Materials Today Bio最新文献_第9页

Active-targeted nano-hemostatic for hemostasis and brain microenvironment optimization in intracerebral hemorrhage therapy 活性靶向纳米止血剂用于脑出血治疗中的止血和脑微环境优化

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2025-12-13 DOI: 10.1016/j.mtbio.2025.102671

Junyan An , Tian Wang , Yihan Wang , Meiyan Sun , Ke Meng , Yixuan Wang , Hang Xu , Daping Ye , Zhilin Liu , Miao Li , Zhaohui Tang

Intracerebral hemorrhage (ICH) is a life-threatening cerebrovascular disorder characterized by rapid hematoma expansion and secondary neurovascular injury, resulting in high mortality and disability. Current hemostatic drugs lack lesion selectivity and fail to stabilize fragile vasculature, leaving patients vulnerable to secondary rebleeding. To address these limitations, we developed ATHEMO (Active-Targeted HEmostasis and brain Microenvironment Optimizer), a peptide-modified nanoplatform designed for targeted hemostasis and sustained neuroprotection. Incorporating a von Willebrand factor (vWF)–binding sequence, ATHEMO precisely homes to ruptured vessels, where it establishes a stable adhesive interface that halts active bleeding and reinforces vascular integrity. Concurrently, the nanocarrier provides controlled release of quercetin, effectively mitigating oxidative stress, promoting M2-type microglial polarization, and preserving blood–brain barrier function. In a murine ICH model, ATHEMO reduced hematoma volume by nearly 70 %, alleviated cerebral edema, improved perfusion, and restored both cognitive and motor functions during long-term recovery. Transcriptomic profiling revealed downregulation of inflammatory cascades and enhancement of synaptic signaling, underscoring ATHEMO's dual hemostatic and neuroprotective effects. These findings demonstrate that combining targeted bleeding control with microenvironment regulation offers a precision nanotherapeutic strategy for ICH, potentially translatable to other non-compressible hemorrhagic conditions.

脑出血是一种危及生命的脑血管疾病，以血肿迅速扩张和继发性神经血管损伤为特征，导致高死亡率和致残率。目前的止血药物缺乏病变选择性，不能稳定脆弱的血管系统，使患者容易发生继发性再出血。为了解决这些限制，我们开发了ATHEMO（主动靶向止血和大脑微环境优化器），这是一种肽修饰的纳米平台，用于靶向止血和持续的神经保护。结合血管性血友病因子（vWF）结合序列，ATHEMO可以精确地附着在破裂的血管上，在那里建立稳定的粘附界面，阻止活动性出血，加强血管完整性。同时，纳米载体提供槲皮素的控释，有效减轻氧化应激，促进m2型小胶质细胞极化，维护血脑屏障功能。在小鼠脑出血模型中，ATHEMO可减少近70%的血肿体积，减轻脑水肿，改善灌注，并在长期恢复过程中恢复认知和运动功能。转录组学分析显示炎症级联反应的下调和突触信号的增强，强调了ATHEMO的双重止血和神经保护作用。这些发现表明，将靶向出血控制与微环境调节相结合，为脑出血提供了一种精确的纳米治疗策略，可能可转化为其他不可压缩性出血疾病。

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引用次数: 0

Co-delivery of panobinostat and siSTAT3 using engineered M1 exosomes to establish a one-two punch therapeutic strategy for glioblastoma recurrence 利用工程化M1外泌体共同递送panobinostat和siSTAT3，建立一种针对胶质母细胞瘤复发的组合式治疗策略

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2025-12-13 DOI: 10.1016/j.mtbio.2025.102680

Xuemeng Liu , Yaotian Hu , Yan Zhang , Chang Liu , Jingwen Wu , Ruiqi Zhao , Zhiyi Xue , Wenjing Zhou , Xiaofei Liu , Hrvoje Miletic , Yongli Gao , Chen Qiu , Jian Wang

