Biomaterials最新文献_第8页

Wireless magnetoelectric hydrogel spray reprograms the CXCL12-autophagy axis for spatiotemporally controlled cervical nerve root regeneration 无线磁电水凝胶喷雾重新编程cxcl12自噬轴，实现时空可控的颈神经根再生。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-03 DOI: 10.1016/j.biomaterials.2026.123983

Rongguo Yu , Jiamei Xiao , Zhencheng Xiong , Xiaoyang Wu , Chaoyi Zhang , Yusheng Zhang , Kangkang Huang , Jing Sun , Hongsong Fan , Hao Liu

Cervical nerve root injury (CNRI) presents significant clinical challenges owing to complex anatomical constraints and poor intrinsic regenerative capacity. In this study, we introduce an in situ-sprayable magnetoelectric hydrogel (DG/FBD) engineered through dynamic covalent assembly and photo-triggered stabilization. The construction of critical boronate ester bonding between dopamine-modified Fe₃O₄@BaTiO₃ nanoparticles and phenylboronic acid-functionalized dextran endows DG/FBD with optimal viscosity (87 mPa s), rapid gelation (<2s) and robust tissue adhesion (22.11 kPa), allowing for precise deposition along tortuous nerve roots while conforming to branched cervical anatomy. We then establish a wireless magnetic actuation platform with conductivity modulation enabled spatiotemporally controllable bioelectronic interfacing. In CNRI models loading with magnetic stimulation, we found the hydrogel spray significantly promotes axonal regeneration and myelination, and importantly, improving functional recovery, including enhanced pain and temperature sensation, as well as increased grip strength. We also demonstrate accelerated neural differentiation of BMSCs and attenuated astrogliosis by in vitro studies. Mechanistically, we reveal that magnetoelectrically triggered CXCL12 upregulation drives Schwann cells remodeling through PI3K/AKT/mTOR inhibition and enhances autophagic flux, establishing a bioelectronic-metabolic bridge where the CXCL12-autophagy axis emerges as a fundamental regulatory node for neural regeneration. Collectively, our work pioneers wireless magnetoelectric regulation of chemokine-directed neural repair via an integrated sprayable hydrogel system that overcomes cervical interfacing constraints, establishing a promising platform for spatiotemporal microenvironmental reprogramming in complex neuropathies.

颈神经根损伤（CNRI）由于其复杂的解剖限制和较差的内在再生能力，给临床带来了重大挑战。在这项研究中，我们介绍了一种通过动态共价组装和光触发稳定化设计的可现场喷涂的磁电水凝胶（DG/FBD）。在多巴胺修饰的Fe3O4@BaTiO3纳米颗粒和苯硼酸功能化的葡聚糖之间建立了临界硼酸酯键，使DG/FBD具有最佳粘度（87 mPa s）、快速凝胶化(

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引用次数: 0

Adaptive hydrogel platform for nitric oxide release and post-infarction cardiac microenvironment modulation 自适应水凝胶平台一氧化氮释放和梗死后心脏微环境调节。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-03 DOI: 10.1016/j.biomaterials.2026.123980

Yu Wu , Wen Zhang , Linlin Huang , Xinping Xu , Yue Wang , Long Bai , Li Yang , Cheng Hu , Yunbing Wang

After myocardial infarction (MI), oxidative stress, inflammatory response and myocardial fibrosis severely impair tissue regeneration. Aiming at the problem that multifunctional hydrogel systems are difficult to achieve precise therapeutic regulation due to limited response characteristics and insufficient synergistic effect. Here, we developed an adaptive hydrogel platform for targeted nitric oxide (NO) release and post-infarction cardiac microenvironment modulation. A small molecule phenylboronic acid-based cross-linker (N(BA)₄) with a four-arm topology was reported for the first time, and it was combined with Nitroso glutathione (GSNO)-modified polyvinyl alcohol (PVA) to prepare the hydrogel platform. For the multi-stage of myocardial repair, bioactive microspheres with programmed delivery function were prepared, which could rapidly release the salvianolic acid B in the pre-infarct stage to exert antioxidant and pro-angiogenic effects, and continuously release the fibrosis inhibitor Galunsertib in the post-infarct stage to inhibit fibrosis. The pathologically responsive composite hydrogel system enables precise and efficient MI therapy through a cascade-triggered drug release mechanism and multi-pathway synergy. It provides a novel and promising strategy to overcome the challenges of different pathological stages in the infarcted cardiac microenvironment.

