Biomaterials最新文献_第5页

Microenvironment-engineered hydrogels drive osteo-angiogenic coupling to accelerate osteoporotic bone regeneration 微环境工程水凝胶驱动骨血管生成耦合，加速骨质疏松的骨再生

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-02 DOI: 10.1016/j.biomaterials.2025.123966

Ruideng Wang , Xi He , Jinwu Bai , Shilong Su , Haifeng Liu , Fang Zhou

Osteoporotic bone defects repair remians significant clinical challenges, characterized by impaired osteogenic differentiation and dysregulated angiogenesis within a microenvironment of oxidative stress and chronic inflammation. Modulating this pathological microenvironment to create favorable conditions is a pivotal strategy for treating osteoporotic bone defects. In this study, we developed a multifunctional composite hydrogel (SMm) through photo-crosslinking, incorporating Metformin (Met) and magnesium oxide nanoparticles (MgO), to promote osteoporotic bone regeneration. The SMm hydrogel demonstrated optimal physicochemical characteristics and excellent biocompatibility in vitro. Through controlled release of Mg²⁺ ions and Met, the SMm hydrogel exhibited dual bioactivity: (1) robust osteogenic and angiogenic capacity, as evidenced by upregulation of key markers like Col 1, Runx-2 and VEGF, and (2) potent antioxidant and anti-inflammatory effects, effectively scavenging reactive oxygen species (ROS) and suppressing pro-inflammatory cytokines. Notably, under simulated osteoporotic conditions, SMm hydrogel significantly enhanced the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), overcoming the inhibitory microenvironment. In vivo validation using an osteoporotic bone defect model further confirmed the therapeutic efficacy of SMm hydrogel, with micro-CT scans revealing increased new bone formation in the defect area. In summary, this study establishes SMm hydrogel as a promising biomaterial for osteoporotic bone regeneration, leveraging synergistic ion therapy and metabolic modulation to address pathological barriers.

在氧化应激和慢性炎症的微环境中，骨质疏松性骨缺损的修复仍然是一个重大的临床挑战，其特征是成骨分化受损和血管生成失调。调节这种病理微环境以创造有利条件是治疗骨质疏松性骨缺陷的关键策略。在这项研究中，我们通过光交联开发了一种多功能复合水凝胶（SMm），加入二甲双胍（Met）和氧化镁纳米颗粒（MgO），以促进骨质疏松症的骨再生。该水凝胶具有良好的理化特性和良好的体外生物相容性。通过控制Mg2+离子和Met的释放，SMm水凝胶表现出双重生物活性：(1)强大的成骨和血管生成能力，如上调Col 1、Runx-2和VEGF等关键标志物；(2)强大的抗氧化和抗炎作用，有效清除活性氧（ROS）和抑制促炎细胞因子。值得注意的是，在模拟骨质疏松条件下，SMm水凝胶明显增强骨髓间充质干细胞（BMSCs）的成骨分化，克服了抑制微环境。使用骨质疏松性骨缺损模型的体内验证进一步证实了SMm水凝胶的治疗效果，微ct扫描显示缺损区域新骨形成增加。综上所述，本研究确定了SMm水凝胶作为一种有前景的骨质疏松性骨再生生物材料，利用协同离子治疗和代谢调节来解决病理障碍。

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引用次数: 0

Harnessing the death switch: Empowering cancer therapy by modulating the apoptosis-pyroptosis transition 利用死亡开关：通过调节细胞凋亡-焦亡转变增强癌症治疗。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-01 DOI: 10.1016/j.biomaterials.2025.123973

Yan Chen , Jie Wang , Quan Dai , Peng Chen , Haiqing Wang , Ruolan Li , Yanru Gu , Han Liu , Hongtao Xiao , Shugang Qin , Yuying Li , Hongwei Zhang , Qiuju Wang

