Biomaterials最新文献_第6页

Biomimetic cascade “four-in-one” Nanozyme for remodeling the redox tumor microenvironment and disrupting energy homeostasis to enhance ferroptosis against triple-negative breast cancer 仿生级联“四合一”纳米酶重塑氧化还原肿瘤微环境和破坏能量稳态以增强铁凋亡对抗三阴性乳腺癌

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-12 DOI: 10.1016/j.biomaterials.2026.124001

Lei Li , Annan Liu , Ze Wang , Hao Liang , Andrew K. Whittake , Hui Guo , Quan Lin

Ferroptosis, a promising therapeutic strategy for triple-negative breast cancer (TNBC), faces significant challenges due to intrinsic tumor defense mechanisms. To enhance ferroptosis against TNBC, a biomimetic “four-in-one' cascade nanozyme AuPd/Cu₂O@Cancer cell membrane (APCM) was engineered to remodel tumoral redox microenvironment and disrupt cancer cell energy metabolism. APCM nanozyme integrates four enzyme-mimicking activities into a single nanoplatform, including peroxidase-like, glucose oxidase-like, catalase-like, and glutathione peroxidase-like. This synergistic cascade converts endogenous H₂O₂ to cytotoxic ·OH, depletes glucose to block energy supply while self-supplying H₂O₂, alleviates hypoxia, and depletes glutathione to suppress antioxidant defense, collectively triggering lethal reactive oxygen species (ROS) accumulation for ferroptosis. APCM further enables photothermal therapy (PTT), inducing direct thermal ablation and providing localized heat to augment nanocatalytic efficacy. Coating with tumor-derived membrane facilitates homologous targeting and immune evasion. Transcriptomic analysis confirmed profound APCM-mediated modulation of ferroptosis, metabolic, and redox-associated gene signatures. Notably, the APCM nanozyme enables dual-mode imaging, offering visualization of the location of TNBC and precise guidance for treatment. Collectively, this “four-in-one' biomimetic nanozyme, which integrates multiple enzyme-mimicking activities and tumor-cell-membrane camouflage, effectively disrupts redox and metabolic homeostasis to potentiate ferroptosis, establishing a promising therapeutic paradigm for TNBC.

上睑下垂作为一种很有前景的治疗三阴性乳腺癌的策略，由于其固有的肿瘤防御机制而面临重大挑战。为了增强对TNBC的铁凋亡，设计了一种仿生“四合一”级联纳米酶AuPd/Cu2O@Cancer细胞膜（APCM）来重塑肿瘤氧化还原微环境并破坏癌细胞的能量代谢。APCM纳米酶将四种酶模拟活性整合到一个纳米平台上，包括过氧化物酶样、葡萄糖氧化酶样、过氧化氢酶样和谷胱甘肽过氧化物酶样。这一协同级联作用将内源性H2O2转化为细胞毒性·OH，在自供H2O2的同时消耗葡萄糖阻断能量供应，缓解缺氧，消耗谷胱甘肽抑制抗氧化防御，共同引发致死性活性氧（ROS）积累，导致铁沉。APCM进一步实现光热疗法（PTT），诱导直接热消融并提供局部热量以增强纳米催化效果。肿瘤源性膜涂层有利于同源靶向和免疫逃避。转录组学分析证实了apcm介导的铁下垂、代谢和氧化还原相关基因特征的深刻调节。值得注意的是，APCM纳米酶可以实现双模式成像，提供TNBC位置的可视化和精确的治疗指导。总的来说，这种“四位一体”的仿生纳米酶，整合了多种酶模拟活性和肿瘤细胞膜伪装，有效地破坏氧化还原和代谢稳态，从而增强铁凋亡，为TNBC建立了一个有希望的治疗范例。

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引用次数: 0

Shaping mesenchymal stem cell fate with a two-dimensional covalent triazine framework for calmodulin modulation 钙调素调控的二维共价三嗪框架塑造间充质干细胞命运

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-11 DOI: 10.1016/j.biomaterials.2026.123997

