Materials Today Bio最新文献

{"title":"Portable direct spraying porous nanofibrous membranes stent-loaded polymyxin B for treating diabetic wounds with difficult-to-heal gram-negative bacterial infections","authors":"Xiaolan Ou ,&nbsp;Wenlai Guo ,&nbsp;Heng Tian ,&nbsp;Daojiang Yu ,&nbsp;Rui Li ,&nbsp;Guanghui Gao ,&nbsp;Wenrui Qu","doi":"10.1016/j.mtbio.2024.101365","DOIUrl":"10.1016/j.mtbio.2024.101365","url":null,"abstract":"<div><div>Gram-negative bacteria infections in diabetic wounds are complicated to control, leading to amputation and even death in severe cases. There is an urgent need to develop effective therapeutic strategies. In recent years, electrospinning has attracted much attention due to its resemblance to extracellular matrix (ECM), which can regulate local cellular proliferation, migration, differentiation, etc.; however, its use is limited by its high cost and difficulty in transportation. This study proposes a portable direct-injection porous fibre scaffold containing polymyxin B (PMB) for local slow release for treating diabetic wounds infected with difficult-to-heal Gram-negative bacteria. The handheld portable electrospinner is lightweight and easy to operate and can be directly sprayed in situ to cover wounds with irregular shapes and sizes. When covering the wound in situ, the PVB/PVP nanofiber membrane can protect it from the external environment. Meanwhile, the nanofiber membrane dressing has a porosity of 20 % and a controlled drug-loading capacity. What's more, the evaluation of a whole skin defect model of type II diabetes mellitus infected with Gram-negative bacteria showed that the PMB-loaded nanofiber membrane could effectively inhibit Gram-negative bacteria infection, promote collagen deposition and re-epithelialization, and regulate the polarization of M1-type macrophages to M2-type macrophages, thereby controlling inflammation and promoting vascular regeneration, and significantly accelerating the healing of diabetic wounds. Overall, portable direct-injection porous fibre scaffold-loaded drugs are essential for healing difficult-to-heal wounds as local slow-release drug delivery.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101365"},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743002","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":"Killing two birds with one stone: Siglec-15 targeting integrated bioactive glasses hydrogel for treatment of breast cancer bone metastasis","authors":"Chengkuan Liu ,&nbsp;Yangui Zhong ,&nbsp;Haibo Huang ,&nbsp;Siyuan Lan ,&nbsp;Jing Li ,&nbsp;Deqiu Huang ,&nbsp;Wen Zhang","doi":"10.1016/j.mtbio.2024.101362","DOIUrl":"10.1016/j.mtbio.2024.101362","url":null,"abstract":"<div><div>Bone metastasis is a fatal consequence of breast cancer that occurs when patients fail to respond to conventional therapies and mainly result from a vicious cycle involving dysregulated bone homeostasis and uncontrolled tumor growth. Recent research has underscored the significance of Siglec-15, a membrane protein implicated in immunosuppression and osteoclast generation. Targeting Siglec-15 may disrupt the “vicious cycle” that causes bone metastases in patients with breast cancer. Herein, we explored the efficacy of targeting Siglec-15 in conjunction with photothermal chemotherapy to impede the progression of bone metastatic during breast cancer and repair tumor-induced osteolysis. First, we formulated an injectable photothermal bioactive glass (BG)-based hydrogel for the local delivery of Siglec-15 shRNA and doxorubicin. The results demonstrated that the hydrogel could kill tumor cells directly through photothermal chemotherapy, provoke intense immune responses and improve the local immunosuppressive microenvironment, which could effectively prevent tumor metastasis and recurrence in a murine model. The combined effect of BGs and Siglec15 shRNA can normalize dysregulated bone homeostasis at the bone metastasis site and significantly reduced bone destruction. Overall, the use of Siglec-15-targeting integrated BG hydrogels may provide a promising therapeutic strategy for treating bone metastasis caused by breast cancer.