Overcoming therapeutic resistance mediated by apoptosis evasion represents a critical challenge in cancer treatment. Pyroptosis, an inflammatory form of regulated cell death, provides a promising alternative approach capable of stimulating robust anti-tumor immunity and converting immunologically inert ("cold") tumors into immunologically active ("hot") microenvironments. Importantly, these cell death pathways are not isolated but are interconnected through dynamic molecular switches that determine cellular fate. This review systematically examines the intricate molecular crosstalk between cell death modalities, with particular emphasis on the regulatory roles of the caspase-3/GSDME and caspase-8/GSDMD axes. Current evidence demonstrates that caspase family members, primarily associated with apoptosis, can selectively cleave gasdermin proteins, facilitating a transition from non-inflammatory apoptotic signaling to inflammatory pyroptotic events. We further analyze how inflammasomes, post-translational modifications, and the STING–NF–κB pathway precisely regulate this transition. Through integrated bioinformatic analysis, we identified novel hub genes (e.g., PRKAR1A, PPP2CA, FOSL2) and microRNA networks at the apoptosis-pyroptosis interface, providing novel insights and potential therapeutic targets. Exploiting this 'death switch' offers a novel therapeutic framework through three principal strategies: (1) inducing pyroptosis to eliminate apoptosis-resistant cells, (2) utilizing pyroptosis-induced inflammation to enhance immune checkpoint inhibitor efficacy, and (3) developing targeted therapeutics that directly modulate these switch molecules. Although controlling pyroptosis-associated inflammation remains challenging, understanding and manipulating the apoptosis-to-pyroptosis transition provides an innovative approach to overcome drug resistance and develop more effective cancer treatments.

克服由细胞凋亡逃避介导的治疗耐药是癌症治疗的一个关键挑战。焦亡是一种受调节的细胞死亡的炎症形式，它提供了一种有希望的替代方法，能够刺激强大的抗肿瘤免疫，并将免疫惰性（“冷”）肿瘤转化为免疫活性（“热”）微环境。重要的是，这些细胞死亡途径不是孤立的，而是通过决定细胞命运的动态分子开关相互连接的。这篇综述系统地研究了细胞死亡模式之间复杂的分子串扰，特别强调了caspase-3/GSDME和caspase-8/GSDMD轴的调节作用。目前的证据表明，caspase家族成员，主要与细胞凋亡相关，可以选择性地切割气皮蛋白，促进从非炎性凋亡信号传导到炎性焦亡事件的转变。我们进一步分析了炎症小体、翻译后修饰和STING-NF-κB通路如何精确调节这一转变。通过综合生物信息学分析，我们确定了新的中枢基因（如PRKAR1A， PPP2CA, FOSL2）和凋亡-焦凋亡界面的microRNA网络，提供了新的见解和潜在的治疗靶点。利用这种“死亡开关”通过三个主要策略提供了一种新的治疗框架：(1)诱导热亡以消除凋亡抵抗细胞，(2)利用热亡诱导的炎症来增强免疫检查点抑制剂的功效，(3)开发直接调节这些开关分子的靶向治疗方法。尽管控制与焦亡相关的炎症仍然具有挑战性，但理解和操纵细胞凋亡到焦亡的转变为克服耐药性和开发更有效的癌症治疗提供了一种创新的方法。

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引用次数: 0

Carrier-free nanoassembly with dual antioxidant and anti-inflammatory activities camouflaged by melanoma cell membrane for tau-targeted therapy of Alzheimer's disease 具有双重抗氧化和抗炎活性的无载体纳米组装被黑色素瘤细胞膜伪装用于tau靶向治疗阿尔茨海默病

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-31 DOI: 10.1016/j.biomaterials.2025.123970

Rui Xue , Fengyu Wang , Beibei Zhang , Jin Wu , Ningnannan Zhang , Chunyang Sun

Targeting phosphorylated tau (p-tau) across the blood–brain barrier (BBB) represents a critical prerequisite for attenuating tau pathology and disease progression in Alzheimer's disease (AD) by alleviating oxidative stress and neuroinflammation. To address this challenge, we developed a novel carrier-free selenium-based nanoassembly stabilized by hydroxyl-rich fingolimod (FTY720), a sphingosine analogue. Following camouflaging with melanoma cell membranes and further functionalizing with T807, the resulting nanocomposite (FSMT) demonstrated robust capacity for BBB crossing and target p-tau both in vitro and in vivo. Additionally, FTY720 and nano-selenium exert remarkable antioxidant and anti-inflammatory effects by modulating the GSK-3β and NF-κB signaling pathways, respectively, thereby attenuating tau hyperphosphorylation and preventing neuronal cell death. In an okadaic acid-induced AD mouse model, the FSMT treatment not only significantly ameliorated oxidative stress and neuroinflammation, but also improved spatial learning and memory impairments. The reduction in abnormal tau aggregation following treatment was confirmed by PET-CT imaging. Overall, this p-tau-targeted biomimetic nanocomposite demonstrated excellent biocompatibility and therapeutic efficacy, presenting a translatable strategy for treating AD and other neurological disorders through analogous mechanisms.