Effectively treating recurrent glioblastoma (GB) remains a significant challenge in the clinic. Considering the multifactorial nature of GB progression, a comprehensive therapeutic strategy that directly targets both the tumor cells and its microenvironment is crucial. In this study, we developed an approach using exosomes derived from genetically modified M1 macrophages that encapsulate panobinostat and siSTAT3 to treat recurrent GB. We demonstrate that this innovative system has an innate ability to actively home to tumor cells, leveraging the inflammation-targeting capabilities of M1 macrophage-derived exosomes. These exosomes are pivotal in shifting the balance from M2 macrophages to the more favorable M1 phenotype within the tumor microenvironment. By loading the exosomes with panobinostat, a compound that faces challenges crossing the blood-brain barrier, it can efficiently access and act upon the tumor. Moreover, with the co-delivery of siSTAT3, the exosomes display various functionalities, such as inhibiting GB proliferation and invasion, preventing astrocyte reactivity, and reducing M2 macrophage infiltration. This “one-two punch” approach offers a powerful combined anticancer effect through simultaneously targeting tumor cells and reshaping the tumor microenvironment, which holds considerable promise in curbing GB recurrence and provides hope for more effective future treatments.

有效治疗复发性胶质母细胞瘤（GB）在临床上仍然是一个重大挑战。考虑到GB进展的多因素性质，直接针对肿瘤细胞及其微环境的综合治疗策略至关重要。在这项研究中，我们开发了一种方法，使用基因修饰的M1巨噬细胞衍生的外泌体包封panobinostat和siSTAT3来治疗复发性GB。我们证明，这种创新系统具有一种先天的能力，利用M1巨噬细胞来源的外泌体的炎症靶向能力，主动返回肿瘤细胞。这些外泌体在肿瘤微环境中将M2巨噬细胞的平衡转移到更有利的M1表型中起关键作用。通过将panobinostat（一种面临穿越血脑屏障挑战的化合物）装入外泌体，它可以有效地进入并作用于肿瘤。此外，随着siSTAT3的共递送，外泌体显示出多种功能，如抑制GB增殖和侵袭，防止星形胶质细胞反应性，减少M2巨噬细胞浸润。这种“双管齐下”的方法通过同时靶向肿瘤细胞和重塑肿瘤微环境，提供了强大的联合抗癌效果，在抑制GB复发方面具有相当大的希望，并为未来更有效的治疗提供了希望。

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引用次数: 0

PtTe2-alginate hydrogels for combined photothermal-chemodynamic cancer therapy by inducing cell apoptosis via modulation of TNF-α-related signaling pathways ptte2 -海藻酸盐水凝胶通过调节TNF-α相关信号通路诱导细胞凋亡，用于光热-化学动力联合治疗癌症

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2025-12-13 DOI: 10.1016/j.mtbio.2025.102679

Jiayao Tong , Jiaqi Qin , Jianghao Xing , Huansuo Ren , Peng Cao , Hui Wang , Pengyu Pan , Xianwen Wang , Haowei Xue

Head and neck squamous cell carcinoma ranks as the sixth most common malignant tumor worldwide, with the majority of cases manifesting as oral squamous cell carcinoma (OSCC). The current clinical standard for treating OSCC consists of surgical resection followed by radiotherapy and chemotherapy. This multimodal approach, however, is associated with substantial morbidity, significant perioperative risk, and frequent systemic toxicities that markedly impair quality of life. Therefore, novel, more effective, and safer treatment strategies are urgently needed. Here, PtTe₂ nanorods were synthesized and encapsulated in sodium alginate (ALG) to form a novel injectable hydrogel for the precise treatment of OSCC. This ALG hydrogel prolongs the intratumoral retention of PtTe₂, ensuring sustained local availability. PtTe₂ exhibits tumor microenvironment-responsive catalytic activity, catalyzing the conversion of hydrogen peroxide into highly toxic hydroxyl radicals via Fenton-like reactions. Moreover, PtTe₂ possesses exceptional photothermal conversion efficiency, enabling precise, light-driven hyperthermia that selectively and effectively ablates tumor cells. By synergistically accelerating the kinetics of Fenton-like reactions through photothermal effects, the generation of reactive oxygen species is substantially amplified, effectively overwhelming the antioxidant defense system and achieving significant antitumor effects. Both in vitro and in vivo experiments demonstrated that the PtTe₂-ALG hydrogel achieved robust antitumor efficacy and excellent biosafety. Transcriptomic analyses revealed significant activation of apoptosis-related signaling cascades, elucidating the molecular mechanism of PtTe₂-based tumor therapy. By combining chemodynamic and photothermal therapy within a single, injectable platform, this work provides a promising, low-toxicity strategy for the clinical management of OSCC.