Lei Wang , Boyu Zheng , Maryam Salahvarzi , Yi-An Yang , Yan Nie , Philip Nickl , Mathias Dimde , Kai Ludwig , Xun Xu , Yiduo Zhou , Junyao Zhang , Weiwei Wang , Xiao Ling , Xingjun Qin , Lukas Prantl , Oliver Felthaus , Wenzhong Li , Mohsen Adeli , Nan Ma

Calmodulin (CaM) is a central calcium sensor and signaling hub that critically governs stem cell fate. However, directly intracellular modulation of CaM remains challenging due to its activity is tightly coupled to finely balanced calcium homeostasis, and conventional chemicals or biomaterials have limited ability to access or target it. Here, we introduce a novel two-dimensional, porous, covalent triazine-based framework, CTF-Ca, synthesized under ambient conditions, that offers a new strategy for intracellular CaM regulation. Unlike conventional approaches, CTF-Ca bypasses membrane calcium channels, enabling direct calcium influx into mesenchymal stem cells (MSCs) and triggering robust, sustained activation of the Ca²⁺/CaM signaling pathway. This activation markedly enhances osteogenic differentiation in MSCs. Remarkably, CTF-Ca also compensates for suppressed CaM function, restoring osteogenic potential in MSCs even under CaM-inhibited conditions. This compensatory effect was further demonstrated in C2C12 myogenic progenitor cells, a skeletal muscle model characterized with high endogenous CaM expression, where CTF-Ca rescued myotube formation in CaM deficient cells, underscoring its broad applicability. Together, these findings establish CTF-Ca as an effective 2D material for direct intracellular modulation of CaM, offers a promising new tool for regulating stem and progenitor cells fate.

钙调蛋白（Calmodulin, CaM）是一种重要的钙传感器和信号中枢，对干细胞的命运起着至关重要的作用。然而，直接在细胞内调节CaM仍然具有挑战性，因为它的活性与精细平衡的钙稳态紧密相关，而传统的化学物质或生物材料对其的接近或靶向能力有限。在这里，我们介绍了一种在环境条件下合成的新型二维、多孔、共价三嗪基框架CTF-Ca，它为细胞内CaM调控提供了一种新的策略。与传统方法不同，CTF-Ca绕过膜钙通道，使钙直接流入间充质干细胞（MSCs），并触发Ca2+/CaM信号通路的持续激活。这种激活显著增强了间充质干细胞的成骨分化。值得注意的是，CTF-Ca也补偿了CaM抑制的功能，即使在CaM抑制的条件下也能恢复MSCs的成骨潜能。这种代偿作用在C2C12肌源性祖细胞中得到进一步证实，C2C12肌源性祖细胞是一种内源性CaM高表达的骨骼肌模型，在C2C12肌源性祖细胞中，CTF-Ca挽救了CaM缺陷细胞的肌管形成，强调了其广泛的适用性。总之，这些发现表明CTF-Ca是一种有效的二维材料，可以直接在细胞内调节CaM，为调节干细胞和祖细胞的命运提供了一种有前途的新工具。

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引用次数: 0

Self-reinforced photothermal-immunomodulation potentiating ISR-ICD cascade against postoperative relapse 自增强光热免疫调节增强ISR-ICD级联预防术后复发

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-10 DOI: 10.1016/j.biomaterials.2026.123995

Yiming Liu , Jiheng Shan , Chengzhi Zhang , Junheng Zhang , Yilin Liu , Changlong Li , Peiyao Sun , Dechao Jiao , Haidong Zhu , Zhen Li , Xinwei Han , Yanan Zhao

