Bioactive Materials最新文献_第5页

Esophagus extracellular matrix with microenvironmental complexity for esophageal organoids 食管类器官微环境复杂性的食管细胞外基质

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-05 DOI: 10.1016/j.bioactmat.2025.12.046

Sewon Park , Eun Je Jeon , Won-Gun Koh , Seung-Woo Cho

Esophageal organoids have the potential to serve as promising therapeutics for esophageal mucosal damage, but their application remains largely unexplored. A critical initial step in this application involves addressing the challenges posed by Matrigel (MAT)-based conventional organoid culture, as its tumor-derived origin hinders clinical applications. In this study, we demonstrate the application of decellularized esophagus-derived extracellular matrix (EEM) to the culture and transplantation of esophageal organoids, inspired by excellent biocompatibility and esophageal mimicry of EEM. Our comprehensive proteomic analysis reveals that EEM recapitulates microenvironmental complexity suitable for esophageal organoids by providing diverse esophagus-specific proteins absent in MAT. Esophageal organoids grown in EEM hydrogel can expand through multiple passages and exhibit comparable or elevated expression of esophagus-related genes compared to those grown in MAT. The transplantation of esophageal organoids with EEM not only promotes epithelial regeneration but also mitigates fibrosis at the wound site in a mouse model of an esophageal ulcer. Furthermore, the protein profiles of esophageal tissues undergoing regeneration support the activation of wound healing following organoid transplantation. Taken together, the EEM-based approach for esophageal organoid culture and transplantation would pave the way for advancing esophageal organoid applications by providing a stable and refined matrix to replace MAT.

食管类器官有潜力作为治疗食管粘膜损伤的有前途的药物，但它们的应用在很大程度上仍未被探索。该应用的关键初始步骤是解决基于Matrigel （MAT）的传统类器官培养所带来的挑战，因为它的肿瘤来源阻碍了临床应用。在这项研究中，我们展示了脱细胞食管源性细胞外基质（EEM）在食管类器官培养和移植中的应用，灵感来自EEM出色的生物相容性和食管拟态性。我们的综合蛋白质组学分析显示，EEM通过提供MAT中缺乏的多种食管特异性蛋白质，重现了适合食管类器官的微环境复杂性。与MAT中生长的食管类器官相比，EEM水凝胶中生长的食管类器官可以通过多次传代扩张，并表现出相当或更高的食管相关基因表达食管溃疡小鼠模型伤口部位纤维化。此外，经历再生的食管组织的蛋白质谱支持类器官移植后伤口愈合的激活。综上所述，基于eem的食管类器官培养和移植方法将为食管类器官的应用铺平道路，因为它提供了一种稳定而精细的基质来替代MAT。

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引用次数: 0

Engineered LINC MIR503HG-loaded extracellular vesicles maintain stemness and pluripotency during long-term hiPSCs culture 在长期的hipsc培养过程中，装载了基因工程的LINC mir503hg的细胞外囊泡保持了干性和多能性

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-04 DOI: 10.1016/j.bioactmat.2025.12.023

Jiaqi Zhu , Xiaoren Zhu , Wei Feng , Yi Jin , Xinqi Ge , Yuxi Li , Xiaoxia Xue , Zhiwei Wang , Yang Xu , Yan Huang

The reduction of stemness and pluripotency during the prolonged culture of hiPSCs poses a significant challenge in regenerative medicine. This study identified LINC MIR503HG as a factor involved in maintaining hiPSCs stemness. Consequently, it developed a highly efficient delivery system based on ADSC-EVs, named MIR503HG-EVs, to optimize the culture strategy for hiPSCs. During the extended culture, MIR503HG-EV-treated hiPSCs developed into colonies with more compact morphology, an increased percentage of viable cells, as well as elevated OCT4, SOX2, and NANOG expression. Furthermore, these cells maintained their chromosomal integrity, as no karyotypic anomalies were detected. Mechanistic studies demonstrated that MIR503HG selectively bound AHCTF1 to facilitate the active nucleocytoplasmic transport of MYC mRNA. This resulted in significantly augmented MYC protein production, which activated the stemness regulatory network. Concurrently, MIR503HG-EVs mitigated the decline in differentiation potential of hiPSCs after several passages by modulating the chromatin accessibility of stemness transcription factors and modifying energy metabolism, including glycolysis and oxidative phosphorylation pathways. Moreover, treatment with MIR503HG-EVs significantly enhanced the differentiation efficiency of high-passage hiPSCs into definitive endoderm, pancreatic, and hepatic lineages, thereby achieving a level of proficiency comparable to that of low-passage clones. Overall, this study identified the addition of MIR503HG-EVs as a convenient, efficient, and safe approach for maintaining high-passage hiPSCs.