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101362"},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743006","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":"Idarubicin-loaded degradable hydrogel for TACE therapy enhances anti-tumor immunity in hepatocellular carcinoma","authors":"Xiaokai Zhang ,&nbsp;Xiujiao Deng ,&nbsp;Jizhou Tan ,&nbsp;Haikuan Liu ,&nbsp;Hong Zhang ,&nbsp;Chengzhi Li ,&nbsp;Qingjun Li ,&nbsp;Jinxue Zhou ,&nbsp;Zeyu Xiao ,&nbsp;Jiaping Li","doi":"10.1016/j.mtbio.2024.101343","DOIUrl":"10.1016/j.mtbio.2024.101343","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is a common and deadly cancer, often diagnosed at advanced stages, limiting surgical options. Transcatheter arterial chemoembolization (TACE) is a primary treatment for inoperable and involves the use of drug-eluting microspheres to slowly release chemotherapy drugs. However, patient responses to TACE vary, with some experiencing tumor progression and recurrence. Traditional TACE uses agents like oil-based drug emulsions and polyvinyl alcohol particles, which can permanently block blood vessels and increase tumor hypoxia. Additionally, TACE can suppress the immune system by reducing immune cell numbers and function, contributing to poor treatment outcomes. New approaches, like TACE using degradable starch microspheres and hydrogel-based materials, offer the potential to create different tumor environments that could improve both safety and efficacy. In our research, we developed a composite hydrogel (IF@Gel) made of Poloxamer-407 gel and Fe₃O₄ nanoparticles, loaded with idarubicin, to use as an embolic material for TACE in a rat model of orthotopic HCC. We observed promising therapeutic effects and investigated the impact on the tumor immune microenvironment, focusing on the role of immunogenic cell death (ICD). The composite hydrogel demonstrated excellent potential as an embolic material for TACE, and IF@Gel-based TACE demonstrated significant efficacy in rat HCC. Furthermore, our findings highlight the potential synergistic effects of ICD with anti-PD-L1 therapy, providing new insights into HCC treatment strategies. This study aims to provide improved treatment options for HCC and to deepen our understanding of the mechanisms of TACE and tumor environment regulation.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101343"},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743001","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":"Treating acute lung injury through scavenging of cell-free DNA by cationic nanoparticles","authors":"Ziyan Huang ,&nbsp;Cong Wei ,&nbsp;Hanbin Xie ,&nbsp;Xue Xiao ,&nbsp;Tienan Wang ,&nbsp;Yihan Zhang ,&nbsp;Yongming Chen ,&nbsp;Ziqing Hei ,&nbsp;Tianyu Zhao ,&nbsp;Weifeng Yao","doi":"10.1016/j.mtbio.2024.101360","DOIUrl":"10.1016/j.mtbio.2024.101360","url":null,"abstract":"<div><div>Acute lung injury (ALI) and acute respiratory distress syndrome are life-threatening conditions induced by inflammatory responses, in which cell-free DNA (cfDNA) plays a pivotal role. This study investigated the therapeutic potential of biodegradable cationic nanoparticles (cNPs) in alleviating ALI. Using a mouse model of lipopolysaccharide-induced ALI, we examined the impact of intravenously administered cNPs. Our findings indicate that cNPs possess robust DNA binding capability, enhanced accumulation in inflamed lungs, and a favorable safety profile <em>in vivo</em>. Furthermore, cNPs attenuate the inflammatory response in LPS-induced ALI mice by scavenging cfDNA, mainly derived from neutrophil extracellular traps, and activating the macrophage-mediated cGAS-STING pathway. The findings suggest a potential treatment for ALI by targeting cfDNA with cNPs. This approach has demonstrated efficacy in mitigating lung injury and merits further exploration.