Postoperative liver cancer relapse remains a formidable clinical challenge. Photothermal therapy (PTT) holds promise by eliminating residual malignancies and activating antitumor immunity; notably, tumor cells persistently reconstitute proteostasis and survive by integrated stress response (ISR)-mediated heat shock protein 90 (HSP90) activation to constrain PTT efficacy. To address this limitation, we engineered a self-reinforced photothermal-immunomodulation strategy based on electrospun nanofiber scaffolds co-loaded with black phosphorus nanosheets (BPNSs) and the HSP90 inhibitor 17-DMAG. These nanofiber scaffolds exhibited robust hydrophobicity, efficient photothermal conversion, and near-infrared (NIR) responsive controlled drug release. Under NIR irradiation, the nanofiber scaffolds leveraged BPNSs to generate stable PTT while liberating 17-DMAG to amplify proteotoxicity, forcibly redirecting the ISR from pro-survival adaptation toward robust apoptosis and immunogenic cell death (ICD). Consequently, prominently exposed damage-associated molecular patterns potentiated tumor immunogenicity and remodeled immune microenvironment by dendritic cells maturation, cytotoxic T lymphocytes (CTLs) priming, and immunosuppressive populations reprogramming. Crucially, subsequent synergy with anti-PD-L1 reinvigorated CTLs and established durable immune memory. Systematic validation confirmed this localized strategy uniquely integrates precision photothermal energy conversion with potent ISR-ICD cascade, effectively synergizing with anti-PD-L1 to suppress postoperative liver cancer relapse and metastasis, thereby holding substantial translational potential for clinical oncology.

肝癌术后复发仍然是一个巨大的临床挑战。光热疗法（PTT）有望消除残留的恶性肿瘤和激活抗肿瘤免疫；值得注意的是，肿瘤细胞持续重建蛋白平衡，并通过综合应激反应（ISR）介导的热休克蛋白90 （HSP90）激活来抑制PTT的疗效。为了解决这一限制，我们设计了一种基于静电纺丝纳米纤维支架的自增强光热免疫调节策略，该支架共负载黑磷纳米片（BPNSs）和HSP90抑制剂17-DMAG。这些纳米纤维支架具有强大的疏水性，高效的光热转换和近红外（NIR）响应控制药物释放。在近红外照射下，纳米纤维支架利用BPNSs产生稳定的PTT，同时释放17-DMAG以增强蛋白质毒性，强行将ISR从促生存适应转向强大的凋亡和免疫原性细胞死亡（ICD）。因此，突出暴露的损伤相关分子模式增强了肿瘤免疫原性，并通过树突状细胞成熟、细胞毒性T淋巴细胞（ctl）启动和免疫抑制群体重编程重塑了免疫微环境。至关重要的是，随后与抗pd - l1的协同作用重新激活了ctl并建立了持久的免疫记忆。系统验证证实，该本地化策略独特地将精确光热转换与强大的ISR-ICD级联结合起来，有效地与抗pd - l1协同抑制肝癌术后复发和转移，从而在临床肿瘤学中具有巨大的转化潜力。

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引用次数: 0

Tuning hydrogel affinity to control the release of antibodies 调节水凝胶亲和力来控制抗体的释放

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-10 DOI: 10.1016/j.biomaterials.2026.123996

Daniela Isaacs-Bernal , Brenda Coles , Lia Huo , Noor E. Bahsoun , Siming Wang , Derek van der Kooy , Molly S. Shoichet

The discovery of specific affinity interactions has paved the way for the development of functional hydrogel systems that enable tunable protein release via non-covalent interactions. This study explores, for the first time, the controlled release of antibody-based therapeutics via affinity interactions with specific fragment crystallizable domain peptide ligands (FcLs) immobilized within a hydrogel system. As a proof of concept, a dual-antibody delivery strategy was designed to stimulate retinal stem cells in the adult mammalian eye, co-releasing Fc-Noggin (targeting bone morphogenic proteins) and anti-sFRP2 (targeting secreted frizzle related protein-2). An FcL capable of binding to both Fc-Noggin and anti-sFRP2 with comparable affinity (10⁻⁸ M) was functionalized onto a hyaluronan-based hydrogel that leverages oxime chemistry for network crosslinking and inverse electron demand Diels-Alder for FcL conjugation. In vitro, FcL1-functionalized hydrogels exhibited affinity-mediated retention of these therapeutics, reducing burst release and preserving protein stability. In vivo, a single intravitreal injection of the hydrogel formulation activated retinal stem cells, in adult CD1 mice, over four days to a similar extent as 3 repeated bolus injections of Fc-Noggin and anti-sFRP2 in saline, demonstrating the advantage of hydrogel-based delivery over bolus administration. This platform technology holds significant potential for broader application to other antibody-based therapies and offers a promising approach for local delivery in the eye.