在长时间培养hipsc的过程中，干细胞的干性和多能性的降低对再生医学提出了重大挑战。本研究确定了LINC MIR503HG是维持hipsc干细胞稳定性的一个因素。因此，他们开发了一种基于adsc - ev的高效递送系统，命名为mir503hg - ev，以优化hipsc的培养策略。在长时间培养过程中，mir503hg - ev处理的hiPSCs发育成更致密的菌落，活细胞百分比增加，OCT4， SOX2和NANOG表达升高。此外，由于没有检测到核型异常，这些细胞保持了染色体的完整性。机制研究表明，MIR503HG选择性结合AHCTF1促进MYC mRNA的核质转运。这导致MYC蛋白的产生显著增加，从而激活了茎秆调节网络。同时，mir503hg - ev通过调节干性转录因子的染色质可及性和调节能量代谢，包括糖酵解和氧化磷酸化途径，减轻了hiPSCs在几代传代后分化潜力的下降。此外，mir503hg - ev处理显著提高了高传代hipsc向最终内胚层、胰腺和肝脏谱系的分化效率，从而达到了与低传代克隆相当的熟练程度。总体而言，本研究确定添加mir503hg - ev是维持高传代hiPSCs的一种方便、高效和安全的方法。

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引用次数: 0

Degradation behavior and biological properties of a novel biodegradable zinc alloy biliary stent 一种新型可生物降解锌合金胆道支架的降解行为和生物学特性

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-04 DOI: 10.1016/j.bioactmat.2025.12.022

Yuechuan Li , Chengchen Deng , Duanqiang Xiao , Chengyan Bai , Lebing Chang , Hongqing Feng , Haijun Zhang , Guixue Wang

Current biodegradable biliary stents remain inadequate for clinical demands. Zinc (Zn) alloys, exhibiting excellent mechanical properties, moderate degradation rates, and favorable biocompatibility, are potential materials for biodegradable biliary stents. In this study, trace boron (B) was added to Zn-0.8Cu alloy to enhance its mechanical properties and biocompatibility, and to investigate its suitability as biliary stent. The incorporation of 0.03 wt% boron significantly refined the grain size and introduced the bimodal organization, consequently enhancing the mechanical properties of Zn-0.8Cu alloy (As cast: yield strength, ultimate tensile strength, and elongation increased by 52.0 %, 42.5 %, and 153.8 %, respectively). Moreover, boron addition reduced the corrosion resistance of Zn-0.8Cu alloy and the surface became hydrophilic (water contact angle 70.75° ± 1.74°). In vitro evaluations revealed that the Zn-0.8Cu-0.03B alloy exhibited excellent biocompatibility and strongly inhibited the growth of Staphylococcus aureus and Escherichia coli. Finally, the Zn-0.8Cu-0.03B alloy stents maintained structural integrity in the rabbit common bile duct for 3 weeks, followed by accelerated degradation, and were completely degraded within 8 weeks. Zn-0.8Cu-0.03B alloy stents showed excellent biocompatibility in vivo, the degradation products were safely eliminated without causing biliary stricture or obstruction, and tissue hyperplasia induced by stent was effectively alleviated. In conclusion, this study expands the applications potential of Zn alloy in biomedicine and provides reference for developing new generation biodegradable biliary stents.