头颈部鳞状细胞癌是全球第六大常见恶性肿瘤，以口腔鳞状细胞癌（oral squamous cell carcinoma， OSCC）居多。目前治疗OSCC的临床标准为手术切除加放疗和化疗。然而，这种多模式方法与大量的发病率、显著的围手术期风险和频繁的系统性毒性相关，这些毒性明显损害了生活质量。因此，迫切需要新颖、更有效、更安全的治疗策略。本研究合成了PtTe2纳米棒，并将其包封在海藻酸钠（ALG）中，形成一种新型的可注射水凝胶，用于OSCC的精确治疗。这种ALG水凝胶延长了肿瘤内PtTe2的保留，确保了持续的局部可用性。PtTe2表现出肿瘤微环境响应的催化活性，通过芬顿样反应催化过氧化氢转化为高毒性羟基自由基。此外，PtTe2具有特殊的光热转换效率，可以实现精确的、光驱动的热疗，选择性地有效消融肿瘤细胞。通过光热效应协同加速fenton样反应动力学，大幅度放大活性氧的生成，有效压倒抗氧化防御系统，达到显著的抗肿瘤作用。体外和体内实验均表明，PtTe2-ALG水凝胶具有较强的抗肿瘤功效和良好的生物安全性。转录组学分析显示凋亡相关信号级联的显著激活，阐明了基于ptte2的肿瘤治疗的分子机制。通过将化学动力学和光热疗法结合在一个单一的、可注射的平台上，这项工作为OSCC的临床管理提供了一个有前途的、低毒性的策略。

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引用次数: 0

NFC-enabled sensing platform for the onsite determination of asparagine in food nfc传感平台，用于现场测定食品中的天冬酰胺

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2025-12-12 DOI: 10.1016/j.mtbio.2025.102675

Hong Seok Lee , Ravleen Kaur Panesar , Laura Gonzalez-Macia , Giandrin Barandun , Firat Güder

The formation of acrylamide, a potent neurotoxin, during the cooking of common foods like potatoes, and coffee presents a significant food safety challenge. This reaction is driven by free asparagine, yet current methods for its quantification are lab-based, slow, and expensive. To address this, we developed the first fully-integrated, batteryless, and wireless point-of-need sensor for rapid detection of free asparagine. Our innovation lies in coupling a disposable, chemically-functionalized paper-based gas sensor with a Near Field Communication (NFC) integrated circuit. This architecture allows a standard smartphone to wirelessly power the sensor and receive real-time data. The device operates by detecting ammonia gas, which is released during the enzymatic degradation of asparagine. Our proof-of-concept system achieves a detection limit of 3.28 μg/mL, sufficient for quantifying asparagine in food products. By eliminating the need for external power sources or readers, this technology provides a practical and cost-effective tool to improve quality control and safety in food manufacturing.

在烹饪土豆和咖啡等常见食物的过程中，丙烯酰胺（一种强效神经毒素）的形成对食品安全构成了重大挑战。这种反应是由游离的天冬酰胺驱动的，但目前的定量方法是基于实验室的，缓慢且昂贵。为了解决这个问题，我们开发了第一个完全集成的，无电池的，无线点需传感器，用于快速检测游离天冬酰胺。我们的创新在于将一次性、化学功能化的纸质气体传感器与近场通信（NFC）集成电路相结合。这种架构允许标准智能手机无线供电传感器并接收实时数据。该装置通过检测氨气来工作，氨气是在天冬酰胺酶降解过程中释放的。我们的概念验证系统的检测限为3.28 μg/mL，足以定量食品中的天冬酰胺。通过消除对外部电源或读取器的需求，该技术提供了一种实用且具有成本效益的工具，以改善食品制造中的质量控制和安全。