特异性亲和相互作用的发现为开发功能性水凝胶系统铺平了道路，该系统可以通过非共价相互作用实现可调节的蛋白质释放。本研究首次探索了通过与固定在水凝胶系统中的特定片段结晶结构域肽配体（FcLs）的亲和相互作用来控制基于抗体的治疗药物的释放。作为概念的证明，设计了一种双抗体递送策略来刺激成年哺乳动物眼睛中的视网膜干细胞，共同释放Fc-Noggin（靶向骨形态发生蛋白）和抗sfrp2（靶向分泌的卷曲相关蛋白-2）。FcL能够与Fc-Noggin和抗sfrp2结合，具有相当的亲和力（10 - 8 M），被功能化到基于透明质酸的水凝胶上，该水凝胶利用肟化学进行网络交联，利用逆电子需求Diels-Alder进行FcL共轭。在体外，fcl1功能化的水凝胶表现出亲和介导的这些疗法的保留，减少爆发释放并保持蛋白质稳定性。在体内，在成年CD1小鼠中，单次玻璃体内注射水凝胶制剂激活视网膜干细胞超过4天，其程度与3次重复注射Fc-Noggin和生理盐水中的抗sfrp2相似，表明基于水凝胶的给药优于单次给药。该平台技术具有广泛应用于其他基于抗体的治疗的巨大潜力，并为眼部局部递送提供了一种有前景的方法。

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引用次数: 0

Synergistic intercellular junction and anti-inflammation wound healing therapy via bioengineered hybrid nanovesicles 通过生物工程杂交纳米囊泡协同细胞间连接和抗炎症伤口愈合治疗

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-10 DOI: 10.1016/j.biomaterials.2026.123999

Shi-Yi Zhang , Zhi-Ying He , Ze-Rui Zhou , Han-Bin Xu , Shi-Yu Zheng , Xin-Yue Liu , Meng-Qi Zhao , Bin-Bin Chen , Da-Wei Li , Ruo-Can Qian , Jiang-Wei Tian

Impaired skin wound healing with excessive inflammation affects millions of patients globally. The resulting chronic pain can severely impact the quality of life for people afflicted by the condition. However, the treatment of skin wounds faces enormous challenges due to complex wound microenvironments. Here, we report the design of bioengineered hybrid nanovesicles (BHNVs) that enable advanced wound healing by concurrently providing effective intercellular junction and inflammation relief. The surface of hybrid nanovesicles is modified by trans-membrane DNA functional structures with a zipper part at the outside and a DNAzyme signal output part at the inside. Asiaticoside, an active ingredient from herbal medicines, and signal recognition DNA complex are encapsulated into the nanovesicles. From both outside and inside, these components of the hybrid nanovesicles work synergistically to address wound healing from both extra- and intracellular perspectives. Upon vesicle-cell fusion, the zipper part at the outside can facilitate cell-cell junction, and the DNAzyme signal output part at the inside can hinder while monitoring inflammatory responses. The released Asiaticoside can improve cell proliferation, enhance angiogenesis, accelerate cell migration/adhesion, and promote wound healing with the combination effect of anti-oxidation and anti-ulceration. Together, BHNVs are shown to successfully accelerate wound healing and prevent inflammation. Favorable therapeutic outcomes are achieved both in vitro and in vivo, indicating a robust modality for local wound management with enhanced therapeutic effects.