目前的可生物降解胆道支架仍不足以满足临床需求。锌合金具有优异的力学性能、适度的降解速率和良好的生物相容性，是生物可降解胆道支架的潜在材料。本研究通过在Zn-0.8Cu合金中加入微量硼(B)，增强其力学性能和生物相容性，探讨其作为胆道支架的适用性。0.03 wt%硼的加入显著细化了Zn-0.8Cu合金的晶粒尺寸，引入了双峰组织，从而提高了合金的力学性能（铸造时屈服强度、极限抗拉强度和延伸率分别提高了52.0%、42.5%和153.8%）。硼的加入降低了Zn-0.8Cu合金的耐蚀性，表面亲水（水接触角为70.75°±1.74°）。体外评价表明，锌-0.8 cu - 0.03b合金具有良好的生物相容性，对金黄色葡萄球菌和大肠杆菌的生长有较强的抑制作用。最后，Zn-0.8Cu-0.03B合金支架在兔胆总管内保持结构完整3周，随后加速降解，8周内完全降解。Zn-0.8Cu-0.03B合金支架在体内具有良好的生物相容性，降解产物安全消除，不会引起胆道狭窄或梗阻，有效减轻支架诱导的组织增生。总之，本研究拓展了锌合金在生物医学上的应用潜力，为开发新一代生物可降解胆道支架提供参考。

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引用次数: 0

Engineered atopic dermatitis models for recreating hypoxic conditions in atopic dermatitis microenvironments 在特应性皮炎微环境中重建缺氧条件的工程特应性皮炎模型

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-04 DOI: 10.1016/j.bioactmat.2025.12.045

Kyeong Seok Na , Jooyoung Park , Su Min Kim , Jina Lee , Eunji Lee , Wonjin Woo , Jungmin Choi , Lark Kyun Kim , Kyung Min Park

Atopic dermatitis (AD) is a chronic inflammatory condition with severe itching. The complex physiology and diverse pathogenesis of AD complicate the prediction of clinical outcomes. Therefore, it is essential to develop preclinical models closely mimicking features of AD. Herein, gelatin-based in situ crosslinkable hydrogel AD models are engineered replicating the characteristics of AD tissue. First, public data of patients with AD is used to confirm the following, using single-cell RNA sequencing analysis: (1) collagen type VI alpha 5 chain (COL6A5+) fibroblast expression in patient tissues, (2) cell interaction with dorsal root ganglions that induce itching, and (3) overexpression of hypoxia-related factors in AD tissues. Based on these characteristics, an artificial AD model is developed using gelatin-based in situ crosslinked hydrogels. 3D cell culture systems are fabricated by encapsulating cells within hydrogels, supporting 3D cell survival and growth. These models exhibit a hypoxic (pO₂ < 5 %) environment within the hydrogels, with upregulated expression of hypoxia-related genes. In these hydrogel-based skin models, the AD microenvironment is recreated, inducing immune responses and chronic hypoxia through IL-4 treatment and controlled oxygen concentration. Overexpression of itch-related factors, evaluation of drug response to treatment, and gene upregulation under hypoxic and immune conditions are also analyzed in the models. Our platforms are potential preclinical models for drug screening and fundamental research.

特应性皮炎（AD）是一种伴有严重瘙痒的慢性炎症性疾病。阿尔茨海默病复杂的生理和多样的发病机制使临床预后的预测复杂化。因此，开发与AD特征相近的临床前模型至关重要。在此，基于明胶的原位交联水凝胶AD模型被设计成复制AD组织的特征。首先，利用公开的AD患者数据，通过单细胞RNA测序分析，证实了以下情况：(1)患者组织中胶原型α - 5链（COL6A5+）成纤维细胞的表达，(2)细胞与背根神经节的相互作用诱导瘙痒，(3)AD组织中缺氧相关因子的过表达。基于这些特点，利用明胶基原位交联水凝胶建立了人工AD模型。3D细胞培养系统是通过将细胞包裹在水凝胶中来制造的，支持3D细胞的生存和生长。这些模型在水凝胶中表现出缺氧（pO2 < 5%）的环境，缺氧相关基因的表达上调。在这些基于水凝胶的皮肤模型中，AD微环境被重建，通过IL-4治疗和控制氧浓度诱导免疫反应和慢性缺氧。在模型中还分析了瘙痒相关因子的过表达、药物治疗反应的评估以及缺氧和免疫条件下基因的上调。我们的平台是药物筛选和基础研究的潜在临床前模型。

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引用次数: 0

Supramolecular helicity dependent osteogenesis and angiogenesis crosstalk of periodontal ligament stem cell 牙周韧带干细胞超分子螺旋度依赖性成骨和血管生成串扰

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-02 DOI: 10.1016/j.bioactmat.2025.12.057