心肌梗死（MI）后，氧化应激、炎症反应和心肌纤维化严重损害组织再生。针对多功能水凝胶系统反应特性有限、协同效应不足难以实现精准治疗调控的问题。在这里，我们开发了一种靶向一氧化氮（NO）释放和梗死后心脏微环境调节的自适应水凝胶平台。首次报道了一种具有四臂拓扑结构的小分子苯硼酸交联剂N(BA)4，并将其与亚硝基谷胱甘肽（GSNO）改性聚乙烯醇（PVA）结合制备水凝胶平台。针对多阶段心肌修复，制备具有程序化递送功能的生物活性微球，可在梗死前快速释放丹酚酸B，发挥抗氧化和促血管生成作用，在梗死后持续释放纤维化抑制剂Galunsertib，抑制纤维化。病理反应性复合水凝胶系统通过级联触发的药物释放机制和多途径协同作用，能够精确有效地治疗心肌梗死。它为克服梗死心脏微环境中不同病理阶段的挑战提供了一种新颖而有前途的策略。

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引用次数: 0

Extracellular vesicles secreted by LRP1+ ligament-derived stem cells promote tendon-bone healing after ACL reconstruction via miR-708-5p/Bambi axis LRP1+韧带源性干细胞分泌的细胞外囊泡通过miR-708-5p/Bambi轴促进ACL重建后肌腱-骨愈合

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-03 DOI: 10.1016/j.biomaterials.2026.123977

Pengling Yao , Yuying Yang , Feifei Yuan , Ziyang Lin , Yiming Qin , Shen Liu , Yiyang Mao , Linfeng Wang , Ruixue Du , Yiting Xu , Chengjun Li , Hongbin Lu , Tao Zhang

Anterior cruciate ligament (ACL) rupture often requires reconstruction surgery, with a key postoperative challenge being robust integration between the graft and bone tunnel. Studies have shown that extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) can enhance tendon-bone healing strength. As tissue-resident stem cells in the ACL, ligament-derived stem cells (LDSCs) are among the first activated after injury, migrating to the damaged site to participate in regenerative repair. In this study, single-cell RNA sequencing (scRNA-seq) of human ACL remnant samples revealed that LRP1-positive LDSCs (LRP1⁺LDSCs) have significantly stronger stemness and chondrogenic differentiation potential than LRP1-negative ones. Based on this, EVs from LRP1⁺LDSCs (LRP1⁺LDSCs-EVs) were isolated and delivered into bone tunnels of a rat ACL reconstruction (ACLR) model using gelatin methacryloyl (GelMA) hydrogel as a carrier. Results showed that LRP1⁺LDSCs-EVs effectively promoted cartilage regeneration at the tendon-bone interface (TBI) post-ACLR and significantly improved biomechanical function recovery. MiRNA sequencing characterized the miRNA cargo in LRP1⁺LDSCs-EVs, identifying highly enriched miR-708-5p as a key mediator. This miRNA directly binds to and suppresses Bambi mRNA expression, reducing Bambi protein's competitive inhibition of BMP signaling (Bambi acts as a decoy receptor for the TGF-β pathway). This mechanism activates chondrogenic differentiation and promotes TBI regenerative healing. Overall, EVs from the LRP1-positive LDSCs subpopulation significantly enhance graft-bone tunnel integration efficiency after ACLR, providing a novel targeted and efficient cell-free therapeutic strategy for enhancing tendon-bone integration in orthopedic surgery.