通过血脑屏障（BBB）靶向磷酸化tau （p-tau）是通过减轻氧化应激和神经炎症来减轻阿尔茨海默病（AD）中tau病理和疾病进展的关键先决条件。为了解决这一挑战，我们开发了一种新的无载体硒基纳米组件，由富含羟基的芬戈莫德（FTY720）稳定，这是一种鞘氨醇类似物。经过黑色素瘤细胞膜的伪装和T807的进一步功能化，得到的纳米复合材料（FSMT）在体外和体内都显示出强大的血脑屏障穿越能力和靶向p-tau的能力。此外，FTY720和纳米硒分别通过调节GSK-3β和NF-κB信号通路发挥显著的抗氧化和抗炎作用，从而减轻tau过度磷酸化，防止神经元细胞死亡。在冈田酸诱导的AD小鼠模型中，FSMT治疗不仅能显著改善氧化应激和神经炎症，还能改善空间学习和记忆障碍。治疗后异常tau聚集的减少通过PET-CT成像证实。总的来说，这种靶向p-tau的仿生纳米复合材料表现出良好的生物相容性和治疗效果，通过类似的机制为治疗AD和其他神经系统疾病提供了可翻译的策略。

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引用次数: 0

An innate immunity-reprogramming hydrogel nips postoperative adhesions in the bud via transforming pathological healing into physiological recovery 先天免疫重编程水凝胶通过将病理愈合转化为生理恢复，将术后粘连扼杀在萌芽状态

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-31 DOI: 10.1016/j.biomaterials.2025.123972

Yinqi Chen , Jiafeng Wang , Yechun Wang , Zimeng Liu , Jiajia Ying , Xuefei Zhou , Tianhua Zhou , Haiping Jiang , Xiangrui Liu , Quan Zhou

Postoperative adhesions are frequent and challenging complication lacking effective prevention. Evidence indicates that innate immune responses triggered by surgical trauma critically influence whether normal tissue repair progresses to pathological adhesions, highlighting early inflammatory responders as key intervention targets. Here, we successfully transformed natural hyaluronic acid (HA) into a potent innate inflammation modulator through a one-step sulfoxide-conjugation strategy. The resultant sulfoxide-conjugated HA (SOHA) demonstrated near-complete prevention of adhesion formation across multiple clinically relevant animal models, including those for secondary injury, long-term abdominal adhesions, and pericardial–pleural adhesions. Mechanistic investigations reveal that, unlike traditional physical barriers that primarily inhibit the late-stage adhesion of activated fibroblasts, SOHA addresses postoperative adhesions at their inception by reprogramming early innate inflammatory responses. It shifts the neutrophil cell death mode from acute, pro-inflammatory NETosis to more regulated, immunologically silent apoptotic process. Furthermore, it selectively restrains the early accumulation of large peritoneal macrophages (LPMs) in damaged tissues, redirecting them towards a reparative M2-like phenotype through the efferocytic clearance of apoptotic neutrophils, thereby promoting their timely involvement during the resolution phase of inflammation. This dual regulation of innate immunity effectively interrupts the postoperative inflammatory cascade and subsequent fibrotic progression, thus effectively shifting the pathological tissue repair into physiological healing.

术后粘连是常见且具有挑战性的并发症，缺乏有效的预防。有证据表明，手术创伤引发的先天免疫反应对正常组织修复是否发展为病理性粘连具有重要影响，因此早期炎症反应者是关键的干预目标。在这里，我们通过一步亚砜偶联策略成功地将天然透明质酸（HA）转化为一种有效的先天炎症调节剂。由此产生的亚砜偶联HA （SOHA）在多个临床相关动物模型中几乎完全预防了粘连的形成，包括继发性损伤、长期腹腔粘连和心包-胸膜粘连。机制研究表明，与传统的物理屏障主要抑制活化成纤维细胞的晚期粘连不同，SOHA通过重新编程早期先天炎症反应，在术后粘连开始时解决粘连问题。它将中性粒细胞死亡模式从急性、促炎的NETosis转变为更受调节的、免疫沉默的凋亡过程。此外，它选择性地抑制大腹膜巨噬细胞（lpm）在受损组织中的早期积累，通过对凋亡中性粒细胞的efferocytic清除，将它们定向到修复性m2样表型，从而促进它们在炎症消退阶段的及时参与。这种先天免疫的双重调控有效地阻断了术后炎症级联和随后的纤维化进展，从而有效地将病理性组织修复转变为生理性愈合。