Zhuohang Deng , Meijun Li , Yifan Wang , Wenjing Li , Zijian Gong , Peiwen Liao , Shengzhen Luo , Minghua Liu , Xuliang Deng

The two pillars supporting effective tissue regeneration are multipotent stem cells and matrix materials that direct differentiation. The chirality of the extracellular matrix is a key structural characteristic that affects stem cell fate. However, little is known about the effects of either molecular chirality or supramolecular helicity on the differentiation of periodontal ligament stem cells (PDLSCs), a safe and easily accessible stem cell source. Here, we constructed fibrils through the co-assembly of chiral amino acid derivative enantiomers (l/d-GC18) and a bridging pyrazine molecule. The helicity of the fibrils depends on both the molecular chirality of the amino acid and the stoichiometric ratio of the two components. Our results showed that molecular chirality and supramolecular helicity can act synergistically, with the left-handed fibrils assembled from l-GC18 and pyrazine promoting osteogenic differentiation of PDLSCs in vivo. Moreover, the chiral fibrils effectively promoted bone regeneration in both the calvarial and alveolar bone defect models. Interestingly, it was observed that left-handed fibrils induced integrin-dependent osteogenic differentiation, which in turn stimulated Piezo1-mediated, Vascular Endothelial Growth Factor (VEGF)-driven angiogenesis. These findings thus provide a blueprint for harnessing PDLSCs in next-generation regenerative therapeutics.

支持有效组织再生的两大支柱是多能干细胞和直接分化的基质材料。细胞外基质的手性是影响干细胞命运的关键结构特征。然而，对于分子手性或超分子螺旋度对牙周韧带干细胞（PDLSCs）分化的影响知之甚少，PDLSCs是一种安全且容易获得的干细胞来源。在这里，我们通过手性氨基酸衍生物对映体（l/d-GC18）和桥接吡嗪分子的共组装构建了原纤维。原纤维的螺旋度取决于氨基酸的分子手性和两种组分的化学计量比。结果表明，分子手性和超分子螺旋度可以协同作用，l-GC18和吡嗪组装的左旋原纤维在体内促进PDLSCs的成骨分化。此外，手性原纤维在颅骨和牙槽骨缺损模型中均能有效促进骨再生。有趣的是，左旋原纤维诱导整合素依赖的成骨分化，进而刺激piezo1介导的血管内皮生长因子（VEGF）驱动的血管生成。因此，这些发现为在下一代再生治疗中利用PDLSCs提供了蓝图。

{"title":"Supramolecular helicity dependent osteogenesis and angiogenesis crosstalk of periodontal ligament stem cell","authors":"Zhuohang Deng , Meijun Li , Yifan Wang , Wenjing Li , Zijian Gong , Peiwen Liao , Shengzhen Luo , Minghua Liu , Xuliang Deng","doi":"10.1016/j.bioactmat.2025.12.057","DOIUrl":"10.1016/j.bioactmat.2025.12.057","url":null,"abstract":"<div><div>The two pillars supporting effective tissue regeneration are multipotent stem cells and matrix materials that direct differentiation. The chirality of the extracellular matrix is a key structural characteristic that affects stem cell fate. However, little is known about the effects of either molecular chirality or supramolecular helicity on the differentiation of periodontal ligament stem cells (PDLSCs), a safe and easily accessible stem cell source. Here, we constructed fibrils through the co-assembly of chiral amino acid derivative enantiomers (<em>l</em>/<em>d</em>-GC18) and a bridging pyrazine molecule. The helicity of the fibrils depends on both the molecular chirality of the amino acid and the stoichiometric ratio of the two components. Our results showed that molecular chirality and supramolecular helicity can act synergistically, with the left-handed fibrils assembled from <em>l</em>-GC18 and pyrazine promoting osteogenic differentiation of PDLSCs <em>in vivo</em>. Moreover, the chiral fibrils effectively promoted bone regeneration in both the calvarial and alveolar bone defect models. Interestingly, it was observed that left-handed fibrils induced integrin-dependent osteogenic differentiation, which in turn stimulated Piezo1-mediated, Vascular Endothelial Growth Factor (VEGF)-driven angiogenesis. These findings thus provide a blueprint for harnessing PDLSCs in next-generation regenerative therapeutics.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 450-462"},"PeriodicalIF":18.0,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881766","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}

