Bioactive Materials最新文献

{"title":"Tailoring hyaluronic acid hydrogels: Impact of cross-linker length and density on skin rejuvenation as injectable dermal fillers and their potential effects on the MAPK signaling pathway suppression","authors":"Mohanapriya Murugesan ,&nbsp;Ramya Mathiyalagan ,&nbsp;Zelika Mega Ramadhania ,&nbsp;Jinnatun Nahar ,&nbsp;Cuong Hung Luu ,&nbsp;V.H. Giang Phan ,&nbsp;Deok Chun Yang ,&nbsp;Qihui Zhou ,&nbsp;Se Chan Kang ,&nbsp;Thavasyappan Thambi","doi":"10.1016/j.bioactmat.2025.03.002","DOIUrl":"10.1016/j.bioactmat.2025.03.002","url":null,"abstract":"<div><div>Hyaluronic acid (HA) hydrogels, obtained through cross-linking, provide a stable 3D environment that is important for controlled delivery and tissue engineering applications. Cross-linking density has a significant impact on the physicochemical properties of hydrogels, including their shape stability, mechanical stiffness and macromolecular diffusivity. However, often cross-linking chemistries require photoinitiator and catalyst that may be toxic and cause unwanted tissue response. Here, we prepared a series of HA hydrogel with varying cross-linker length and cross-linking density, which can be obtained by altering the feed ratio of three different cross-linkers from small molecules to macromolecules (e.g., 1,4-butanediol diglycidyl ether (BDDE), ferulic acid (FA), pluronic (PLU)), to ameliorate skin wrinkles in mice models. HA cross-linked with FA and PLU exhibited enzyme and temperature-dependent sol-to-gel phase transition, respectively, and the gels possess good injectability. In vitro test confirmed that HA hydrogels co-cultured with RAW 264.7 and HDF cells showed good biocompatibility. In particular, HA cross-linked with PLU stimulated the growth of HDF cells and HaCaT cells. HA cross-linked with PLU suppressed the expression levels of proteins involved in collagen degradation including mitogen-activated protein kinases (ERK, JNK, p38) and matrix metalloproteases (MMP-1, MMP-3, and MMP-9) resulting in increased deposition of Collagen I. The free-flowing sols of HA hydrogel precursors are subcutaneously injected into the back of BALB/c mice and form stable gels at the dermis layer and found to be non-toxic. More importantly, HA hydrogel cross-linked with PLU showed an enhanced anti-wrinkling effect in the wrinkled mice model. Thus, properties of HA hydrogels such as injectability, biocompatibility, and good anti-wrinkling effect altered through varying cross-linking density must be considered in the context of soft tissue engineering applications.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 154-171"},"PeriodicalIF":18.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578902","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":"Enhancing PD-1 blockade in NSCLC: Reprogramming tumor immune microenvironment with albumin-bound statins targeting lipid rafts and mitochondrial respiration","authors":"Na Chen ,&nbsp;Zhanfeng Li ,&nbsp;Heyuan Liu ,&nbsp;Aimin Jiang ,&nbsp;Liqiang Zhang ,&nbsp;Siqi Yan ,&nbsp;Wangxiao He ,&nbsp;Jingyue Yang ,&nbsp;Tianya Liu","doi":"10.1016/j.bioactmat.2025.03.003","DOIUrl":"10.1016/j.bioactmat.2025.03.003","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) has shown limited response to immunotherapy, primarily due to an immunosuppressive tumor microenvironment characterized by hypoxia and lipid raft formation, which together inhibit T-cell infiltration and function, impeding effective immune responses. To address these challenges, we developed Abstatin, an albumin-bound fluvastatin formulation that targets lipid raft disruption and mitochondrial respiration inhibition, aiming to reduce hypoxia and destabilize lipid rafts to enhance T-cell activity within the tumor. Using bioinformatics analysis, <em>in vitro</em> assays, and <em>in vivo</em> studies in both murine and humanized PDX models, we demonstrated that Abstatin reprograms the NSCLC microenvironment by concurrently lowering hypoxia levels and lipid raft integrity, thereby restoring T-cell infiltration, enhancing cytotoxic T-cell function, and ultimately improving response to Anti-PD-1 therapy. Results showed that Abstatin significantly amplifies Anti-PD-1 efficacy with minimal toxicity, indicating a favorable safety profile for clinical use. This study highlights Abstatin as a promising immunotherapy adjuvant that addresses critical barriers in NSCLC by modulating metabolic pathways linked to immune resistance. Abstatin's approach, which combines modulation of cellular metabolism with immune sensitization, broadens the potential of immunotherapy and provides a practical, scalable strategy to enhance treatment outcomes in NSCLC and potentially other tumors, offering insights into combinatory cancer therapies.