皮肤伤口愈合受损并伴有过度炎症影响着全球数百万患者。由此产生的慢性疼痛会严重影响患者的生活质量。然而，由于复杂的伤口微环境，皮肤伤口的治疗面临着巨大的挑战。在这里，我们报道了生物工程杂交纳米囊泡（bhnv）的设计，它通过同时提供有效的细胞间连接和炎症缓解来实现高级伤口愈合。杂化纳米囊泡表面采用外拉链部分、内DNAzyme信号输出部分的跨膜DNA功能结构修饰。将中药活性成分积雪草苷和信号识别DNA复合物包裹在纳米囊泡中。从外部和内部来看，混合纳米囊泡的这些成分协同作用，从细胞外和细胞内的角度解决伤口愈合问题。囊泡-细胞融合时，外部的拉链部分促进细胞-细胞连接，内部的DNAzyme信号输出部分在监测炎症反应时起到阻碍作用。释放的积雪草苷具有促进细胞增殖、促进血管生成、加速细胞迁移/粘附、促进创面愈合等作用，具有抗氧化和抗溃疡的联合作用。研究表明，bhnv可以成功地加速伤口愈合和预防炎症。体外和体内均取得了良好的治疗效果，这表明局部伤口管理具有增强治疗效果的强大模式。

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引用次数: 0

3D culture reveals dual role of ICAM-1 in mediating tissue-specific human MSC spheroid formation & enhanced immunomodulation 三维培养揭示了ICAM-1在介导组织特异性人间充质干细胞球体形成和增强免疫调节中的双重作用

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-09 DOI: 10.1016/j.biomaterials.2026.123998

Li-Tzu Wang , Hsiu-Huan Wang , Duong Thi Thuy Doan , Yun-Fei Lin , Chien-Yu Liao , Pei-Ju Hsu , Chia-Chih Chang , Men-Luh Yen , Ko-Jiunn Liu , Huey-Kang Sytwu , B. Linju Yen

Three-dimensional (3D) in vitro culture systems may better mimic in vivo physiological conditions, and are easily accessible methods to improve therapeutic effectiveness of human mesenchymal stem cells (MSCs), which with its many sources appear to harbor clinically relevant functional differences. We therefore investigated the impact and elucidated the mechanism(s) of 3D culture on the immunomodulatory capacity of two commonly used MSC sources, bone marrow (BM) and placental (P). In 3D conditions, PMSCs (PMSC 3D) form larger spheroids than BMMSCs (BMMSC 3D), with whole transcriptome profiling revealing significant enrichment of cell adhesion and immunomodulatory pathways. qPCR and functional validation demonstrated the highest expression of numerous key immunomodulatory factors and strongest capacity to inhibit T cell proliferation with PMSC 3D. Bioinformatics analyses predicted Intercellular Adhesion Molecule 1 (ICAM-1) as crucial for both PMSC 3D spheroid formation and enhanced immunomodulatory capacity, which was validated with flow cytometric analyses and further delineated with single-cell RNA sequencing data. To assess mechanistic involvement, we performed knockdown of ICAM-1 which significantly reduced PMSC 3D spheroid size as well as both in vitro and in vivo immunomodulatory capacity. These findings demonstrate that 3D culture significantly enhances the immunomodulatory potential of PMSCs, and reveal ICAM-1 as having a dual role in spheroid formation as well as modulation of immune responses. Our study also highlights the importance of understanding source-specific differences as well as the profound influence of 3D in vitro systems on MSC functions.

三维（3D）体外培养系统可以更好地模拟体内生理条件，并且是提高人间充质干细胞（MSCs）治疗效果的容易获得的方法，其来源众多，似乎具有临床相关的功能差异。因此，我们研究了3D培养对骨髓（BM）和胎盘(P)两种常用的间充质干细胞来源的免疫调节能力的影响并阐明了其机制。在3D条件下，PMSCs （PMSC 3D）形成比BMMSCs （BMMSC 3D）更大的球体，全转录组分析显示细胞粘附和免疫调节途径显著富集。qPCR和功能验证表明，PMSC 3D中多种关键免疫调节因子的表达量最高，抑制T细胞增殖的能力最强。生物信息学分析预测细胞间粘附分子1 （ICAM-1）对于PMSC 3D球体形成和增强的免疫调节能力至关重要，这一点通过流式细胞分析和单细胞RNA测序数据得到了验证。为了评估机制参与，我们进行了ICAM-1的敲低，这显着降低了PMSC 3D球体大小以及体外和体内的免疫调节能力。这些发现表明，3D培养显著增强了PMSCs的免疫调节潜能，并揭示了ICAM-1在球状体形成和免疫反应调节中具有双重作用。我们的研究还强调了理解来源特异性差异的重要性，以及3D体外系统对MSC功能的深远影响。