引用次数: 0

Injectable living hydrogel as engineered biotherapeutic to promote tooth-extraction wound healing and alveolar bone regeneration 可注射活水凝胶作为工程生物疗法促进拔牙伤口愈合和牙槽骨再生

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-02 DOI: 10.1016/j.bioactmat.2025.12.051

Jingmei Guo , Wenlong Lei , Boyi Li , Kaifeng Li , Jiyun Li , Zhuoran Wang , He Liu , Cui Huang , Ya Shen

Effective wound healing and functional bone regeneration following tooth extraction remain clinical challenges, underscoring the significant need for multifunctional strategies that address the complex, multistage and translational demands of socket management. Herein, an injectable live biotherapeutic hydrogel was fabricated by integrating probiotic Lactobacillus rhamnosus GG (LGG) and calcium phosphate nanoparticles (CP NPs) into a photopolymerizable poly (ethylene glycol) (PEG) matrix. Upon in situ injection and activation with dental blue light, the hydrogel rapidly forms a conformal, protective and bioactive scaffold to the extraction socket. Therapeutically, LGG probiotics remodel the wound microenvironment through antibacterial and immunomodulatory bioactivities to promote early-stage healing. Simultaneously, LGG can facilitate the release of calcium and phosphate ions from CP NPs, which synergizes with microbe-assisted biomineralization to promote osteogenic differentiation and bone regeneration. In vitro and in vivo validations confirmed that this probiotic-mineral biotherapeutic hydrogel concurrently integrates infection control, immune regulation, and osteoinduction within a single clinically deployable platform, representing not only a transformative strategy for post-extraction socket management but also a paradigm for the development of living biomaterials in dynamic tissue engineering applications.

拔牙后有效的伤口愈合和功能性骨再生仍然是临床挑战，强调了对多功能策略的重要需求，以解决牙槽管理的复杂，多阶段和转化需求。本研究将益生菌鼠李糖乳杆菌GG （LGG）和磷酸钙纳米颗粒（CP NPs）整合到光聚合聚乙二醇（PEG）基质中，制备了一种可注射的活生物治疗水凝胶。在原位注射和牙齿蓝光激活后，水凝胶迅速形成一个适形的、保护性的和生物活性的支架。在治疗上，LGG益生菌通过抗菌和免疫调节生物活性重塑伤口微环境，促进早期愈合。同时，LGG可以促进CP NPs中钙和磷酸盐离子的释放，与微生物辅助的生物矿化协同作用，促进成骨分化和骨再生。体外和体内验证证实，这种益生菌矿物生物治疗水凝胶在一个临床可部署的平台内同时集成了感染控制、免疫调节和骨诱导，不仅代表了拔牙后插槽管理的变革策略，也是动态组织工程应用中活生物材料发展的典范。

{"title":"Injectable living hydrogel as engineered biotherapeutic to promote tooth-extraction wound healing and alveolar bone regeneration","authors":"Jingmei Guo , Wenlong Lei , Boyi Li , Kaifeng Li , Jiyun Li , Zhuoran Wang , He Liu , Cui Huang , Ya Shen","doi":"10.1016/j.bioactmat.2025.12.051","DOIUrl":"10.1016/j.bioactmat.2025.12.051","url":null,"abstract":"<div><div>Effective wound healing and functional bone regeneration following tooth extraction remain clinical challenges, underscoring the significant need for multifunctional strategies that address the complex, multistage and translational demands of socket management. Herein, an injectable live biotherapeutic hydrogel was fabricated by integrating probiotic <em>Lactobacillus rhamnosus</em> GG (LGG) and calcium phosphate nanoparticles (CP NPs) into a photopolymerizable poly (ethylene glycol) (PEG) matrix. Upon in situ injection and activation with dental blue light, the hydrogel rapidly forms a conformal, protective and bioactive scaffold to the extraction socket. Therapeutically, LGG probiotics remodel the wound microenvironment through antibacterial and immunomodulatory bioactivities to promote early-stage healing. Simultaneously, LGG can facilitate the release of calcium and phosphate ions from CP NPs, which synergizes with microbe-assisted biomineralization to promote osteogenic differentiation and bone regeneration. In vitro and in vivo validations confirmed that this probiotic-mineral biotherapeutic hydrogel concurrently integrates infection control, immune regulation, and osteoinduction within a single clinically deployable platform, representing not only a transformative strategy for post-extraction socket management but also a paradigm for the development of living biomaterials in dynamic tissue engineering applications.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"59 ","pages":"Pages 355-369"},"PeriodicalIF":18.0,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881688","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}