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101360"},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743005","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":"Scalable fabrication of freely shapable 3D hierarchical Cu-doped hydroxyapatite scaffolds via rapid gelation for enhanced bone repair","authors":"Hui Yang ,&nbsp;Sirui Huang ,&nbsp;Xinwei Zhu ,&nbsp;Yasi Chen ,&nbsp;Chunming Xu ,&nbsp;Ruohan Li ,&nbsp;Pan Bu ,&nbsp;Yufan Jiang ,&nbsp;Changwei Li ,&nbsp;Jie Yang ,&nbsp;Zhenyi Chen ,&nbsp;Weijie Peng ,&nbsp;Lin Liu","doi":"10.1016/j.mtbio.2024.101370","DOIUrl":"10.1016/j.mtbio.2024.101370","url":null,"abstract":"<div><div>Critical-sized bone defects present a formidable challenge in tissue engineering, necessitating innovative approaches that integrate osteogenesis and angiogenesis for effective repair. Inspired by the hierarchical porous structure of natural bone, this study introduces a novel method for the scalable production of ultra-long, copper-doped hydroxyapatite (Cu-HAp) fibers, utilizing the rapid gelation properties of guar gum (GG) under controlled conditions. These fibers serve as foundational units to fabricate three-dimensional porous scaffolds with a biomimetic hierarchical architecture. The scaffolds exhibit a broad pore size distribution (1–500 μm) and abundant nanoporous features, mimicking the native bone extracellular matrix. Physicochemical characterization and <em>in vitro</em> assays demonstrated that the copper doping significantly enhanced osteogenic and angiogenic activities, with optimized concentrations (0.8 % and 1.2 % Cu) facilitating the upregulation of osteogenesis-related genes and proteins, as well as promoting endothelial cell proliferation. <em>In vivo</em> studies further confirmed the scaffolds' efficacy, with the 1.2Cu-HAp group showing a remarkable increase in bone regeneration (bone volume/total volume ratio: 35.7 ± 1.87 %) within the defect site. This research offers a promising strategy for the rapid fabrication of multifunctional scaffolds that not only support bone tissue repair but also actively accelerate the healing process through enhanced vascularization.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101370"},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743004","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 three-phase strategy of bionic drug reservoir scaffold by 3D printing and layer-by-layer modification for chronic relapse management in traumatic osteomyelitis","authors":"Yutong Zhang ,&nbsp;Tongtong Xu ,&nbsp;Tieshu Li ,&nbsp;Hening Chen ,&nbsp;Guangzhe Xu ,&nbsp;Wenxin Hu ,&nbsp;Yongting Li ,&nbsp;Yue Dong ,&nbsp;Zhihui Liu ,&nbsp;Bing Han","doi":"10.1016/j.mtbio.2024.101356","DOIUrl":"10.1016/j.mtbio.2024.101356","url":null,"abstract":"<div><div>We have developed a novel three-phase strategy for osteomyelitis treatment, structured into three distinct phases: the “strong antimicrobial” phase, the “monitoring and osteogenesis” phase and the “bone repair” phase. To implement this staged therapeutic strategy, we engineered a bionic drug reservoir scaffold carrying a dual-drug combination of antimicrobial peptides (AMPs) and simvastatin (SV). The scaffold integrated a bilayer gel drug-carrying structure, based on an induced membrane and combined with a 3D-printed rigid bone graft using a layer-by-layer modification strategy. The mechanical strength of the composite scaffold (73.40 ± 22.44 MPa) is comparable to that of cancellous bone. This scaffold enables controlled, sequential drug release through a spatial structure design and nanoparticle drug-carrying strategy. AMPs are released rapidly, with the release efficiency of 74.90 ± 8.19 % at 14 days (pH = 7.2), thus enabling rapid antimicrobial therapy. Meanwhile, SV is released over a prolonged period, with a release efficiency of 98.98 ± 0.05 % over 40 days in vitro simulations, promoting sustained osteogenesis and facilitating the treatment of intracellular infections by activating macrophage extracellular traps (METs). The antimicrobial, osteogenic and immunomodulatory effects of the scaffolds were verified through in vitro and in vivo experiments. It was demonstrated that composite scaffolds were able to combat the chronic recurrence of osteomyelitis after debridement, by providing rapid sterilization, stimulating METs formation, and supporting osteogenic repair.