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引用次数: 0

Renal-clearable organic NIR-II dye cluster for non-invasive ureteral imaging 肾脏可清除的有机NIR-II染料簇用于无创输尿管成像

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-30 DOI: 10.1016/j.biomaterials.2025.123951

Shengjie Ma , Zimu Yuan , Chenlong Yu , Bin Sun , Ruibo Tang , Ding Zhou , Shoujun Zhu , Quan Wang

Intraoperative ureter visualization is essential in colorectal cancer (CRC) surgery, but current modalities are limited by invasiveness, poor photostability, and insufficient spatial resolution. Second near-infrared (NIR-II) fluorescence imaging provides a non-invasive approach with improved tissue penetration and spatial resolution. By modulating the aggregation behavior of NIR-II dyes, intravenous administration followed by renal metabolism enables real-time, high-resolution ureteral visualization. In this study, we prepared a series of donor–acceptor–donor-based NIR-II probes through a one-pot process where dye synthesis/PEGylation and free PEG assembly occur concurrently. The IR-FEP₁₀₀₀ cluster absorbs/emits maximally at 784/1025 nm in PBS and exhibits high photobleaching resistance due to its unique structural rigidity. Importantly, the IR-FEP₁₀₀₀ cluster exhibited renal excretion and enabled superior ureteral imaging performance with excellent biocompatibility, high resolution, and a prolonged imaging window. Furthermore, the IR-FEP₁₀₀₀ cluster enabled non-invasive, effective imaging diagnosis in scenarios of accidental ureteral transection, ligation, and clamping. Moreover, the IR-FEP₁₀₀₀ cluster combined with CO-1080 and Er-NPs enables multiplexed NIR-II imaging-guided surgery. High-contrast three-channel intraoperative imaging of the CRC peritoneal metastases, the ureters, and the intestines was provided. Multiplex NIR-II imaging enables precise tumor resection while protecting vital organs from intraoperative injury. These findings highlight that the IR-FEP₁₀₀₀ cluster exhibits advantages in non-invasive, long-duration, and high-resolution ureteral imaging with broad prospects in complex surgical scenarios.

术中输尿管可视化在结直肠癌（CRC）手术中是必不可少的，但目前的方式受到侵入性、光稳定性差和空间分辨率不足的限制。第二种近红外（NIR-II）荧光成像提供了非侵入性方法，提高了组织穿透性和空间分辨率。通过调节NIR-II染料的聚集行为，静脉给药后的肾脏代谢可以实现实时、高分辨率的输尿管可视化。在这项研究中，我们通过一锅工艺制备了一系列基于供体-受体-供体的NIR-II探针，其中染料合成/聚乙二醇化和游离聚乙二醇组装同时进行。IR-FEP1000簇在PBS中在784/1025 nm处吸收/发射最大，由于其独特的结构刚性，具有较高的抗光漂白性能。重要的是，IR-FEP1000簇显示肾脏排泄，具有优异的生物相容性，高分辨率和延长的成像窗口，具有优越的输尿管成像性能。此外，IR-FEP1000集群能够在意外输尿管横断、结扎和夹紧的情况下进行无创、有效的成像诊断。此外，IR-FEP1000簇与CO-1080和Er-NPs结合可以实现多路NIR-II成像引导手术。术中提供了结直肠癌腹膜转移灶、输尿管和肠道的高对比度三通道成像。多重NIR-II成像可以精确切除肿瘤，同时保护重要器官免受术中损伤。这些发现表明IR-FEP1000簇在无创、长时间、高分辨率输尿管成像方面具有优势，在复杂手术场景中具有广阔的应用前景。