前交叉韧带（ACL）断裂通常需要重建手术，术后的关键挑战是移植物与骨隧道之间的坚固整合。研究表明，间充质干细胞（MSCs）分泌的细胞外囊泡（EVs）可以增强肌腱骨愈合强度。韧带源性干细胞（韧带源性干细胞）作为前交叉韧带中的组织常驻干细胞，是损伤后最先激活的干细胞之一，可迁移到受损部位参与再生修复。本研究通过对人ACL残体样本进行单细胞RNA测序（scRNA-seq）发现，LRP1阳性LDSCs （LRP1+LDSCs）的干性和软骨分化潜能明显强于LRP1阴性LDSCs。在此基础上，分离LRP1+LDSCs （LRP1+LDSCs- ev）的EVs，并以明胶甲基丙烯酰（GelMA）水凝胶为载体，将其注入大鼠ACL重建（ACLR）模型的骨隧道中。结果表明，LRP1+ ldscs - ev可有效促进aclr后肌腱-骨界面（TBI）软骨再生，显著改善生物力学功能恢复。MiRNA测序表征了LRP1+ ldscs - ev中的MiRNA货物，鉴定出高富集的miR-708-5p是一个关键的中介。该miRNA直接结合并抑制Bambi mRNA表达，减少Bambi蛋白对BMP信号传导的竞争性抑制（Bambi作为TGF-β途径的诱饵受体）。这一机制激活软骨分化，促进创伤性脑损伤再生愈合。总体而言，来自lrp1阳性LDSCs亚群的ev显著提高ACLR后移植物-骨隧道整合效率，为增强骨科手术中肌腱-骨整合提供了一种新的靶向和有效的无细胞治疗策略。

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引用次数: 0

Engineering a Wnt-activated osteomimetic microenvironment with iPSC-derived MSCs for synergistic bone regeneration, angiogenesis, and neurogenesis 利用ipsc衍生的MSCs构建wnt激活的仿骨微环境，用于协同骨再生、血管生成和神经发生。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-03 DOI: 10.1016/j.biomaterials.2026.123978

Qiqi Bu , Hao Bai , Minjie Ruan , Lu Gao , Liuqing Wang , Mao Nie , Mingming Zhao , Xiaolin Tu , Chengzhu Zhao

To advance the bioactivity of artificial bone grafts, human induced pluripotent stem cell (hiPSC)-derived mesenchymal stem cells (iMSCs) are ideal seed cells. However, the instability in iMSC generation and their limited osteogenic capacity challenge their clinical application. In this study, we applied a novel strategy that combines a stable iMSC induction method that mimics the developmental process with an osteocytic Wnt-based osteogenic microenvironment, with the aim of creating a scalable, mechanistically defined platform to enhance bone regenerative efficiency. The small-molecule Wnt activator SKL2001-treated osteocyte osteogenic microenvironment (SOOME) substantially enhanced the osteogenic differentiation of iMSCs and promoted iMSCs-mediated bone defect repair in a rat femoral condyle defect model. Moreover, the SOOME-iMSC composite demonstrated its ability to promote angiogenesis and neurogenesis both in vitro and in vivo, and also enhanced osteoclast activity at the regeneration site. These findings suggest that the SOOME-treated iMSCs create a native-like osteomimetic microenvironment, which improves implant integration and bone tissue regeneration. This approach introduces a novel strategy for the standardized fabrication of seed cells with enhanced osteogenic potential, offering a promising solution for the fabrication and clinical application of bioactive bone graft materials.

为了提高人工骨移植物的生物活性，人诱导多能干细胞（hiPSC）衍生的间充质干细胞（iMSCs）是理想的种子细胞。然而，iMSC生成的不稳定性及其有限的成骨能力给其临床应用带来了挑战。在这项研究中，我们采用了一种新的策略，将模拟发育过程的稳定iMSC诱导方法与基于骨细胞wnt的成骨微环境相结合，目的是创建一个可扩展的、机械定义的平台来提高骨再生效率。在大鼠股骨髁缺损模型中，小分子Wnt激活剂skl2001处理的骨细胞成骨微环境（SOOME）显著增强了iMSCs的成骨分化，促进了iMSCs介导的骨缺损修复。此外，SOOME-iMSC复合材料在体外和体内均显示出促进血管生成和神经生成的能力，并增强了再生部位的破骨细胞活性。这些研究结果表明，soome处理的iMSCs创造了一个类似天然的仿骨微环境，从而改善了种植体的整合和骨组织再生。该方法为具有增强成骨潜能的种子细胞的标准化制备提供了一种新的策略，为生物活性骨移植材料的制备和临床应用提供了一种有前景的解决方案。