引用次数: 0

Antifreezing hydrogels for biomedical applications from design strategies to emerging multifunctionality 从设计策略到新兴的多功能生物医学应用的防冻水凝胶

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-02 DOI: 10.1016/j.bioactmat.2025.12.053

Jiang Wu , Lijin Wang , Manhui Zheng , Jie Xu , Zixuan Gong , Boxuan Wu , Huacheng He , Jie Zheng

Antifreezing hydrogels are gaining increasing attention as promising materials for biomedical applications in subzero environments, including cryopreservation, cold-adaptive bioelectronics, wearable sensing, and tissue engineering. Despite recent progress, this is still a relatively underexplored research area, with many fundamental and translational challenges remaining. However, the unique ability of antifreezing hydrogels to sustain flexibility, conductivity, and biological compatibility under freezing conditions underscores their immense potential for future biomedical and engineering innovations. This review provides a targeted overview of the design principles, antifreezing mechanisms, and application-specific adaptations of antifreezing hydrogels. We begin by summarizing fundamental antifreezing strategies, including the incorporation of cryoprotective agents, polymer network engineering, crosslinking architectures, and supramolecular self-healing designs. Particular emphasis is placed on recent advances in hydrogels with integrated strain-sensing, temperature-responsiveness, and multifunctional biosensing capabilities under extreme cold conditions. We then examine cryopreservation-oriented hydrogels, highlighting their ability to suppress ice nucleation, minimize intracellular ice formation, and preserve biological function. The review also explores hydrogel-based cold-adaptive bioelectronics, including low-temperature wearable sensors, flexible circuits, and self-powered interfaces. Finally, we discuss key considerations for clinical translation, such as biocompatibility, degradability, and long-term stability. By linking molecular design to macroscopic performance, this review aims to establish a forward-looking framework for antifreezing hydrogel development across biomedical, environmental, and soft robotic domains.

抗冻水凝胶作为低温环境下生物医学应用的有前途的材料，越来越受到人们的关注，包括低温保存、冷适应生物电子学、可穿戴传感和组织工程。尽管最近取得了进展，但这仍然是一个相对未被充分探索的研究领域，仍然存在许多基础和转化方面的挑战。然而，抗冻水凝胶在冷冻条件下保持柔韧性、导电性和生物相容性的独特能力强调了它们在未来生物医学和工程创新方面的巨大潜力。本文综述了抗冻水凝胶的设计原理、抗冻机理以及抗冻水凝胶的特殊应用。我们首先总结了基本的抗冻策略，包括低温保护剂的结合、聚合物网络工程、交联结构和超分子自愈设计。特别强调了在极端寒冷条件下具有综合菌株传感、温度响应和多功能生物传感能力的水凝胶的最新进展。然后，我们研究了面向低温保存的水凝胶，强调了它们抑制冰核、减少细胞内冰形成和保持生物功能的能力。该综述还探讨了基于水凝胶的冷适应生物电子学，包括低温可穿戴传感器、柔性电路和自供电接口。最后，我们讨论了临床翻译的关键考虑因素，如生物相容性、可降解性和长期稳定性。通过将分子设计与宏观性能联系起来，本文旨在为抗冻水凝胶在生物医学、环境和软机器人领域的发展建立一个前瞻性框架。

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引用次数: 0

Synergistic mitochondrial homeostasis regulation and cholinergic circuits reconstruction via a one-step synthesized multifunctional hydrogel facilitates spinal cord injury repair 一步合成多功能水凝胶协同线粒体稳态调节和胆碱能回路重建促进脊髓损伤修复

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-02 DOI: 10.1016/j.bioactmat.2025.12.009

Yiqian Luo , Pan Jiang , Daoqiang Huang , Hong Li , Jiale He , Ruoqi Shen , Yunheng Jiang , Limin Rong , Bin Liu