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引用次数: 0

Harnessing the HMnO2 nanoparticles as the DNA injury amplifier to improve the OXA-based trans-artery infusion chemotherapy 利用HMnO2纳米颗粒作为DNA损伤放大器改善基于oxa的经动脉灌注化疗

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-08 DOI: 10.1016/j.biomaterials.2026.123993

Xianting Sun , Cai Feng , Zongling Xiong , Yifei Yang , Hao Zhou , Tianming Wang , Xiaofen Wang , Shulin Liu , Sai Li , Peng Lei , Liangrong Shi , Weihua Liao

Oxaliplatin (OXA) serves as a key chemotherapeutic agent in trans-arterial infusion chemotherapy (TAIC) for liver cancer. However, its clinical efficacy is frequently limited by several factors: suboptimal tumor uptake, systemic detoxification mediated by glutathione (GSH), and the activation of cellular DNA repair mechanisms. Herein, we present a hollow MnO₂ nanoparticle loaded with OXA, the PEI-HMnO₂@OXA, to improve the TAIC effect of OXA. The acidic tumor microenvironment facilitated the release of OXA and triggered PEI-HMnO₂ to generate free radicals. When coupled with GSH depletion, this cascade culminated in significant DNA damage. Moreover, the PEI-HMnO₂ showed a synergistic effect with OXA by blocking multiple DNA repair genes. On the other hand, by leveraging the enhanced permeability and retention effect of the nano-sized structure, 10–100 times greater tumor uptake and a more pronounced inhibitory effect by TAIC are achieved compared with intravenous or single-drug treatment. Meanwhile, the PEI-HMnO₂@OXA enabled real-time MRI monitoring of drug distribution and tumor state, facilitating the treatment guidance. Comprehensive experiments using different cell lines, mouse and rabbit models, and patient-derived HCC OXA-sensitive/resistant organoids were conducted to clarify the tumor-inhibiting effects of PEI-HMnO₂@OXA, providing novel insights into cancer management.

奥沙利铂（OXA）是肝癌经动脉输注化疗（TAIC）的关键化疗药物。然而，其临床疗效经常受到以下几个因素的限制：肿瘤摄取欠佳、谷胱甘肽（GSH）介导的全身解毒以及细胞DNA修复机制的激活。在此，我们提出了一种空心二氧化锰纳米颗粒，负载氧化钙PEI-HMnO2@OXA，以改善氧化钙的TAIC效果。酸性肿瘤微环境促进OXA的释放，触发PEI-HMnO2产生自由基。当与谷胱甘肽耗竭相结合时，这种级联反应最终导致显著的DNA损伤。此外，PEI-HMnO2通过阻断多个DNA修复基因与OXA表现出协同作用。另一方面，利用纳米级结构增强的渗透性和滞留效应，与静脉或单药治疗相比，TAIC的肿瘤摄取量增加10-100倍，抑制效果更明显。同时，PEI-HMnO2@OXA实现了对药物分布和肿瘤状态的实时MRI监测，便于治疗指导。利用不同细胞系、小鼠和兔子模型以及患者来源的肝癌oxa敏感/耐药类器官进行综合实验，以阐明PEI-HMnO2@OXA的肿瘤抑制作用，为癌症治疗提供新的见解。

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引用次数: 0

A biomietic filamentous hydrogel with enhanced bacteria contact and bactericidal efficiency for the treatment of various skin infections 一种具有增强细菌接触和杀菌效率的仿生丝状水凝胶，用于治疗各种皮肤感染

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-07 DOI: 10.1016/j.biomaterials.2025.123968

Yongchang Tian , Rong Zhang , Xingjun Zhao , Ian W. Hamley , Chunsheng Xiao , Li Chen