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101356"},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743003","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":"Microenvironment-responsive injectable hydrogel for neuro-vascularized bone regeneration","authors":"Wanshun Wang ,&nbsp;Hu Chen ,&nbsp;Jiacong Xiao ,&nbsp;Dan Luo ,&nbsp;Yonghui Hou ,&nbsp;Jiheng Zhan ,&nbsp;Yu Hou ,&nbsp;Xing Li ,&nbsp;Huili Yang ,&nbsp;Shudong Chen ,&nbsp;Dingkun Lin","doi":"10.1016/j.mtbio.2024.101369","DOIUrl":"10.1016/j.mtbio.2024.101369","url":null,"abstract":"<div><div>Bone is a richly innervated and vascularized tissue, whereas nerve-vascular network reconstruction was often ignored in biomaterial design, resulting in delayed or incomplete bone healing. Inspired by the bone injury microenvironments, here we report a controllable drug delivery strategy using a pH and reactive oxygen species (ROS) dual-response injectable hydrogel. Based on the dynamic borate ester bond covalent crosslinking, nano-hydroxyapatite (HA) and curculigoside (CCG) are integrated into PVA/TSPBA (PT) to construct a responsive injectable hydrogel (PTHC), which scavenges excessive ROS from the injury microenvironment and responsively releases HA and CCG, providing favorable homeostasis and <em>in situ</em> sustained release drug delivery system for bone repair. Additionally, PTHC hydrogel can alleviate ROS-mediated intracellular oxidative and exhibit multiple biological activities of angiogenesis, neurogenesis, and osteogenesis. Furthermore, it reconstructs the microvascular network, accelerates sensory nerve repair, secretes neurotransmitters and bioactive factors, and improves neuro-vascularized bone regeneration. This multi-bioactive injectable hydrogel system offers a promising advance in therapeutic materials for bone repair.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101369"},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743009","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":"99mTc/90Y radiolabeled biodegradable gel microspheres for lung shutting fraction assessment and radioembolization in hepatocellular carcinoma theranostics","authors":"Yi Dong ,&nbsp;Lingling Yin ,&nbsp;Jintao Huang ,&nbsp;Di Hu ,&nbsp;Jing Sun ,&nbsp;Zhe Zhang ,&nbsp;Zhihao Li ,&nbsp;Bin-Yan Zhong ,&nbsp;Ran Zhu ,&nbsp;Guanglin Wang","doi":"10.1016/j.mtbio.2024.101367","DOIUrl":"10.1016/j.mtbio.2024.101367","url":null,"abstract":"<div><div>Transarterial radioembolization (TARE) is a well-established clinical therapy for the treatment of patients with intermediate to advanced hepatocellular carcinoma (HCC) or those who are ineligible for radical treatment. However, commercialized radioactive microspheres still have some issues, such as high density, complicated preparation, non-biodegradability. Furthermore, the use of different radioactive microspheres during TARE and lung shunt fraction assessment has led to inconsistencies in biodistribution in certain cases. This study employed biodegradable hyaluronic acid (HA) as the backbone and modified with bisphosphonate and methacrylic acid to prepare biodegradable gel microspheres (HAMS) using the water-in-oil emulsification and photo-crosslinking for labeling the diagnostic radionuclide of ^99mTc and therapeutic radionuclide of ⁹⁰Y. Both ^99mTc radiolabeled HAMS (^99mTc-HAMS) and radiolabeled ⁹⁰Y-HAMS (⁹⁰Y-HAMS) were highly efficient in radiolabeling and exhibited excellent radiostability <em>in vitro</em> and <em>in vivo</em>. ^99mTc-HAMS are highly effective in assessing the LSF, while ⁹⁰Y-HAMS, administered though TARE, are effective in inhibiting the growth of in situ HCC without any side effects. Both ^99mTc-HAMS and ⁹⁰Y-HAMS have promising clinical applications in HCC theranostics.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101367"},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743007","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":"Enhanced therapeutic potential of a self-healing hyaluronic acid hydrogel for early intervention in osteoarthritis","authors":"Dongze Wu ,&nbsp;Shuhui Yang ,&nbsp;Zhe Gong ,&nbsp;Xinxin Zhu ,&nbsp;Juncong Hong ,&nbsp;Haitao Wang ,&nbsp;Wenbin Xu ,&nbsp;Juncheng Lai ,&nbsp;Xiumei Wang ,&nbsp;Jiye Lu ,&nbsp;Xiangqian Fang ,&nbsp;Guoqiang Jiang ,&nbsp;Jinjin Zhu","doi":"10.1016/j.mtbio.2024.101353","DOIUrl":"10.1016/j.mtbio.2024.101353","url":null,"abstract":"<div><div>Osteoarthritis (OA) is characterized by symptoms such as abnormal lubrication function of synovial fluid and heightened friction on the cartilage