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引用次数: 0

Biomimetic nanovesicle with tri-pronged immune amplification for efficient photo-immunotherapy against triple-negative breast cancer 具有三叉免疫扩增的仿生纳米囊泡用于有效的光免疫治疗三阴性乳腺癌

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2025-12-11 DOI: 10.1016/j.mtbio.2025.102641

Wenwen Wang , Junyi Shao , Yilin Wan , Sen Zhou , Yingfen Jin , Youxia Xi , Xiaolin Ji , Jingjing Liu , Jingle Wang , Chunying Li , Zhiming Li

The limited response to immune checkpoint blockade (ICB) in triple-negative breast cancer (TNBC) is driven by both low intrinsic immunogenicity and a profoundly immunosuppressive tumor microenvironment (TME). Stimulator of interferon genes (STING) activation is a significant strategy to remodel the immunosuppressive TME by improving dendritic cells (DCs) maturation and M1-like macrophage polarization. However, the clinical translation of STING agonists is hampered by insufficient delivery efficiency. Herein, we integrate the 2′,3′-cGAMP, a kind of cyclic dinucleotide (CDN), with indocyanine green (ICG) into PD-1 overexpressed cell membrane vesicles (named as CDN@PM-ICG) for photo-immunotherapy. After systemic administration, CDN@PM-ICG nanovesicles accumulated at tumor region through high-affinity binding to PD-L1 overexpressed on neoplastic cells, effectively inhibiting the PD-1/PD-L1 axis and potentiating localized STING agonist delivery. Upon laser irradiation, ICG-mediated phototherapy induces immunogenic cell death (ICD), thereby elevating tumor immunogenicity and liberating damage associated molecular patterns (DAMPs). Subsequently, the released DAMPs, in combination with the STING activation, synergistically induces the maturation of DCs and promote the repolarization of tumor-associated macrophages (TAMs) toward the M1-like phenotype. This tri-pronged ICB/ICD/STING modulation paradigm augments cytotoxic T lymphocytes (CTLs) infiltration and ultimately inhibits tumor progression in a TNBC mouse model.

三阴性乳腺癌（TNBC）对免疫检查点阻断（ICB）的有限反应是由低内在免疫原性和深度免疫抑制肿瘤微环境（TME）驱动的。干扰素基因刺激因子（STING）激活是通过改善树突状细胞（DCs）成熟和m1样巨噬细胞极化来重塑免疫抑制TME的重要策略。然而，STING激动剂的临床翻译受到递送效率不足的阻碍。本研究将2 ',3 ' -cGAMP（一种环二核苷酸（CDN））与吲哚菁绿（ICG）整合到PD-1过表达的细胞膜囊泡（命名为CDN@PM-ICG）中进行光免疫治疗。系统给药后，CDN@PM-ICG纳米囊泡通过与肿瘤细胞上过表达的PD-L1的高亲和力结合在肿瘤区域积累，有效抑制PD-1/PD-L1轴并增强局部STING激动剂的递送。在激光照射下，icg介导的光疗诱导免疫原性细胞死亡（ICD），从而提高肿瘤免疫原性并释放损伤相关分子模式（DAMPs）。随后，释放的DAMPs与STING激活结合，协同诱导dc成熟，促进肿瘤相关巨噬细胞（tam）向m1样表型的再极化。在TNBC小鼠模型中，这种三管齐下的ICB/ICD/STING调节模式增加了细胞毒性T淋巴细胞（ctl）浸润并最终抑制肿瘤进展。

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引用次数: 0

Novel oat β-glucan nanoparticles for diabetes-associated colitis therapy 新型燕麦β-葡聚糖纳米颗粒治疗糖尿病相关结肠炎

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2025-12-11 DOI: 10.1016/j.mtbio.2025.102673

Yunhe Zheng , Yu Huang , Xi Chen , Jiangchuan He , Ting Wang , Hanchao Zhou , Kailai Liu , Yuchen Zhang , Jinpeng Wen , Jingya Qu , Qinyue Yu , Pengchong Wang , Ke Wang