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引用次数: 0

Kudzu root-derived carbon dots modulate gut microbiota and metabolites for pan-organ targeted macrophage polarization in synergistic diabetes therapy 葛根碳点调节肠道菌群和代谢物，协同治疗糖尿病中泛器官靶向巨噬细胞极化。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-29 DOI: 10.1016/j.biomaterials.2025.123967

Jianing Yi , Yuanyu Tang , Yilin Chen , Liang Chen , Dongxue Geng , Luyao Liu , Jie Yu , Lianhong Zou , Jie Zeng , Minhuan Lan , Wenjie Gao , Ming Gao

Type 2 diabetes is a systemic disorder characterized by metabolic dysfunction and chronic inflammation, yet strategies that address both aspects remain limited. Here, we present kudzu root–derived carbon dots (KRCDs) as a natural nanomaterial that reprograms the gut microbiota-metabolite-immune axis to restore systemic homeostasis. KRCDs exhibit nanoscale crystallinity, abundant O/N functional groups, and strong antioxidant activity. In high-fat diet/streptozotocin-induced diabetic mice, KRCDs significantly lowered fasting glucose, improved glucose tolerance and insulin sensitivity, corrected lipid profiles, and reduced hepatic steatosis without detectable toxicity. Multi-omics analyses revealed increased microbial diversity, enrichment of beneficial genera such as Anaerostipes, and remodeling of fecal metabolites with a marked rise in indole-3-carboxaldehyde (I3A). This metabolite correlated with enhanced M2-like macrophage polarization across adipose tissue, intestine, kidney, liver, and pancreas, as confirmed by flow cytometry and immunofluorescence. Fecal microbiota transplantation from KRCDs-treated donors reproduced both the metabolic improvements and the organ-wide M2 polarization, confirming a microbiota-dependent mechanism. By establishing a gut microbiota–metabolite–macrophage polarization pathway, KRCDs act as safe, plant-based nanoplatforms that simultaneously correct metabolic and immune imbalance, offering a promising strategy for multi-target intervention in diabetes.

2型糖尿病是一种以代谢功能障碍和慢性炎症为特征的全身性疾病，但针对这两方面的策略仍然有限。在这里，我们提出了葛根衍生的碳点（KRCDs）作为一种天然纳米材料，可以重新编程肠道微生物群-代谢物-免疫轴，以恢复系统稳态。KRCDs具有纳米级结晶度、丰富的O/N官能团和较强的抗氧化活性。在高脂肪饮食/链脲佐菌素诱导的糖尿病小鼠中，KRCDs显著降低了空腹血糖，改善了葡萄糖耐量和胰岛素敏感性，纠正了脂质谱，减少了肝脏脂肪变性，而没有可检测到的毒性。多组学分析显示，微生物多样性增加，厌氧菌等有益菌丰富，粪便代谢物重塑，吲哚-3-甲醛（I3A）显著增加。流式细胞术和免疫荧光证实，这种代谢物与脂肪组织、肠道、肾脏、肝脏和胰腺中m2样巨噬细胞极化增强相关。来自krcd治疗供体的粪便微生物群移植重现了代谢改善和全器官M2极化，证实了微生物群依赖的机制。通过建立肠道微生物-代谢物-巨噬细胞极化通路，KRCDs作为安全的植物纳米平台，同时纠正代谢和免疫失衡，为糖尿病的多靶点干预提供了一种有希望的策略。

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引用次数: 0

Bridging acute-chronic myocardial infarction treatment: Dual-regulating of ROS/fibrosis via microenvironment-responsive release of NO and curcumin 桥接急慢性心肌梗死治疗：通过微环境响应性释放NO和姜黄素对ROS/纤维化的双重调节

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-29 DOI: 10.1016/j.biomaterials.2025.123954

Fang Zhang , Bingbing Zhao , Keqiang Lu , Xueping Zeng , Zikun Wang , Wei Chen , Yunyun Zhou , Juanjuan Peng , Lingzhi Zhao