surface in its early stages, prior to evident cartilage damage. Current early intervention strategies employing lubricated hydrogels to shield cartilage from friction often overlook the significance of hydrogel-cartilage adhesion and enhancement of the cartilage extracellular matrix (ECM). Herein, we constructed a hydrogel based on dihydrazide-modified hyaluronic acid (HA) (AHA) and catechol-conjugated aldehyde-modified HA (CHA), which not only adheres to the cartilage surface as an effective lubricant but also improves the extracellular environment of chondrocytes in OA. Material characterization experiments on AHA/CHA hydrogels with varying concentrations validated their exceptional self-healing capabilities, superior injectability and viscoelasticity, sustained adhesion strength to cartilage, and a low friction coefficient. Chondrocytes exhibited robust adhesion and proliferation on the AHA/CHA hydrogel surface, with the upregulation of cartilage matrix protein expression. Intra-articular injection of AHA/CHA hydrogels was performed following destabilization of the medial meniscus (DMM) surgery in mice to assess its protective effect on cartilage. The AHA/CHA hydrogel effectively attenuated the degree of cartilage wear, facilitated chondrocytes' anabolic metabolism, and restored the ECM of cartilage. Therefore, the AHA/CHA hydrogel emerges as a promising therapeutic approach in clinical practices of OA treatment.</div></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"Article 101353"},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142743008","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":"Enhanced sclerotherapy for vascular malformations: A dual-mechanism approach using in-situ forming PATDs gel.","authors":"Jizhuang Ma, Wenhan Li, Yu Ding, Yongfeng Chen, Xiaoyu Huang, Tong Yu, Di Song, Haoran Niu, Bao Li, Huichao Xie, Keda Zhang, Tianzhi Yang, Xiaoyun Zhao, Xinggang Yang, Pingtian Ding","doi":"10.1016/j.mtbio.2024.101376","DOIUrl":"https://doi.org/10.1016/j.mtbio.2024.101376","url":null,"abstract":"<p><p>Vascular malformations are common vascular lesions in infants and seriously affect their health and quality of life. Vascular sclerotherapy is an effective treatment for vascular malformations. However, current sclerosants have difficulty achieving both high efficiency and low toxicity, and their dosing forms make it difficult to achieve long-term retention in the affected blood vessels. Therefore, exploring a safe and effective sclerosant and its delivery strategy is the key to clinical sclerotherapy. To address the above issues, this study developed sclerosants that could form an in-situ gel based on a dual mechanism of vascular injury and plasmin (PLA) inhibition. By linking the non-ionic surfactant sclerosant polyoxyethylene alkyl ether (PAs) and the PLA inhibitor tranexamic acid (TA) through an ester bond, a cationic surfactant sclerosant polyoxyethylene alkylether tranexamate derivatives (PATDs) were constructed. The cationic charge of PATDs enhanced its cytotoxicity to HUVEC-TIE2-L914F cells, and the ester bond of PATDs could be degraded by esterase in the blood, reducing its systemic toxicity. The degradation product TA inhibited the activation of the PLA-matrix metalloproteinase (MMPs) system induced by vascular injury, thereby promoting the deposition of collagen and the proliferation and differentiation of fibroblasts to promote vascular fibrosis. In addition, an injectable solution (PATDs/GA) was prepared by mixing PATDs with glycerol formaldehyde (GA), and PATDs/GA could form a low-molecular-weight gel automatically in an aqueous solution, which was beneficial to increase its retention in the affected blood vessels and reduce the risk of drug entering non-targeted sites. At the same time, this gel automatically dissolved, reducing the risk of immune rejection caused by long-term retention. This study provided a new and precise approach for the treatment of vascular sclerosis with high efficiency and low toxicity.</p>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":"29 ","pages":"101376"},"PeriodicalIF":8.7,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854664","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}