col II expression. This novel disease-modifying approach for OA utilizing MNDs-NIR offers insight and a paradigm for improving mitochondrial dysfunction by regulating the accumulation of mitochondrial ROS and ultimately alleviating cellular senescence. Moreover, the dual-pronged therapeutic approach of MNDs-NIR, which addresses both cartilage erosion and subchondral bone lesions in OA, represents a highly promising strategy for managing OA.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122909"},"PeriodicalIF":12.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542449","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":"Electrically-driven drug delivery into deep cutaneous tissue by conductive microneedles for fungal infection eradication and protective immunity","authors":"Sumanta Ghosh ,&nbsp;Mengjia Zheng ,&nbsp;Jiahui He ,&nbsp;Yefeng Wu ,&nbsp;Yaming Zhang ,&nbsp;Weiping Wang ,&nbsp;Jie Shen ,&nbsp;Kelvin W.K. Yeung ,&nbsp;Prasanna Neelakantan ,&nbsp;Chenjie Xu ,&nbsp;Wei Qiao","doi":"10.1016/j.biomaterials.2024.122908","DOIUrl":"10.1016/j.biomaterials.2024.122908","url":null,"abstract":"<div><div>Fungal infections affect over 13 million people worldwide and are responsible for 1.5 million deaths annually. Some deep cutaneous fungal infections may extend the dermal barriers to cause systemic infection, resulting in substantial morbidity and mortality. However, the management of deep cutaneous fungal infection is challenging and yet overlooked by traditional treatments, which only offer limited drug availability within deep tissue. In this study, we have developed an electrically stimulated microneedle patch to deliver miconazole into the subcutaneous layer. We tested its antifungal efficacy using <em>in vitro</em> and <em>ex vivo</em> models that mimic fungal infection. Moreover, we confirmed its anti-fungal and wound-healing effects in a murine subcutaneous fungal infection model. Furthermore, our findings also showed that the combination of miconazole and applied current synergistically stimulated the nociceptive sensory nerves, thereby activating protective cutaneous immunity mediated by dermal dendritic and γδ-T cells. Collectively, this study provides a new strategy for minimally invasive delivery of therapeutic agents and the modulation of the neuro-immune axis in deep tissue.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122908"},"PeriodicalIF":12.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491859","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":"Biologically logic-gated Trojan-horse strategy for personalized triple-negative breast cancer precise therapy by selective ferroptosis and STING pathway provoking","authors":"Shuai Guo ,&nbsp;Tianwang Guan ,&nbsp;Yushen Ke ,&nbsp;Yuping Lin,&nbsp;Rundong Tai,&nbsp;Jujian Ye,&nbsp;Zhilin Deng,&nbsp;Shaohui Deng,&nbsp;Caiwen Ou","doi":"10.1016/j.biomaterials.2024.122905","DOIUrl":"10.1016/j.biomaterials.2024.122905","url":null,"abstract":"<div><div>Amidst the therapeutic quandaries associated with triple-negative breast cancer (TNBC), an aggressive malignancy distinguished by its immune resistance and limited treatment avenues, the urgent need for innovative solutions is underscored. To conquer the dilemma, we present a groundbreaking approach that ingeniously employs DNA-fragments-containing exosomes (DNA-Exo) and the concept of “biological logic-gates” to achieve precise homing and controlled selective activation of ferroptosis and stimulator interferon genes (STING) pathways. Leveraging insights from our previous research, a nano-Trojan-horse, Fe⁰@HMON@DNA-Exo, is engineered <em>via in situ</em> Fe⁰ synthesis within the glutathione (GSH)-responsiveness degradable hollow mesoporous organosilica nanoparticles (HMON) and subsequently enveloped in DNA-Exo derived from 7-ethyl-10-hydroxycamptothecin (SN38)-treated 4T1 cells. Emphasizing the precision of our