Oxidative stress and fibrosis are core drivers of post-myocardial infarction dysfunction. Conventional therapies predominantly address either acute oxidative damage or chronic fibrosis, lacking strategies that concurrently target the two interconnected processes. Here, a microenvironment-responsive nanomedicine delivering nitric oxide (NO) and curcumin specifically to the infarcted heart is presented (named C@Si-NM). Constructed from glutathione-sensitive cyclic nitrate-trimethylene carbonate-polyethylene glycol block copolymer micelles crosslinked with silica, the system releases both NO and the encapsulated curcumin upon encountering elevated glutathione levels at the infarction site. In cardiomyocytes, NO suppresses the opening of mitochondrial permeability transition pore, inhibiting the release of reactive oxygen species, while curcumin directly acts as an antioxidant. In fibroblasts, NO inhibits the TGF-β/Smad pathway and curcumin downregulates the production of TGF-β, jointly suppressing fibrosis. The combined nanomedicine C@Si-NM significantly improved cardiac function in a rat model of MI after four weeks of treatment, resulting in an ejection fraction of 74 %. This value approached the normal range of 81 % and was superior to the outcomes observed with NO monotherapy at 62 % or curcumin monotherapy at 63 %. This strategy effectively mitigates both oxidative damage and fibrosis, bridging the gap between acute and chronic therapeutic interventions of myocardial infarction.

氧化应激和纤维化是心肌梗死后功能障碍的核心驱动因素。传统疗法主要针对急性氧化损伤或慢性纤维化，缺乏同时针对这两个相互关联的过程的策略。本文提出了一种微环境响应纳米药物，可将一氧化氮（NO）和姜黄素特异性地递送到梗死心脏（命名为C@Si-NM）。该系统由谷胱甘肽敏感的环硝酸盐-碳酸三亚甲基-聚乙二醇嵌段共聚物胶束与二氧化硅交联而成，当在梗死部位遇到谷胱甘肽水平升高时，该系统会释放NO和被封装的姜黄素。在心肌细胞中，NO抑制线粒体通透性过渡孔的打开，抑制活性氧的释放，而姜黄素则直接起到抗氧化剂的作用。在成纤维细胞中，NO抑制TGF-β/Smad通路，姜黄素下调TGF-β的产生，共同抑制纤维化。联合纳米药物C@Si-NM在治疗四周后显著改善心肌梗死大鼠模型的心功能，导致射血分数达到74%。该值接近81%的正常范围，优于NO单药治疗的62%或姜黄素单药治疗的63%。这一策略有效地减轻了氧化损伤和纤维化，弥合了心肌梗死急性和慢性治疗干预之间的差距。

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引用次数: 0

Engineering bioactive fibrous constructs: Bioprinting stem cell-laden collagen-derived hydrogels with short collagen microfibers 工程生物活性纤维结构：具有短胶原微纤维的生物打印满载干细胞的胶原衍生水凝胶。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-29 DOI: 10.1016/j.biomaterials.2025.123965

Hongjuan Weng , Monize C. Decarli , Wen Chen , Katrien V. Bernaerts , Lorenzo Moroni

Natural hydrogels (e.g., collagen hydrogels) show good potential in understanding cell-matrix interaction and find application in tissue engineering. However, it remains challenging to bioprint cell-laden natural hydrogels with good printability, shape retention and stability. In this study, non-water-soluble short collagen type I microfibers (COL-I μFiber) were blended with water-soluble methacrylated collagen peptide (COPMA) and xanthan gum (XG), forming an interpenetrated network, and bioprinted into stable natural-derived COPMA-μFiber-XG constructs, followed by in situ stem cell proliferation and differentiation. First, to enhance the printability and the mechanical properties of COPMA, a COPMA-μFiber-XG bioink was developed, featuring rapid UV-curing and self-healing properties. The encapsulated human mesenchymal stem cells (hMSCs) spread along the COL-I μFibers in the bioprinted constructs, with increased metabolic activity and production of extracellular matrix and bioactive proteins (COL-I and scleraxis) in 28 days. The internal biophysical and biochemical signals provided by COL-I μFibers and the fibrous COPMA matrix synergistically interacted with exogenous biochemical signals (e.g., transforming growth factor-beta 3) to further promote stem cell differentiation. Overall, bioprinted fibrous COPMA-μFiber-XG constructs are biocompatible and bioactive matrices to support hMSCs proliferation and differentiation.