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引用次数: 0

Mitochondria-targeted co-assembled nanosystem with multimodal mitochondrial DNA level control to alleviate inflammation and promote chronic wound healing 线粒体靶向共组装纳米系统与多模态线粒体DNA水平控制减轻炎症和促进慢性伤口愈合

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-03 DOI: 10.1016/j.biomaterials.2026.123981

Xueyan Mao , Chuanwen Wang , Shufan Yu , Kai Zhang , Zheng Wang , Jing Du , Ying Kong , Alberto Bianco , Shaohua Ge , Baojin Ma

Mitochondrial dysfunction, particularly when associated with the mitochondrial DNA (mtDNA) activated cGAS-STING signaling pathway, represents a key pathogenic mechanism contributing to excessive inflammation. Therapeutic targeting of mitochondrial homeostasis coupled with precise modulation of mtDNA release emerges as a promising yet underexplored strategy to suppress pathological inflammation and promote chronic wound healing. Herein, epigallocatechin gallate-quercetin co-assembled nanoparticles (EQ NPs) were engineered to inhibit mtDNA-mediated inflammatory cascades through mitochondria-targeted multimodal mtDNA level control. Primarily, EQ NPs reduced the formation of oxidized mtDNA fragments (Ox-mtDNA). Then, EQ NPs inhibited the excessive opening of the mitochondrial permeability transition pore, preventing Ox-mtDNA cytoplasmic leakage. Subsequently, the escaped mtDNA fragments were neutralized by EQ NPs through polyphenol-mediated adsorption. Finally, mitophagy was upregulated to selectively eliminate damaged mitochondria. This well-designed strategy significantly inhibited the activation of the mtDNA-mediated cGAS-STING pathway, relieved the release of inflammatory factors, and promoted anti-inflammatory phenotype polarization of macrophages. In vivo, EQ NPs promoted chronic wound healing by bacteriostasis, anti-inflammation, immunomodulation, and accelerated angiogenesis. Overall, the study establishes a sequential mitochondrial quality control paradigm in which the inflammatory cascade is interrupted by multimodal and full-chain mtDNA scavenging, providing a promising candidate for the treatment of inflammatory diseases and chronic wound healing.

线粒体功能障碍，特别是与线粒体DNA （mtDNA）激活的cGAS-STING信号通路相关的线粒体功能障碍，是导致过度炎症的关键致病机制。靶向治疗线粒体稳态并精确调节mtDNA释放是抑制病理性炎症和促进慢性伤口愈合的一种有希望但尚未得到充分探索的策略。本研究设计了表没食子儿茶素没食子酸槲皮素共组装纳米颗粒（EQ NPs），通过线粒体靶向的多模态mtDNA水平控制抑制mtDNA介导的炎症级联反应。首先，EQ NPs减少了氧化mtDNA片段（Ox-mtDNA）的形成。然后，EQ NPs抑制线粒体通透性过渡孔过度开放，防止Ox-mtDNA细胞质渗漏。随后，逃逸的mtDNA片段通过多酚介导的吸附被EQ NPs中和。最后，上调线粒体自噬以选择性地消除受损的线粒体。这一精心设计的策略显著抑制了mtdna介导的cGAS-STING通路的激活，缓解了炎症因子的释放，促进了巨噬细胞的抗炎表型极化。在体内，EQ NPs通过抑菌、抗炎、免疫调节和加速血管生成来促进慢性伤口愈合。总体而言，该研究建立了一个序列线粒体质量控制范式，其中炎症级联被多模式和全链mtDNA清除中断，为炎症性疾病和慢性伤口愈合的治疗提供了一个有希望的候选物。