approach, the DNA-Exo ensures specific ‘homing’ to TNBC cells, rendering a targeted delivery mechanism. Concurrently, the concept of “biological logic-gates” is employed to dictate a meticulous and selective activation of STING in antigen-presenting cells (APCs) under OR logic-gating with robust immune response and Fe⁰-based ferroptosis in TNBC cells under AND logic-gating with reactive oxygen species (ROS) storm generation. In essence, our strategy exhibits great potential in transforming the “immunologically cold” nature of TNBC, enabling precise control over cellular responses, illuminating a promising therapeutic paradigm that is comprehensive and productive in pursuing precision oncology and paving the way for personalized TNBC therapies.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122905"},"PeriodicalIF":12.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538496","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":"Genetically modified extracellular vesicles loaded with activated gasdermin D potentially inhibit prostate-specific membrane antigen-positive prostate carcinoma growth and enhance immunotherapy","authors":"Ke Gao ,&nbsp;Wenjin Xi ,&nbsp;Jianxin Ni ,&nbsp;Jun Jiang ,&nbsp;Yonghua Lei ,&nbsp;Lin Li ,&nbsp;Jie Chu ,&nbsp;Ruixiao Li ,&nbsp;Yongpan An ,&nbsp;Yanan Ouyang ,&nbsp;Ruiping Su ,&nbsp;Rui Zhang ,&nbsp;Guojun Wu","doi":"10.1016/j.biomaterials.2024.122894","DOIUrl":"10.1016/j.biomaterials.2024.122894","url":null,"abstract":"<div><div>Prostate cancer (PCa) is associated with poor immunogenicity and lymphocytic infiltration, and immunotherapy effective against PCa remains unavailable. Pyroptosis, a novel immunotherapeutic modality for cancer, promotes systemic immune responses leading to immunogenic cell death in solid tumors. This paper describes the preparation and analysis of PSMA_scFv-EV^N-GSDMD; this genetically engineered recombinant extracellular vesicle (EV) expresses a single-chain variable antibody fragment (scFv) with high affinity for prostate-specific membrane antigen (PSMA) on their surfaces and is loaded with the N-terminal domain of gasdermin D (GSDMD). Both in vitro and in vivo, PSMA_scFv-EV^N-GSDMD effectively targeted PSMA-positive PCa cells and induced pyroptosis through the carrier properties of EVs and the specificity of PSMA_scFv. In the 22RV1 and PSMA-transfected RM-1-inoculated PCa mouse models, PSMA_scFv-EV^N-GSDMD efficiently inhibited tumor growth and promoted tumor immune responses. In conclusion, PSMA_scFv-EV^N-GSDMD can convert the immunosuppressive “cold” tumor microenvironment of PCa into an immunogenic “hot” tumor microenvironment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122894"},"PeriodicalIF":12.8,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix stiffening from collagen fibril density and alignment modulates YAP-mediated T-cell immune suppression","authors":"Jiranuwat Sapudom ,&nbsp;Aseel Alatoom ,&nbsp;Paul Sean Tipay ,&nbsp;Jeremy CM. Teo","doi":"10.1016/j.biomaterials.2024.122900","DOIUrl":"10.1016/j.biomaterials.2024.122900","url":null,"abstract":"<div><div>T-cells are essential components of the immune system, adapting their behavior in response to the mechanical environments they encounter within the body. In pathological conditions like cancer, the extracellular matrix (ECM) often becomes stiffer due to increased density and alignment of collagen fibrils, which can have a significant impact on T-cell function. In this study, we explored how these ECM properties—density and fibrillar alignment—affect T-cell behavior using three-dimensional (3D) collagen matrices that mimic these conditions. Our results show that increased matrix stiffness, whether due to higher density or alignment, significantly suppresses T-cell activation, reduces cytokine production, and limits proliferation, largely through enhanced YAP signaling. Individually, matrix alignment appears to lower actin levels in activated T-cells and changes migration behavior in both resting and activated T-cells, an effect not observed in matrices with randomly oriented fibrils. Notably, inhibiting YAP signaling was able to restore T-cell activation and improve immune responses, suggesting a potential strategy to boost the effectiveness of immunotherapy in stiff ECM environments. Overall, this study provides new insights into how ECM characteristics influence T-cell function, offering potential avenues for overcoming ECM-induced immunosuppression in diseases such as cancer.