Neural Stem Cells (NSCs) possess significant potential to form new neural networks. However, following spinal cord injury (SCI), mitochondrial dysfunction leads to the excessive accumulation of reactive oxygen species (ROS), which severely impairs the neuronal differentiation of endogenous NSCs and thus hinders neural regeneration. Here, we report a multifunctional hydrogel, Poly(LA-Cho)/SS31 (PLCS), synthesized in one step using lipoic acid (LA), choline bicarbonate, and elamipretide (SS31). PLCS hydrogel exhibits injectability, self-healing ability, tissue adhesion, and sequential drug release. Initially, SS31 is released preferentially to scavenge mitochondrial ROS and alleviate mitochondrial dysfunction. Subsequently, LA is continuously to scavenge ROS. Notably, PLCS hydrogel not only promotes NSCs differentiation into cholinergic neurons but also increases acetyl-CoA levels and supplies choline, offering necessary substrates for acetylcholine synthesis in newly formed cholinergic neurons to support their functional maturation. The PLCS hydrogel achieves robust nerve regeneration and significantly improves motor, sensory, and bladder functions in rat models of SCI. RNA sequencing suggests the PI3K-Akt pathway may contribute to spinal cord repair. This one-step synthesis method without catalysts and organic solvents can effectively integrate physical and biological functions of hydrogel, through simple mixing, offering a highly promising strategy for the clinical translation of SCI treatment and other central nervous system injuries.

神经干细胞（NSCs）具有形成新的神经网络的巨大潜力。然而，脊髓损伤（SCI）后，线粒体功能障碍导致活性氧（ROS）过度积累，严重损害内源性NSCs的神经元分化，从而阻碍神经再生。在这里，我们报道了一种多功能水凝胶Poly(LA- cho)/SS31 (PLCS)，它是用硫辛酸（LA）、碳酸氢钠胆碱和埃拉米普肽（SS31）一步合成的。PLCS水凝胶具有可注射性、自愈性、组织黏附性和药物顺序释放性。最初，优先释放SS31清除线粒体ROS，缓解线粒体功能障碍。随后，LA不断清除ROS。值得注意的是，PLCS水凝胶不仅能促进NSCs向胆碱能神经元分化，还能提高乙酰辅酶a水平并提供胆碱，为新形成的胆碱能神经元合成乙酰胆碱提供必要的底物，支持其功能成熟。在脊髓损伤大鼠模型中，PLCS水凝胶实现了强大的神经再生，并显著改善了运动、感觉和膀胱功能。RNA测序表明PI3K-Akt通路可能参与脊髓修复。这种无需催化剂和有机溶剂的一步合成方法，通过简单的混合，可以有效地整合水凝胶的物理和生物功能，为脊髓损伤治疗和其他中枢神经系统损伤的临床翻译提供了一种非常有前景的策略。

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引用次数: 0

LRP-1/CD44-targeted regorafenib nano-delivery system leveraging anti-angiogenesis and synergistic cytotoxicity against peritoneal metastasis of colorectal cancer 靶向LRP-1/ cd44的瑞非尼纳米递送系统抗血管生成和协同细胞毒性对抗结直肠癌腹膜转移

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-02 DOI: 10.1016/j.bioactmat.2025.12.015

Yutong Qian , Meng Wang , Yicong Li , Mei Zhu , Meng Pan , Xicheng Li , Wen Chen , Yujia Wei , Ran Li , Danrong Hu , Zhiyong Qian

Peritoneal metastasis of colorectal cancer (PM-CRC) represents a major therapeutic challenge in advanced disease, where aberrant tumor vasculature contributes to poor prognosis. To address the pharmacological limitations of regorafenib (REG), this study developed a dual-receptor-targeted nanoplatform (REG@LFHA NPs) that leverages the characteristic overexpression of LRP-1 and CD44 receptors in the colorectal cancer tumor microenvironment. The nanoplatform was engineered through nanoprecipitation and electrostatic self-assembly, incorporating lactoferrin for LRP-1 targeting and hyaluronic acid for CD44 recognition. REG@LFHA NPs exert multifaceted antitumor effects through three coordinated mechanisms: potent suppression of tumor vasculature through VEGF-VEGFR pathway blockade, effectively disrupting blood and oxygen supply to induce tumor necrosis; direct tumor cytotoxicity via REG-mediated apoptosis and cell cycle arrest; and immune microenvironment remodeling through macrophage repolarization from pro-tumor M2 to antitumor M1 phenotypes. In PM-CRC models, REG@LFHA NPs demonstrated significantly enhanced tumor accumulation and therapeutic efficacy compared to free REG. Furthermore, the nanoplatform showed remarkable synergy with oxaliplatin, the first-line chemotherapeutic agent for PM-CRC, producing superior treatment outcomes through complementary mechanisms of action. This study not only establishes REG@LFHA NPs as an effective dual-targeting nanomedicine but also demonstrates their strong potential for clinical translation, particularly in combination with standard chemotherapy regimens for advanced peritoneal metastatic colorectal cancer.