天然水凝胶（如胶原蛋白水凝胶）在理解细胞-基质相互作用方面具有良好的潜力，并在组织工程中得到应用。然而，具有良好的可打印性、形状保持性和稳定性的生物打印细胞负载天然水凝胶仍然是一个挑战。本研究将非水溶性短型胶原I型微纤维（COL-I μFiber）与水溶性甲基丙烯酸化胶原肽（COPMA）和黄原胶（XG）共混，形成互渗透网络，并生物打印成稳定的天然来源的COPMA-μFiber-XG结构，随后进行原位干细胞增殖和分化。首先，为了提高COPMA的打印性能和力学性能，研制了一种具有快速紫外固化和自愈性能的COPMA-μFiber-XG生物墨水。包被的人间充质干细胞（hMSCs）在生物打印构建体中沿col - 1 μ纤维扩散，28天内代谢活性增加，细胞外基质和生物活性蛋白（col - 1和sclcleraxis）的产生增加。col - 1 μFibers和纤维状COPMA基质提供的内部生物物理生化信号与外源生化信号（如转化生长因子- β 3）协同作用，进一步促进干细胞分化。总体而言，生物打印纤维COPMA-μFiber-XG构建物具有生物相容性和生物活性，可支持hMSCs的增殖和分化。

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引用次数: 0

Duo-nano exosome encapsulating hydrogel boosts wound healing across xenogenic and allogenic models 双纳米外泌体包封水凝胶促进伤口愈合跨越异种和同种异体模型

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-27 DOI: 10.1016/j.biomaterials.2025.123953

Bibi S. Subhan , Sydney E. Hanson , Dianny Almanzar , Juan F. Cortes Troncoso , Priya Katyal , Jonathan W. Sun , Hao-Wei Shih , Tamara Mestvirishvili , Michael Meleties , Fernando Arias , Andrew Wang , Kelly Ruggles , Igor Dolgalev , Paolo Mita , Jin Kim Montclare , Piul S. Rabbani

Chronic wounds, especially in diabetic patients, pose a significant clinical challenge due to impaired microvasculature and delayed healing. This study presents Exo-Q, a novel thermoresponsive hydrogel formed by co-gelation of engineered Q protein nanofibers with exosomes, a class of vesicular intercellular communication mediators. Exo-Q transitions from a gel to a viscoelastic solution at physiological temperature, enabling localized, topical delivery of exosomes with an initial burst release followed by sustained release. In a diabetic mouse wound model, Exo-Q effectively delivered human bone marrow multipotent stromal cell-derived exosomes directly to the wound bed, where they accumulated in endothelial cells of granulation tissue without detectable systemic distribution. Exosomes produced under stringent and replicable cell culture conditions consistently carried biomacromolecular cargo enriched for miRNAs with validated targets in angiogenesis-associated genes, indicative of their therapeutic potential. Topical application of Exo-Q resulted in extensive neovascularized granulation tissue, significantly accelerating wound closure to levels comparable to non-diabetic wounds. Importantly, the hydrogel’s modular design maintained the functional integrity of Q protein nanofibers and exosomes, demonstrating compatibility with full-thickness human wounds. This platform allows for tailored customization to address critical stages of diabetic wound healing while ensuring efficacy at low dosages, potentially enabling patient-administered treatment. By leveraging advanced biomaterials, Exo-Q advances the therapeutic efficacy of exosome-based interventions for diabetic wounds, offering a localized, non-invasive solution to chronic, non-healing wounds. This innovative hydrogel platform represents a modular therapeutic strategy with significant potential for clinical applications in regenerative medicine.

慢性伤口，特别是糖尿病患者，由于微血管受损和愈合延迟，构成了一个重大的临床挑战。这项研究提出了Exo-Q，一种新型的热响应性水凝胶，由工程Q蛋白纳米纤维与外泌体（一类囊泡细胞间通讯介质）共凝胶形成。Exo-Q在生理温度下从凝胶转变为粘弹性溶液，使外泌体能够在初始爆发释放后持续释放的情况下局部局部递送。在糖尿病小鼠伤口模型中，Exo-Q有效地将人骨髓多能基质细胞衍生的外泌体直接递送到伤口床，在那里它们积聚在肉芽组织的内皮细胞中，没有可检测到的全身分布。在严格和可复制的细胞培养条件下产生的外泌体始终携带富含mirna的生物大分子货物，这些mirna在血管生成相关基因中具有有效的靶标，表明它们具有治疗潜力。外用Exo-Q导致广泛的新生血管化肉芽组织，显著加速伤口愈合，达到与非糖尿病伤口相当的水平。重要的是，水凝胶的模块化设计保持了Q蛋白纳米纤维和外泌体的功能完整性，证明了与全层人体伤口的兼容性。该平台允许量身定制，以解决糖尿病伤口愈合的关键阶段，同时确保低剂量的疗效，潜在地实现患者给药治疗。通过利用先进的生物材料，Exo-Q提高了基于外泌体的糖尿病伤口干预的治疗效果，为慢性、不愈合的伤口提供了局部、非侵入性的解决方案。这种创新的水凝胶平台代表了一种模块化治疗策略，在再生医学的临床应用中具有重要的潜力。