The comorbidity of Inflammatory Bowel Disease and Diabetes Mellitus presents a formidable clinical challenge, as these conditions engage in vicious cycles mediated by intestinal barrier dysfunction, microbiota dysbiosis, and chronic inflammatory stress. This complex pathophysiological interplay substantially limits the efficacy of conventional monotherapeutic approaches. Therefore, we developed an innovative nanotherapeutic platform (BG@EGCG-Mn) that harnesses the synergistic potential of natural bioactive compounds. This platform combines the complementary biological activities of oat β-glucan (BG) and epigallocatechin gallate-Mn complex (EGCG-Mn). BG exerts multimodal therapeutic effects by modulating glucose absorption kinetics, thereby improving glycemic control and promoting intestinal barrier restoration through prebiotic mechanisms. Mn (Ⅱ) coordination stabilizes EGCG, preserving its dual therapeutic capacity: inhibition of α-glucosidase activity for hypoglycemia and potent free radical scavenging for anti-inflammatory action. The therapeutic mechanisms are distinctly complementary: BG primarily targets macroscopic barrier reconstruction and microbiota homeostasis, while EGCG-Mn operates at the cellular level to mitigate inflammation and metabolic dysregulation. Remarkably, BG@EGCG-Mn demonstrated robust therapeutic efficacy across multiple mice models, including acute UC, chronic UC, and diabetes-associated UC. This platform integrates four critical therapeutic modalities: hypoglycemic action, anti-inflammatory activity, barrier repair and gut microbiota modulation.This novel platform avoids antagonism in conventional drug combinations, significantly advancing treatment for metabolic-inflammatory diseases.

炎症性肠病和糖尿病的合并症是一个巨大的临床挑战，因为这些疾病参与由肠道屏障功能障碍、微生物群失调和慢性炎症应激介导的恶性循环。这种复杂的病理生理相互作用极大地限制了传统单一治疗方法的疗效。因此，我们开发了一种创新的纳米治疗平台（BG@EGCG-Mn），利用天然生物活性化合物的协同潜力。该平台结合了燕麦β-葡聚糖（BG）和表没食子儿茶素没食子酸锰复合物（EGCG-Mn）的互补生物活性。BG通过调节葡萄糖吸收动力学发挥多模式的治疗作用，从而通过益生元机制改善血糖控制，促进肠道屏障恢复。Mn（Ⅱ）配位稳定EGCG，保持其双重治疗能力：抑制α-葡萄糖苷酶活性，降低血糖，清除自由基，抗炎作用。治疗机制明显互补：BG主要针对宏观屏障重建和微生物群稳态，而EGCG-Mn在细胞水平上起作用，减轻炎症和代谢失调。值得注意的是，BG@EGCG-Mn在多种小鼠模型中显示出强大的治疗效果，包括急性UC，慢性UC和糖尿病相关的UC。该平台整合了四种关键的治疗模式：降糖作用、抗炎活性、屏障修复和肠道微生物群调节。这种新型平台避免了传统药物组合的拮抗作用，显著推进了代谢性炎症疾病的治疗。

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引用次数: 0

Melt-electrowriting fibrous scaffolds modified with nano-topography structures promoting cardiomyocytes synergistic contraction 纳米形貌结构修饰的熔融电解纤维支架促进心肌细胞协同收缩

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2025-12-11 DOI: 10.1016/j.mtbio.2025.102654

Jinqiao Jia , Qi Lei , Xiumei Zhang , Xiaomin Guan , Zhengjiang Liu , Jiapu Wang , Shilei Zhu , Ya Nan Ye , Di Huang

Melt-electrowriting (MEW) is an emerging strategy to fabricate microfibrous scaffolds that mimic the functional collagen fibers present in the native extracellular matrix (ECM). However, the main challenge remains in producing the nanoscale features that are widely found in ECM. In this work, MEW polycaprolactone (PCL) fibrous scaffolds with nano-topography structures (NS) were prepared to promote cell growth. Parallel PCL fibers were coated with NS by self-induced crystallization, which enhanced the adhesion and spreading of H9C2 cells. Compared with pristine scaffolds, the NS scaffolds exhibited improved hydrophilicity with a lower water contact angle of ∼50.70°. NS scaffolds exhibited abundant nano sites, which are beneficial for the cell-scaffold interaction and for achieving living constructs at a high cell density. Furthermore, NS scaffolds promoted cell-cell interactions and synergistic contraction of neonatal mouse cardiomyocytes (CMs). Dendritic pseudopods enabled CMs to spread along preferentially parallel to the direction of the lamellar. RNA sequencing analyses further revealed that the NS scaffolds upregulate cell cycle regulation-related pathways, cell communication-related pathways, calcium regulation-related pathways, cell motility-related pathways, and cellular adhesion and spreading-related pathways. It is envisioned that the proposed NS scaffolds may serve as promising candidates for tissue regeneration and biomedical engineering applications.