结直肠癌腹膜转移（PM-CRC）是晚期疾病的主要治疗挑战，其中肿瘤血管异常导致预后不良。为了解决regafenib （REG）的药理学局限性，本研究开发了一种双受体靶向纳米平台（REG@LFHA NPs），该平台利用了结直肠癌肿瘤微环境中LRP-1和CD44受体的特特性过表达。该纳米平台通过纳米沉淀和静电自组装设计，结合乳铁蛋白靶向LRP-1和透明质酸用于CD44识别。REG@LFHA NPs通过三种协同机制发挥多方面的抗肿瘤作用：通过VEGF-VEGFR通路阻断有效抑制肿瘤血管，有效破坏血液和氧气供应，诱导肿瘤坏死；通过reg介导的细胞凋亡和细胞周期阻滞直接产生肿瘤细胞毒性；通过巨噬细胞从促肿瘤M2表型到抗肿瘤M1表型的再极化来重塑免疫微环境。在PM-CRC模型中，与游离REG相比，REG@LFHA NPs显著增强了肿瘤积累和治疗效果。此外，纳米平台与奥沙利铂（PM-CRC的一线化疗药物）表现出显著的协同作用，通过互补的作用机制产生更好的治疗效果。这项研究不仅确立了REG@LFHA NPs作为一种有效的双靶向纳米药物，而且还证明了它们在临床转化方面的强大潜力，特别是在与晚期腹膜转移性结直肠癌的标准化疗方案联合使用时。

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引用次数: 0

Construction, evaluation, and applications of renal barrier-on-a-chip system 肾屏障芯片系统的构建、评价与应用

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2026-01-02 DOI: 10.1016/j.bioactmat.2025.12.032

Tuya Naren , Weikang Lv , Abdellah Aazmi , Yujun Wang , Haoran Yu , Jie Ying Lee , Huixiang Yang , Mengfei Yu , Xiuxiu Jiang , Huayong Yang , Liang Ma

Organ-on-a-chip (OoC) technology offers a transformative approach to modeling the human renal barrier, overcoming limitations of traditional animal and two-dimensional cell models. This review systematically outlines the construction and evaluation of renal barrier biochips, focusing on the glomerular filtration barrier (GFB), tubular reabsorption barrier (TRB), and collecting duct regulatory barrier (CDRB). OoC platforms integrate biomimetic materials, simulate dynamic microenvironments, and use multicellular co-culture strategies. This enables them to closely replicate the structural and functional characteristics of renal barriers. Key evaluation metrics—including structural biomimicry, barrier integrity, and active transport functions—are discussed to validate model performance. The technology demonstrates significant potential in drug nephrotoxicity prediction, disease mechanism investigation, and regenerative medicine. Despite challenges in material properties and long-term functional maintenance, ongoing advancements in OoC design and integration are poised to enhance its application in precision medicine and kidney disease research.

器官芯片（OoC）技术为人类肾脏屏障建模提供了一种变革性的方法，克服了传统动物和二维细胞模型的局限性。本文系统地综述了肾屏障生物芯片的构建和评价，重点介绍了肾小球滤过屏障（GFB）、小管重吸收屏障（TRB）和收集管调节屏障（CDRB）。OoC平台集成了仿生材料，模拟动态微环境，并采用多细胞共培养策略。这使他们能够紧密地复制肾屏障的结构和功能特征。关键的评估指标——包括结构仿生学、屏障完整性和主动运输功能——被讨论来验证模型的性能。该技术在药物肾毒性预测、疾病机制研究和再生医学方面具有重要的应用潜力。尽管在材料性能和长期功能维护方面存在挑战，OoC设计和集成的持续进步将增强其在精准医学和肾脏疾病研究中的应用。

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