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122900"},"PeriodicalIF":12.8,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491868","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":"3D printing incorporating gold nanozymes with mesenchymal stem cell-derived hepatic spheroids for acute liver failure treatment","authors":"Yuanyuan Jin ,&nbsp;Jiabin Zhang ,&nbsp;Xiaodie Chen ,&nbsp;Fenfang Li ,&nbsp;Tiantian Xue ,&nbsp;Ke Yi ,&nbsp;Yanteng Xu ,&nbsp;Haixia Wang ,&nbsp;Yeh-Hsing Lao ,&nbsp;Hon Fai Chan ,&nbsp;Dan Shao ,&nbsp;Mingqiang Li ,&nbsp;Yu Tao","doi":"10.1016/j.biomaterials.2024.122895","DOIUrl":"10.1016/j.biomaterials.2024.122895","url":null,"abstract":"<div><div>Acute liver failure (ALF) is a highly fatal disease, necessitating the advancement and optimization of alternative therapeutic strategies to benefit patients awaiting liver transplantation. In this study, we innovatively established the antioxidant nanozyme-hepatocyte-like cells (HLCs) microtissue sheets (HS/N–Au@composite) for ALF therapy. We first prepared a 3D-printed hyaluronic acid/gelatin/sodium alginate scaffold with N-acetylcysteine (NAC)-capped gold nanoclusters (NAC-Au NCs), forming the N–Au@hydrogel. For the encapsulation of HLC spheroids, we used a biocompatible hybrid hydrogel composed of decellularized extracellular matrix (dECM), thrombin, and fibrinogen, resulting in the HS@dECM hydrogel. Utilizing 3D printing technology, we integrated the N–Au@hydrogel with the HS@dECM hydrogel to create the HS/N–Au@composite for in situ transplantation to treat ALF. Our results demonstrated that NAC-Au NCs effectively mitigated reactive oxygen species (ROS)-induced liver necrosis in ALF. Additionally, the N–Au@hydrogel provided mechanical support, ensuring the proper landing and effective functioning of the transplanted HLC spheroids. The HS/N–Au@composite synergistically decreased serum transaminase levels, reduced the accumulation of pro-inflammatory cytokines, accelerated liver function recovery, and promoted liver regeneration in ALF treatment. This combination of HLC spheroids and NAC-Au NCs nanozymes via 3D-printed composite scaffolds represents a promising strategy for enhancing hepatocyte transplantation and advancing stem cell regenerative medicine in ALF therapy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122895"},"PeriodicalIF":12.8,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491865","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":"Anaerobic bacterial metabolism responsive microspheres for bacterial embolization cancer therapy","authors":"Hyunjun Choi ,&nbsp;Bongseo Choi ,&nbsp;Dong-Hyun Kim","doi":"10.1016/j.biomaterials.2024.122902","DOIUrl":"10.1016/j.biomaterials.2024.122902","url":null,"abstract":"<div><div>Anaerobic bacteriolytic cancer therapy, whether delivered locally or systemically, frequently encounters challenges related to limited colonization within hypoxic pockets of central tumors and activation of innate immunity. Herein we have developed trans-arterial bacteria embolization therapy using bacterial embolic microspheres. <em>C. novyi</em>-NT spores loaded calcium alginate embolic microspheres demonstrated <em>C. novyi</em>-NT metabolites-mediated microsphere degradation, releasing vegetative <em>C. novyi</em>-NT bacterial in hypoxic