熔融电解（MEW）是一种新兴的制造微纤维支架的策略，它模仿天然细胞外基质（ECM）中存在的功能性胶原纤维。然而，主要的挑战仍然是如何产生广泛存在于ECM中的纳米级特征。本文制备了具有纳米形貌结构（NS）的聚己内酯（PCL）纤维支架，用于促进细胞生长。通过自诱导结晶的方法在平行PCL纤维表面包裹NS，增强了H9C2细胞的粘附和扩散。与原始支架相比，NS支架具有更低的水接触角（约50.70°），具有更好的亲水性。NS支架具有丰富的纳米位点，这有利于细胞-支架相互作用和实现高细胞密度的活结构。此外，NS支架促进了新生小鼠心肌细胞（CMs）的细胞间相互作用和协同收缩。树突伪足使CMs优先沿平行于片层方向扩散。RNA测序分析进一步揭示了NS支架上调细胞周期调控相关通路、细胞通讯相关通路、钙调节相关通路、细胞运动相关通路以及细胞粘附和扩散相关通路。设想所提出的NS支架可能成为组织再生和生物医学工程应用的有希望的候选者。

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引用次数: 0

Mechano-matching hydrogel patch promotes myocardial infarction repair via YAP-Bcl-2 pathway activation 机械匹配水凝胶贴片通过激活YAP-Bcl-2途径促进心肌梗死修复

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2025-12-11 DOI: 10.1016/j.mtbio.2025.102670

Yanyan Zhao , Jie Shen , Rurong Lin , Jianxing Huang , Xiaoming Zou , Honghao Hou , Xiaozhong Qiu

Although elastic cardiac patches have demonstrated efficacy in alleviating ventricular wall stress and restoring cardiac function following myocardial infarction (MI), the mechanistic basis governing their therapeutic effects remains incompletely elucidated. In this study, three distinct acellular hydrogel patches with tailored elastic moduli were fabricated, namely soft (1.61 kPa), mechano-matching (16.82 kPa, corresponding to the moduli of native adult myocardium), and rigid (602.61 kPa). These patches were implanted in a rat model of MI to evaluate their therapeutic potential. Among the three groups, the mechano-matching hydrogel patch exhibited superior performance, significantly improving cardiac function (with left ventricular ejection fraction [LVEF] elevated by 15.89 %, p = 0.002), reducing infarct size by 14.49 % (p < 0.001), mitigating myocardial fibrosis, and attenuating cardiomyocyte apoptosis. To dissect the underlying mechanism, an in vitro cyclic stretch model mimicking the in vivo myocardial mechanical microenvironment was established. Results revealed that hydrogels with moderate stiffness (16.82 kPa) transduced mechanical cues to promote nuclear translocation of Yes-associated protein (YAP) in cardiomyocytes. This key mechanotransduction event upregulated the expression of anti-apoptotic protein Bcl-2, thereby suppressing cardiomyocyte apoptosis. Notably, this study uncovers a previously unelucidated mechanistic paradigm by which moderate mechanical stimuli, matching the intrinsic stiffness of native myocardium, confer cardioprotection specifically through activation of the YAP-Bcl-2 signaling axis. Furthermore, it establishes that acellular biomaterials can exclusively harness their intrinsic mechanical properties to reverse pathological myocardial remodeling post-MI, without relying on cellular components or bioactive molecules. This finding provides strategy guided by mechanobiology for cardiac regeneration, substantially enhancing the clinical translatability of acellular cardiac patches.