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引用次数: 0

Spatiotemporal controlled disintegration enabling injected magnetic hydrogel for percutaneous hepatocellular carcinoma treatment 经皮肝细胞癌的时空可控崩解注射磁性水凝胶治疗

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2025-12-26 DOI: 10.1016/j.biomaterials.2025.123952

Bing Chen , Hanye Xing , Xingyu Liu , Jinlong Hu , Liang Dong , Xu Yan , Yonghong Song , Yang Lu

Disintegrating hydrogels offer the advantages of synergistically enhancing therapeutic efficacy in locoregional percutaneous treatment for early hepatocellular carcinoma, enabling on-demand drug delivery with reduced side effects. However, current disintegration processes suffer from limited precise control and weak tissue penetration. Herein, we constructed an injectable ferrimagnetic hydrogen bonding cross-linked hydrogel (named as FPH) as a locoregional percutaneous agent by integrating ferrimagnetic nanoparticles into a polyvinyl alcohol (PVA) crosslinked network. This hydrogel enables remote magnetothermally triggered disintegration under an alternating magnetic field (AMF), with its disintegration temperature precisely tunable by adjusting the hydrogel's solid content. Under magnetic heating effect, FPH achieved remote “gel to disintegration” behavior at a desired temperature range of around 47 °C, effectively suppressing tumor cells and minimizing harm to normal tissues. By contrast, other commonly used hydrogen-bonded network of gelatin hydrogel disintegrated below body temperature or agarose hydrogel disintegrated over 70 °C. Benefiting from magnetothermal-controlled disintegration, drug-loaded FPH exhibited an increased release efficiency from ∼8 % (without AMF) to ∼45 % (with AMF) within 1 h. Following ultrasound-guided percutaneous delivery, FPH_DOX exhibited synergistic efficacy with magnetic hyperthermia and disintegration-mediated chemotherapy in rabbit liver tumors. Additionally, FPH is fabricated using clinically approved pharmaceutical excipients, ensuring excellent biocompatibility. This strategy inspires the design of spatiotemporally controllable disintegrating hydrogels with limitless tissue penetration depth, and expands their potential in percutaneous hepatocellular carcinoma treatment.

崩解水凝胶在早期肝细胞癌局部经皮治疗中具有协同增强疗效的优势，能够按需给药，减少副作用。然而，目前的崩解过程受到有限的精确控制和弱组织渗透的影响。本文中，我们通过将铁磁纳米颗粒整合到聚乙烯醇（PVA）交联网络中，构建了一种可注射的铁磁氢键交联水凝胶（FPH）作为局部区域透皮剂。这种水凝胶可以在交变磁场（AMF）下实现远程磁热触发分解，通过调节水凝胶的固体含量，可以精确调节其分解温度。在磁加热作用下，FPH在47℃左右的理想温度范围内实现了远程“凝胶到崩解”行为，有效抑制肿瘤细胞，最大限度地减少对正常组织的伤害。相比之下，其他常用的明胶水凝胶的氢键网络在体温以下崩解，琼脂糖水凝胶在70℃以上崩解。受益于磁热控制的崩解，载药FPH在1小时内的释放效率从8%（无AMF）增加到45%（有AMF）。超声引导下经皮给药后，FPHDOX在兔肝肿瘤中表现出与磁热疗和崩解介导的化疗协同作用。此外，FPH是使用临床批准的药物辅料制造的，确保了良好的生物相容性。这一策略启发了具有无限组织穿透深度的时空可控分解水凝胶的设计，并扩大了其在经皮肝细胞癌治疗中的潜力。

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引用次数: 0