condition. Transcatheter directed bacterial microsphere embolization therapy occludes tumor feeding vessels with infused bacterial embolic microspheres and enhances tumoral hypoxia. Notably, anaerobic bacterial metabolism responsive microsphere-bacterial embolization therapy achieved a complete tumor response with enhanced tumor-specific bacterial delivery and colonization, resulting in cancer cell killing across the entire tumor. <em>In vivo</em> tumor response and immunological profiling revealed that bacterial embolization uniquely enhances anti-cancer response, effectively engaging direct anaerobic bacterial oncolysis and adaptive and innate immune responses in a cooperative manner.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122902"},"PeriodicalIF":12.8,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491858","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":"Engineered bacterium-metal-organic framework biohybrids for boosting radiotherapy with multiple effects","authors":"Jia-Wei Wang ,&nbsp;Ping Ji ,&nbsp;Jin-Yue Zeng ,&nbsp;Jun-Long Liang ,&nbsp;Qian Cheng ,&nbsp;Miao-Deng Liu ,&nbsp;Wei-Hai Chen ,&nbsp;Xian-Zheng Zhang","doi":"10.1016/j.biomaterials.2024.122901","DOIUrl":"10.1016/j.biomaterials.2024.122901","url":null,"abstract":"<div><div>Hypoxia and lactate-overexpressed tumor microenvironment always lead to poor therapeutic effect of radiotherapy. Here, platinum nanoparticles-embellished hafnium metal-organic framework (Hf-MOF-Pt NPs) were elaborately integrated with <em>Shewanella oneidensis</em> MR-1 (SO) to construct an engineered biohybrid platform (SO@Hf-MOF-Pt) for enhancing radiotherapy. Benefiting from the tumor-targeting and metabolic respiration characteristics of SO, SO@Hf-MOF-Pt could enrich in tumor sites and continuously metabolize the overexpressed lactate, which specifically downregulated the expression of hypoxia-inducible factor (HIF-1α), thereby relieving the radiosuppressive tumor microenvironment to some extent. Moreover, SO@Hf-MOF-Pt would react with tumor-overexpressed hydrogen peroxide (H₂O₂) to generate oxygen (O₂) and further inhibit the expression of HIF-1α, resulting in the downregulation of lactate dehydrogenase (LDHA) and subsequently reducing the lactate production. Under these multiple cascaded effects, the radiosuppressive tumor microenvironment was significantly reshaped, thus potentiating the radiosentization of SO@Hf-MOF-Pt and remarkably amplifying the therapeutic outcomes of radiotherapy. The designed biohybrid SO@Hf-MOF-Pt represented promising prospects in sensitizing radiotherapy via bacterium-based metabolic regulation.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122901"},"PeriodicalIF":12.8,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491861","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":"A Sr@Ag-based spatiotemporal and step-release scaffold against chronic osteomyelitis, fabricated by coaxial 3D-printing","authors":"Jingyun Wang ,&nbsp;Qin Zhang ,&nbsp;Hetong Wang ,&nbsp;Chunlin Liu ,&nbsp;Le Jiang ,&nbsp;Wanting Liu ,&nbsp;Yixian Wu ,&nbsp;Yifan Wang ,&nbsp;Vivian ,&nbsp;Hao Yan ,&nbsp;Jun Lin ,&nbsp;Xiaodan Sun","doi":"10.1016/j.biomaterials.2024.122899","DOIUrl":"10.1016/j.biomaterials.2024.122899","url":null,"abstract":"<div><div>Chronic osteomyelitis (OM) represents a severe and persistent infectious bone disease. Effective treatment requires controlled anti-inflammatory releases and bone regeneration across disease phases. A Sr@Ag-based scaffold was successfully printed, featuring micron-scale coaxial fibers containing Ag-doped hydroxyapatite (HA) in the outer layer of PLLA and Sr-doped HA in the inner layer of PLLA, facilitating the spatiotemporal and sequential release of Ag and Sr ions during OM treatment. Most antibacterial agent (Ag) was released during the first 20 days, followed by a slow-release plateau over the next 40 days in phosphate-buffered