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 140-153"},"PeriodicalIF":18.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563125","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":"Zn-DHM nanozymes regulate metabolic and immune homeostasis for early diabetic wound therapy","authors":"Shuo Zhang ,&nbsp;Xinyu Zhao ,&nbsp;Wei Zhang ,&nbsp;Xiaolong Wei ,&nbsp;Xu-Lin Chen ,&nbsp;Xianwen Wang","doi":"10.1016/j.bioactmat.2025.02.041","DOIUrl":"10.1016/j.bioactmat.2025.02.041","url":null,"abstract":"<div><div>Diabetic wounds heal slowly or incompletely because of the microenvironment of hyperglycemia, high levels of reactive oxygen species (ROS), excessive inflammation, metabolic disorders and immune dysregulation, and the therapeutic effect is limited only by disruption of the reactive oxygen species (ROS)-inflammation cascade cycle. Here, a novel metal-polyphenolic nanozyme (Zn-DHM NPs) synthesized by the coordination of Zn²⁺ with dihydromyricetin (DHM) was designed, which not only has a superior ability to scavenge ROS and promote cell proliferation and migration but also functions in the regulation of metabolism and immune homeostasis. <em>In vitro</em> and <em>in vivo</em> experiments and RNA sequencing analyses revealed that Zn-DHM NPs could increase the levels of intracellular SOD and CAT enzymes to scavenge ROS and maintain the level of the mitochondrial membrane potential to reduce apoptosis. In terms of glucose metabolism, Zn-DHM NPs downregulated excessive levels of intracellular glucose and HK2, inhibited excessive glycolysis and downregulated the AGE-RAGE pathway to restore cellular function. In terms of immune regulation, Zn-DHM NPs not only downregulate M1/M2 levels to promote tissue repair but also maintain Th17/Treg homeostasis, downregulate the IL-17 signaling pathway to reduce inflammation, and upregulate FOXP3 to maintain immune homeostasis, thereby promoting early wound healing in diabetic mice. The development of Zn-DHM NPs provides a new therapeutic target to promote early healing of diabetic wounds.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 63-84"},"PeriodicalIF":18.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548691","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":"Mesenchymal stromal/stem cell spheroid-derived extracellular vesicles advance the therapeutic efficacy of 3D-printed vascularized artificial liver lobules in liver failure treatment","authors":"Jiabin Zhang ,&nbsp;Xiaodie Chen ,&nbsp;Yurong Chai ,&nbsp;Yuanyuan Jin ,&nbsp;Fenfang Li ,&nbsp;Chenya Zhuo ,&nbsp;Yanteng Xu ,&nbsp;Haixia Wang ,&nbsp;Enguo Ju ,&nbsp;Yeh-Hsing Lao ,&nbsp;Xi Xie ,&nbsp;Mingqiang Li ,&nbsp;Yu Tao","doi":"10.1016/j.bioactmat.2025.02.042","DOIUrl":"10.1016/j.bioactmat.2025.02.042","url":null,"abstract":"<div><div>Acute liver failure (ALF) is a highly lethal condition characterized by massive tissue necrosis, excessive oxidative stress, and serious inflammatory storms, necessitating prompt medical intervention. Although hepatocyte-like cells (HLCs) derived from mesenchymal stromal/stem cells (MSCs) offer a promising alternative cell source for hepatocyte therapy, their low <em>in-vivo</em> integration and differentiation efficiency may compromise the eventual therapeutic efficacy. To this end, MSCs are bioengineered into multicellular spheroids in the present study. The proteomic analyses and experimental results reveal that extracellular vesicles (EVs) derived from these MSC spheroids (SpEV) contain abundant highly expressed bioactive proteins and can be efficiently endocytosed by recipient cells, resulting in enhanced pro-angiogenic and antioxidative effects. In addition, MSC spheroids exhibit superior hepatic cell differentiation compared to an equivalent number of dissociated single MSCs, particularly when being co-cultured with hexagonally patterned endothelial cells in a liver lobule-like arrangement. Following orthotopic implantation in the mouse model, the enhanced paracrine effects of SpEV, combined with an immunoregulatory decellularized extracellular matrix hydrogel carrier and functional artificial liver lobules (ALL), synergically contribute to the effective amelioration of ALF, highlighting the substantial potential for clinical translation.