Antimicrobial hydrogels that can effectively eliminate microorganisms to accelerate wound healing have demostrated great potential in managing wound infections. However, conventional hydrogel dressings have limited contact with bacteria due to their permemnent cross-linked structure, thereby reducing their bactericidal efficiency. To address this issue, we designed and prepared a neutrophil extracellular traps (NETs) biomimetic antibacterial hydrogel (PETP gel) with enhanced bacteria contact and bactericidal efficiency through Schiff base crosslinking of antibacterial polymer PETP-NH₂ and phenylboronic acid functionalized oxidized hyaluronic acid (OHA-PBA). The obtained PETP gel exhibited a NETs-mimicking dynamic filamentous network structure, which, in combination with the interaction between phenylboronic acid in OHA-PBA and lipopolysaccharides in bacterial surface, ultimately led to enhanced bacteria contact and bactericidal efficiency. In vivo experiments showed that PETP gel could accelerate healing in treatment of purulent subcutaneous infection, full-thickness wound infection, and deep second-degree burn infection, showing promising use as an antibacterial care dressing.

抗菌水凝胶可以有效地消除微生物，加速伤口愈合，在处理伤口感染方面显示出巨大的潜力。然而，传统的水凝胶敷料由于其永久的交联结构，与细菌的接触有限，从而降低了其杀菌效率。为了解决这一问题，我们通过抗菌聚合物PETP- nh2和苯基硼酸功能化氧化透明质酸（OHA-PBA）的希夫碱交联，设计并制备了一种增强细菌接触和杀菌效率的中性细胞胞外捕集器（NETs）仿生抗菌水凝胶（PETP凝胶）。得到的PETP凝胶具有模拟nets的动态丝状网络结构，结合OHA-PBA中的苯硼酸与细菌表面脂多糖的相互作用，最终增强了细菌接触和杀菌效率。体内实验表明，PETP凝胶在治疗化脓性皮下感染、全层创面感染和深度二度烧伤感染中具有加速愈合的作用，作为抗菌护理敷料具有广阔的应用前景。

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引用次数: 0

Stripping cell-free DNA from its immune complex is essential for inflammation control using DNase I 从免疫复合体中剥离无细胞DNA对于使用DNA酶I控制炎症至关重要。

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-06 DOI: 10.1016/j.biomaterials.2026.123992

Shi Chen , Yibo Du , Chenxu Zhu , Chuang Li , Xingliang Liu , Lixin Liu , Yongming Chen

Excessive accumulation of cell-free DNA (cfDNA) has been identified as a primary pathogenic factor in autoimmune diseases. The circulating deoxyribonuclease (DNase) maintaining cfDNA homeostasis is suppressed, and thus exogenous DNase has been applied to degrade cfDNA for inflammation control. However, in pathological states, cfDNA and cationic endogenous peptide (e.g., LL37) form immune complexes (ICs), which not only weaken DNase efficacy but also facilitate immune cell internalization to induce an inflammatory response. With LL37-DNA as a model IC, here we found that the LL37 occupancy not only sterically hinders cfDNA's access to the catalytic sites but also induces deactivation of DNase via formation of ternary complexes (LL37-DNA-DNase I). This transition critically impairs the activity of DNase I within LL37-rich inflammatory microenvironments. Thus, we postulated that heparin, a clinically approved anionic glycosaminoglycan, could destruct the ICs and liberate cfDNAs, restoring their susceptibility to degradation. Indeed, we found that a combination of heparin and DNase I facilitates the DNA degradation and inhibits the ICs-mediated TLR9 activation in vitro. However, the therapeutic outcome observed in rheumatoid arthritis (RA) model was still suboptimal, attributed to the short plasma half-life of DNase. To validate this, we engineered a DNase nanoparticle (DNase@TANP) capable of sustained release of the enzyme. Consequently, the sequential administration of heparin and DNase@TANP (with a 30-min interval) to RA model demonstrated a synergistic cfDNA degradation efficiency, effectively suppressing Toll-like receptor (TLR) mediated inflammatory pathways and ameliorating joint inflammation. This strategy, leveraging clinically approved agents for cfDNA clearance, establishes a promising therapeutic paradigm for cfDNA-associated autoimmune disorders.