尽管弹性心脏贴片在缓解心肌梗死（MI）后心室壁压力和恢复心功能方面具有疗效，但其治疗效果的机制基础仍未完全阐明。在本研究中，我们制作了三种不同的脱细胞水凝胶贴片，分别是柔软的（1.61 kPa）、机械匹配的（16.82 kPa，对应于天然成人心肌的模量）和刚性的（602.61 kPa）。将这些贴片植入心肌梗死大鼠模型以评估其治疗潜力。在三组中，机械匹配水凝胶贴片表现出优越的性能，显著改善心功能（左心室射血分数[LVEF]升高15.89%,p = 0.002），减少梗死面积14.49% (p < 0.001)，减轻心肌纤维化，减轻心肌细胞凋亡。为了探讨其机制，我们建立了模拟体内心肌力学微环境的体外循环拉伸模型。结果显示，中等硬度（16.82 kPa）的水凝胶可传导机械信号，促进心肌细胞中yes相关蛋白（YAP）的核易位。这一关键的机械转导事件上调抗凋亡蛋白Bcl-2的表达，从而抑制心肌细胞凋亡。值得注意的是，这项研究揭示了一个以前未阐明的机制范式，通过适度的机械刺激，匹配天然心肌的固有刚度，通过激活YAP-Bcl-2信号轴，特异性地赋予心脏保护。此外，它建立了非细胞生物材料可以完全利用其内在的力学特性来逆转心肌梗死后的病理性心肌重构，而不依赖于细胞成分或生物活性分子。这一发现为心脏再生提供了由机械生物学指导的策略，大大提高了无细胞心脏贴片的临床可翻译性。

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引用次数: 0

Engineered M2 macrophage-derived extracellular vesicles reprogram mitochondrial metabolism to alleviate temporomandibular joint cartilage degeneration 工程化的M2巨噬细胞来源的细胞外囊泡重新编程线粒体代谢以减轻颞下颌关节软骨变性

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2025-12-11 DOI: 10.1016/j.mtbio.2025.102674

Weiwen Ge , Lei Qi , Yun Wang , Jing Wang , Xin Fang , Shixue Lei , Dan Lin , Lei Zhang , Shanyong Zhang

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative joint disease characterized by progressive degradation of the cartilage matrix. Current clinical interventions mainly offer symptomatic relief but fail to halt disease progression. The pathogenesis of TMJOA is driven by mitochondrial dysfunction, which promotes both chondrocyte inflammation and extracellular matrix breakdown. To address these issues, an integrated therapeutic system was developed by encapsulating curcumin into M2 macrophage-derived extracellular vesicles (Cur@M2-EVs) through ultrasonic processing. In vitro studies demonstrated that Cur@M2-EVs effectively attenuated inflammatory responses and cartilage matrix degradation by scavenging reactive oxygen species (ROS), restoring mitochondrial membrane potential, and shifting cellular metabolism from glycolysis back to oxidative phosphorylation. Furthermore, transcriptomic analysis and experimental validation revealed that Cur@M2-EVs alleviate chondrocyte inflammation primarily by suppressing Thbs1 expression. To enable sustained drug release and enhance joint lubrication, Cur@M2-EVs were further encapsulated within poly (ethylene glycol) diacrylate (PEGDA) hydrogel microspheres, forming the Cur@M2-EVs@PEGDA system. In a monosodium iodoacetate (MIA)-induced rat model of TMJOA, intra-articular injection of Cur@M2-EVs@PEGDA microspheres significantly alleviated cartilage destruction and improved joint lubrication. This study proposes a novel disease-modifying strategy for TMJOA treatment by integrating mitochondrial regulation, immunomodulation, and sustained lubricating release within a single platform, offering a promising therapeutic approach for this challenging condition.