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 121-139"},"PeriodicalIF":18.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143563124","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":"From hard tissues to beyond: Progress and challenges of strontium-containing biomaterials in regenerative medicine applications","authors":"Liyun Wang ,&nbsp;Shengjie Jiang ,&nbsp;Jialiang Zhou ,&nbsp;Mazaher Gholipourmalekabadi ,&nbsp;Yuan Cao ,&nbsp;Kaili Lin ,&nbsp;Yu Zhuang ,&nbsp;Changyong Yuan","doi":"10.1016/j.bioactmat.2025.02.039","DOIUrl":"10.1016/j.bioactmat.2025.02.039","url":null,"abstract":"<div><div>Tissue engineering and regenerative medicine have emerged as crucial disciplines focused on the development of new tissues and organs to overcome the limitations of traditional treatments for tissue damage caused by accidents, diseases, or aging. Strontium ion (Sr²⁺) has garnered significant attention for its multifaceted role in promoting regeneration medicine and therapy, especially in bone tissue regeneration. Recently, numerous studies further confirm that Sr²⁺ also plays a critical in soft tissue regeneration. This review firstly summarizes the influence of Sr²⁺ on critical biological processes such as osteogenesis, angiogenesis, immune modulation, matrix synthesis, mineralization, and antioxidative defence mechanisms. Then details the classification, properties, advantages, and limitations of Sr-containing biomaterials (SrBMs). Additionally, this review extends to the current applications of SrBMs in regenerative medicine for diverse tissues, including bone, cartilage, skeletal muscle, dental pulp, cardiac tissue, skin, hair follicles, etc. Moreover, the review addresses the challenges associated with current SrBMs and provides insights for their future designing and applications in regenerative medicine.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 85-120"},"PeriodicalIF":18.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548692","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":"A review: Carrier-based hydrogels containing bioactive molecules and stem cells for ischemic stroke therapy","authors":"Wenqi Yin ,&nbsp;Yuchi Jiang ,&nbsp;Guangrui Ma ,&nbsp;Bricard Mbituyimana ,&nbsp;Jia Xu ,&nbsp;Zhijun Shi ,&nbsp;Guang Yang ,&nbsp;Hong Chen","doi":"10.1016/j.bioactmat.2025.01.014","DOIUrl":"10.1016/j.bioactmat.2025.01.014","url":null,"abstract":"<div><div>Ischemic stroke (IS), a cerebrovascular disease, is the leading cause of physical disability and death worldwide. Tissue plasminogen activator (tPA) and thrombectomy are limited by a narrow therapeutic time window. Although strategies such as drug therapies and cellular therapies have been used in preclinical trials, some important issues in clinical translation have not been addressed: low stem cell survival and drug delivery limited by the blood-brain barrier (BBB). Among the therapeutic options currently sought, carrier-based hydrogels hold great promise for the repair and regeneration of neural tissue in the treatment of ischemic stroke. The advantage lies in the ability to deliver drugs and cells to designated parts of the brain in an injectable manner to enhance therapeutic efficacy. Here, this article provides an overview of the use of carrier-based hydrogels in ischemic stroke therapy and focuses on the use of hydrogel scaffolds containing bioactive molecules and stem cells. In addition to this, we provide a more in-depth summary of the composition, physicochemical properties and physiological functions of the materials themselves. Finally, we also outline the prospects and challenges for clinical translation of hydrogel therapy for IS.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 39-62"},"PeriodicalIF":18.