saline solution (PBS). Meanwhile, the pro-angiogenic agent (Sr) was released in minimal amounts during the initial 20 days, followed by a rapid and considerable release in the following 40 days. The coaxial design effectively inhibited the growth of Staphylococcus aureus and Escherichia coli while preserving the viability of bone cells. The ion-based scaffold exhibited broad-spectrum antibacterial effects and enhanced bone-regenerating gene expression in a complex air-bacteria environment. The Sr@Ag-based coaxial scaffold demonstrated effective antibacterial activity during the early stage and exhibited excellent non-toxic bone regeneration results during the middle and late stages <em>in vivo</em>. This work offered a promising treatment strategy through sequential anti-inflammatory and pro-osteogenic effects for infectious bone-defect diseases.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122899"},"PeriodicalIF":12.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491857","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":"A MnO2 nanosheets doping double crosslinked hydrogel for cartilage defect repair through alleviating inflammation and guiding chondrogenic differentiation","authors":"Feilong Zhao ,&nbsp;Zhibo Jia ,&nbsp;Liyang Zhang ,&nbsp;Guodong Liu ,&nbsp;Junfei Li ,&nbsp;Jianming Zhao ,&nbsp;Yajie Xie ,&nbsp;Lu Chen ,&nbsp;Hongyu Jiang ,&nbsp;Wei He ,&nbsp;Aiyuan Wang ,&nbsp;Jiang Peng ,&nbsp;Yudong Zheng","doi":"10.1016/j.biomaterials.2024.122875","DOIUrl":"10.1016/j.biomaterials.2024.122875","url":null,"abstract":"<div><div>The inflammatory microenvironment and inferior chondrogenesis are major symptoms after cartilage defect. Although various modifications strategies associated with hydrogels exhibit remarkable capacity of pro-cartilage regeneration, the adverse effect by prolonging inflammation is still formidable to hamper potential biomedical applications of different hydrogel implants. Herein, inspired by the repair microenvironment of articular cartilage defects, an injectable, immunomodulatory, and chondrogenic L-MNS-CMDA hydrogel is prepared through grafting vinyl and catechol groups to chitosan macromolecules using amide reaction, then further loading MnO₂ nanosheets (MNS). The double crosslinking of photopolymerization and catechol oxidative polymerization endows L-MNS-CMDA hydrogel with preferable mechanical property, affording a suitable mechanical support for cartilage defect repair. Additionally, the robust tissue adhesion capability stemming from catechol groups guarantees the long-term retention of the hydrogel in the defect site. Meanwhile, L-MNS-CMDA hydrogel decomposes exogenous and intracellular H₂O₂ into O₂ and H₂O, to effectively alleviate cellular oxidative stress caused by long-term hypoxia. Under the synergies of catechol groups and MNS, L-MNS-CMDA hydrogel not only inhibits macrophages polarizing into M1 phenotype, but encourages them turn into M2 phenotype, thereby, reconstructing an immunization friendly microenvironment to ultimately enhance cartilage regeneration. Predictably, the hydrogel markedly induces rat bone marrow mesenchymal stem cells differentiating into chondrocytes by expressing abundant glycosaminoglycan and type II collagen. A cartilage defect model of rat knee joint indicates that L-MNS-CMDA hydrogel visually regulate the early inflammatory response of post-implantation, and facilitate cartilage regeneration and recovery of joint function after 12 weeks of post-implantation. All in all, this multifunctional L-MNS-CMDA hydrogel exhibits superior immunomodulatory and chondrogenic properties, holding immense clinical potential in the treatment of cartilage defects.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"314 ","pages":"Article 122875"},"PeriodicalIF":12.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491856","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}