颞下颌关节骨性关节炎（TMJOA）是一种以软骨基质进行性退化为特征的退行性关节疾病。目前的临床干预措施主要提供症状缓解，但未能阻止疾病进展。TMJOA的发病机制是由线粒体功能障碍驱动的，线粒体功能障碍促进软骨细胞炎症和细胞外基质破坏。为了解决这些问题，我们开发了一种综合治疗系统，通过超声处理将姜黄素包封到M2巨噬细胞来源的细胞外囊泡（Cur@M2-EVs）中。体外研究表明，Cur@M2-EVs通过清除活性氧（ROS）、恢复线粒体膜电位、将细胞代谢从糖酵解转回氧化磷酸化，有效减轻炎症反应和软骨基质降解。此外，转录组学分析和实验验证表明Cur@M2-EVs主要通过抑制Thbs1的表达来减轻软骨细胞炎症。为了使药物持续释放并增强关节润滑，将Cur@M2-EVs进一步封装在聚乙二醇二丙烯酸酯（PEGDA）水凝胶微球中，形成Cur@M2-EVs@PEGDA体系。在碘乙酸钠（MIA）诱导的TMJOA大鼠模型中，关节内注射Cur@M2-EVs@PEGDA微球可显著减轻软骨破坏，改善关节润滑。本研究提出了一种新的TMJOA治疗策略，通过在单一平台内整合线粒体调节、免疫调节和持续润滑释放，为这一具有挑战性的疾病提供了一种有希望的治疗方法。

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引用次数: 0

Immunomodulatory role of decellularized extracellular matrix in skin wound healing 脱细胞细胞外基质在皮肤创面愈合中的免疫调节作用

IF 10.2 1区医学 Q1 ENGINEERING, BIOMEDICAL

Materials Today Bio

Pub Date : 2025-12-11 DOI: 10.1016/j.mtbio.2025.102672

Cininta Savitri , Hyun Su Park , Yeonjeong Kim , Young-Ju Jang , Jiyu Hyun , Dong-Hyun Lee , Mikyung Kang , Kyung Min Park , Suk Ho Bhang , Kwideok Park

The extracellular matrix (ECM) plays a pivotal role in skin wound healing by providing structural support and biochemical signals that regulate cellular behavior. Recent studies highlight the immunomodulatory properties of decellularized ECM (dECM), particularly its influence on macrophage polarization and the overall immune response, which are critical for effective tissue repair. During wound healing, macrophages transition from a pro-inflammatory to an anti-inflammatory phenotype, a process crucial for regulating angiogenesis, fibroblast proliferation, and tissue remodeling. Numerous studies have demonstrated that incorporating dECM into skin wound healing significantly enhances therapeutic outcomes by accelerating this phenotypic shift and fostering the transition to an anti-inflammatory environment. Furthermore, the decellularization process, which removes cellular components while preserving the ECM's biochemical and physical properties, has enabled the development of advanced scaffolds, hydrogels, and bioinks for biomedical applications. Despite these promising findings, the precise mechanisms underlying ECM-driven immune modulation remain unclear, limiting its full therapeutic potential of dECM in wound healing. This review summarizes current progress in ECM processing, applications, and immunological mechanisms in wound healing, with a particular focus on ECM-macrophage interactions. Additionally, it discusses future strategies for optimizing ECM-based, immunomodulation-driven approaches to wound healing.

细胞外基质（ECM）通过提供结构支持和调节细胞行为的生化信号，在皮肤伤口愈合中起着关键作用。最近的研究强调了脱细胞ECM （dECM）的免疫调节特性，特别是其对巨噬细胞极化和整体免疫反应的影响，这对有效的组织修复至关重要。在伤口愈合过程中，巨噬细胞从促炎表型转变为抗炎表型，这一过程对调节血管生成、成纤维细胞增殖和组织重塑至关重要。大量研究表明，将dECM纳入皮肤伤口愈合中，通过加速这种表型转变和促进向抗炎环境的过渡，显著提高了治疗效果。此外，脱细胞过程可以去除细胞成分，同时保留ECM的生化和物理特性，这使得生物医学应用的先进支架、水凝胶和生物墨水得以开发。尽管有这些有希望的发现，但ecm驱动的免疫调节的确切机制尚不清楚，限制了dECM在伤口愈合中的全部治疗潜力。本文综述了ECM加工、应用和伤口愈合中的免疫机制的最新进展，特别关注ECM与巨噬细胞的相互作用。此外，它还讨论了优化基于ecm的、免疫调节驱动的伤口愈合方法的未来策略。

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引用次数: 0