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548681","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":"Topological cues of microparticles train stem cells for tissue repair via mechanotransduction","authors":"Jiannan Mao ,&nbsp;Yichang Xu ,&nbsp;Wenbo Wang ,&nbsp;Xiongwei Deng ,&nbsp;Yujian Hui ,&nbsp;Min Rui ,&nbsp;Jincheng Tang ,&nbsp;Wei Wang ,&nbsp;Yiyang Huang ,&nbsp;Liang Wu ,&nbsp;Kun Xi ,&nbsp;Yunrong Zhu ,&nbsp;Yong Gu ,&nbsp;Liang Chen","doi":"10.1016/j.bioactmat.2025.02.032","DOIUrl":"10.1016/j.bioactmat.2025.02.032","url":null,"abstract":"<div><div>Microspheres (MPs) and porous microspheres (PMPs) are the two most widely used microparticles in tissue engineering and stem cell therapy. However, how stem cells perceive the topological differences between them to regulate cell function remains to be unclear. Here, we systematically studied the changes in stem cell function under the action of MPs and PMPs and elucidated the related mechanisms. Our findings show that the porous structure of PMPs can be sensed by focal adhesions (FAs), which triggers the synthesis of F-actin to inhibit the phosphorylation and degradation of Yes-associated protein (YAP), while also transmitting stress to the nucleus through the contraction of F-actin, thereby enhancing the nuclear translocation of YAP protein. The activation of YAP significantly enhances the proliferation, osteogenesis, paracrine and glucose metabolism of BMSCs, making them exhibit stronger bone repair ability in both in vivo and in vitro experiments. In summary, this study provides a comprehensive and reliable understanding of the behavior of BMSCs in response to MPs and PMPs. It also deepens our understanding of the association between microparticles’ topological cues and biological functions, which will provide valuable guidance for the construction of bone tissue engineering (BTE) scaffolds.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 531-549"},"PeriodicalIF":18.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529444","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":"MXenes as emerging materials to repair electroactive tissues and organs","authors":"Keshav Narayan Alagarsamy ,&nbsp;Leena Regi Saleth ,&nbsp;Saravanan Sekaran ,&nbsp;Laura Fusco ,&nbsp;Lucia Gemma Delogu ,&nbsp;Maksym Pogorielov ,&nbsp;Açelya Yilmazer ,&nbsp;Sanjiv Dhingra","doi":"10.1016/j.bioactmat.2025.01.035","DOIUrl":"10.1016/j.bioactmat.2025.01.035","url":null,"abstract":"<div><div>Nanomaterials with electroactive properties have taken a big leap for tissue repair and regeneration due to their unique physiochemical properties and biocompatibility. MXenes, an emerging class of electroactive materials have generated considerable interest for their biomedical applications from bench to bedside. Recently, the application of these two-dimensional wonder materials have been extensively investigated in the areas of biosensors, bioimaging and repair of electroactive organs, owing to their outstanding electromechanical properties, photothermal capabilities, hydrophilicity, and flexibility. The currently available data reports that there is significant potential to employ MXene nanomaterials for repair, regeneration and functioning of electroactive tissues and organs such as brain, spinal cord, heart, bone, skeletal muscle and skin. The current review is the first report that compiles the most recent advances in the application of MXenes in bioelectronics and the development of biomimetic scaffolds for repair, regeneration and functioning of electroactive tissues and organs including heart, nervous system, skin, bone and skeletal muscle. The content in this article focuses on unique features of MXenes, synthesis process, with emphasis on MXene-based electroactive tissue engineering constructs, biosensors and wearable biointerfaces. Additionally, a section on the future of MXenes is presented with a focus on the clinical applications of MXenes.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 583-608"},"PeriodicalIF":18.