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引用次数: 0

Enhanced MSC spheroid adhesion on 3D-printed leaf-stacked scaffolds for functional tracheal regeneration 3d打印叶片堆叠支架增强骨髓间充质干细胞球体黏附，用于功能性气管再生

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-03 DOI: 10.1016/j.biomaterials.2026.123982

Sang-Yoon Han , Jae Keun Park , Ji Suk Choi , Eun Ji Jeong , Min Rye Eom , Ji Min Seok , Min Ji Kim , Su A. Park , Se Heang Oh , Seong Keun Kwon

Reconstruction of segmental tracheal defects using three-dimensional (3D)-printed scaffolds remains a formidable challenge. While polycaprolactone (PCL) is widely utilized for its mechanical integrity, its inherent hydrophobicity limits cellular adhesion and tissue integration. In this study, we developed a 3D-printed PCL tracheal scaffold featuring a Leaf-Stacked Structure (LSS) and evaluated a spatially organized Mesenchymal Stem Cell (MSC) delivery strategy for functional regeneration. MSC spheroids were employed to overcome the limitations of monolayer cells, as their 3D configuration creates an internal hypoxic core that upregulates angiogenic and anti-inflammatory genes, thereby maximizing paracrine-mediated tissue repair. In vitro analyses, including cell adhesion assays and indirect co-culture systems, demonstrated that the LSS topography significantly enhanced the adhesion of both monolayer MSC and spheroids compared to plain PCL. Furthermore, MSC spheroids markedly promoted the proliferation and migration of human small airway epithelial cells. Based on these findings, we compared five experimental groups in a rabbit tracheal defect model: (1) Native, (2) No MSC, (3) Inner MSC (monolayer), (4) Outer spheroid, and (5) Dual group (combined inner monolayer and outer spheroids). In vivo, the Dual group exhibited the most robust mucosal regeneration, alongside an immunomodulatory shift toward increased M2/M1 macrophage ratios. Although neovascularization was prominent at MSC implantation sites, lineage analysis via β2-microglobulin tracking revealed that vessel-forming cells were primarily host-derived. This confirms that implanted MSC survived for 14 weeks and orchestrated regeneration predominantly through paracrine mechanisms.

Collectively, the integration of LSS topography and spatially organized MSC represents a promising synergistic strategy for functional tracheal reconstruction.

利用三维打印支架重建气管节段性缺损仍然是一个艰巨的挑战。虽然聚己内酯（PCL）因其机械完整性而被广泛应用，但其固有的疏水性限制了细胞的粘附和组织的整合。在这项研究中，我们开发了一种具有叶片堆叠结构（LSS）的3d打印PCL气管支架，并评估了用于功能再生的空间组织间充质干细胞（MSC）递送策略。MSC球体被用来克服单层细胞的局限性，因为它们的3D结构创造了一个内部缺氧核心，上调血管生成和抗炎基因，从而最大限度地提高旁分泌介导的组织修复。体外分析，包括细胞粘附试验和间接共培养系统，表明与普通PCL相比，LSS地形显著增强了单层MSC和球体的粘附。此外，间充质干细胞球体显著促进人小气道上皮细胞的增殖和迁移。在此基础上，我们比较了兔气管缺损模型的5个实验组：(1)天然、(2)无间充质干细胞、(3)内间充质干细胞（单层）、(4)外球体和(5)双重组（内单层和外球体结合）。在体内，Dual组表现出最强劲的粘膜再生，同时免疫调节向M2/M1巨噬细胞比例增加。尽管新生血管在间充质干细胞植入部位很突出，但通过β2微球蛋白追踪的谱系分析显示，血管形成细胞主要来自宿主。这证实了植入的MSC存活了14周，并主要通过旁分泌机制进行再生。总的来说，LSS地形和空间组织的MSC的整合代表了功能性气管重建的一个有前途的协同策略。

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引用次数: 0

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