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143534989","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":"Piezoelectric nanofilms fabricated by coaxial electrospun polycaprolactone/Barium titanate promote Achilles tendon regeneration by reducing IL-17A/NF-κB-mediated inflammation","authors":"Wufei Dai ,&nbsp;Qi Xu ,&nbsp;Qinglin Li ,&nbsp;Xiansong Wang ,&nbsp;Wenjie Zhang ,&nbsp;Guangdong Zhou ,&nbsp;Xu Chen ,&nbsp;Wei Liu ,&nbsp;Wenbo Wang","doi":"10.1016/j.bioactmat.2025.02.038","DOIUrl":"10.1016/j.bioactmat.2025.02.038","url":null,"abstract":"<div><div>Tendon injuries are often exacerbated by persistent inflammation, which hampers tissue regeneration. In this study, we developed a noninvasive, wirelessly controlled, and self-powered piezoelectric nanofilm fabricated by coaxial electrospinning of polycaprolactone (PCL) and tetragonal barium titanate nanoparticles (BTO), and investigated its roles in modulating inflammation and repairing Achilles tendon defects as well as the mechanism in a rat model. <em>In vitro</em> study and <em>in vivo</em> study upon subcutaneous implantation showed that the piezoelectric PCL/BTO nanofilms could inhibit M1 macrophage polarization and reduce the secretion of inflammatory factors. Moreover, when bridging an Achilles tendon defect, the nanofilms could promote tenogenic gene expression including collagen deposition, and collagen remodeling, facilitate functional tendon recovery and significantly reduce tissue inflammation by suppressing M1 macrophage polarization and promoting M2 polarization. Moreover, the piezoelectric stimulation could also enhance tendon regeneration by inhibiting angiogenesis, reducing lipid deposition, and decreasing ectopic ossification. Mechanistically, the piezoelectric nanofilms reduced tissue inflammation mainly via inhibiting the nuclear factor (NF)-κB signaling pathway that is mediated by interleukin (IL)-17A secreted from CD3⁺ T cells, and thus to reduce proinflammatory factors, such as IL-1β and IL-6, inducible nitric oxide synthase, monocyte chemoattractant protein-1, and tumor necrosis factor-α. These findings indicate the potential of piezoelectric stimulation in immunomodulation, and in promoting tendon regeneration via IL-17A/NF-κB-mediated pathway.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 1-22"},"PeriodicalIF":18.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519114","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":"Immune-modulated adhesive hydrogel for enhancing osteochondral graft adhesion and cartilage repair","authors":"Jiaqi Zhou ,&nbsp;Xiongfa Ji ,&nbsp;Yu Xue ,&nbsp;Wenjie Yang ,&nbsp;Guoqing Zhong ,&nbsp;Zhiyang Zhou ,&nbsp;Xingmei Chen ,&nbsp;Zehua Lei ,&nbsp;Teliang Lu ,&nbsp;Yu Zhang ,&nbsp;Ji Liu ,&nbsp;Limin Ma","doi":"10.1016/j.bioactmat.2025.02.035","DOIUrl":"10.1016/j.bioactmat.2025.02.035","url":null,"abstract":"<div><div>Osteochondral autograft transfer system (OATS) can effectively improve cartilage injuries by obtaining bone-cartilage grafts from healthy sites and implanting them into the defective areas. However, in up to 40 % of patients, the lack of a stable adhesive interface between the osteochondral graft and the normal tissue surface reduces the repair efficiency. In this work, we report an injectable and biocompatible poly (N-hydroxyethyl acrylamide-N-hydroxy succinimide)/Gelatin (PHE-Gel) hydrogel, featuring the instant formation of a tough bio-interface, which allows for robust adhesion with osteochondral grafts. Through physicochemical characterization, we found that a system composed of 10%PHE-Gel possesses superior interfacial toughness and excellent biocompatibility. In vitro, mechanistic studies and RNA-seq analysis had shown that 10%PHE-Gel promotes the expression of cartilage anabolic metabolism genes by upregulating the hypoxia-inducible factor alpha (HIF-α) signaling pathway and downregulating the tumor necrosis factor (TNF) signaling pathway. Dimethyloxalylglycine (DMOG) loaded liposome (DMOG-Lip) promotes the transition of M1 macrophages to M2 macrophages, shifting the microenvironment towards a pro-repair direction. Studies on a rabbit OATS model indicated that DMOG-Lip loaded 10%PHE-Gel (10%PHE-Gel@DMOG-Lip) effectively modulated the immune microenvironment, facilitated the repair of the hyaline cartilage, and inhibited further degeneration of cartilage. This composite hydrogel offers a promising solution for enhancing OATS repair in tissue engineering and has the potential to improve outcomes in cartilage restoration procedures.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"49 ","pages":"Pages 23-38"},"PeriodicalIF":18.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519115","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}