游离DNA （cfDNA）的过度积累已被确定为自身免疫性疾病的主要致病因素。维持cfDNA稳态的循环脱氧核糖核酸酶（循环脱氧核糖核酸酶）被抑制，因此外源性dna酶被用于降解cfDNA以控制炎症。然而，在病理状态下，cfDNA与阳离子内源性肽（如LL37）形成免疫复合物（ic），不仅削弱DNase的功效，而且促进免疫细胞内化，诱导炎症反应。以LL37- dna为模型IC，我们发现LL37的占用不仅在空间上阻碍cfDNA进入催化位点，而且通过形成三元配合物（LL37- dna -DNase I）诱导dna酶失活。这种转变严重损害了富含ll37的炎症微环境中DNase I的活性。因此，我们假设肝素，一种临床批准的阴离子糖胺聚糖，可以破坏ic并释放cfdna，恢复其降解易感性。事实上，我们发现肝素和DNA酶I的结合促进了DNA降解，并抑制了ics介导的TLR9的体外激活。然而，在类风湿关节炎（RA）模型中观察到的治疗结果仍然不理想，这是由于dna酶的血浆半衰期较短。为了验证这一点，我们设计了一种能够持续释放酶的dna酶纳米颗粒（DNase@TANP）。因此，依次给药肝素和DNase@TANP（间隔30分钟）对RA模型显示协同cfDNA降解效率，有效抑制toll样受体（TLR）介导的炎症途径并改善关节炎症。该策略利用临床批准的cfDNA清除药物，为cfDNA相关自身免疫性疾病建立了一个有希望的治疗范例。

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引用次数: 0

Self-assembled microparticle hydrogel scaffolds to construct artificial tertiary lymphoids for enhanced CAR-T cell therapy against solid tumors 自组装微粒水凝胶支架构建人工三级淋巴细胞用于增强CAR-T细胞治疗实体肿瘤

IF 12.9 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2026-01-06 DOI: 10.1016/j.biomaterials.2025.123976

Qiaofeng Li , Zhisheng Xiao , Bo Liu , Yuchun Xu , Chunjie Wang , Mingkang Li , Yuzhe Wu , Chenxi Yin , Wenzhuo Yu , Zhuang Liu , Yu Chao

Chimeric antigen receptor (CAR)-T cell therapy while demonstrating remarkable efficacies in treating hematologic malignancies, has encountered challenges in solid tumor treatment, partly due to the limited intratumoral infiltration of effective immune cells and thus inefficient interactions between different immune cell types inside those tumors. Herein, we develop an injectable scaffold based on hydrogel microparticles (HMPs) with opposite charges to replicate tertiary lymphoid structures (TLSs) within the tumor microenvironment. With encapsulation of immune-stimulating cytokines inside HMPs and loading of both T cells and B cells between HMPs in the scaffold, the artificial TLSs after intratumoral injection could not only serve as a depot of immunostimulants, but also promote intercellular interactions between B and T lymphocytes to support continuous T cell expansion and activation. As demonstrated in several tumor models, our artificial TLSs loaded with both CAR-T cells and B cells after intratumoral injection could not only effectively suppress local tumors, but also present remarkable abscopal effects to inhibit distant tumors, presenting greatly enhanced therapeutic performance compared to conventional CAR-T therapy. Our work thus presents a novel strategy to improve the efficacy of T-cell-therapies against solid tumors based on immune-activating cell-loaded injectable hydrogel scaffold as artificial TLSs.

嵌合抗原受体(CAR)-T细胞疗法虽然在治疗血液系统恶性肿瘤方面表现出显著的疗效，但在实体肿瘤治疗中遇到了挑战，部分原因是肿瘤内有效免疫细胞的浸润有限，因此肿瘤内不同免疫细胞类型之间的相互作用效率低下。在此，我们开发了一种基于具有相反电荷的水凝胶微粒（HMPs）的可注射支架，用于在肿瘤微环境中复制三级淋巴结构（TLSs）。通过将免疫刺激细胞因子包封在HMPs内，并将T细胞和B细胞装载在支架内的HMPs之间，瘤内注射后的人工TLSs不仅可以作为免疫刺激物的储存库，还可以促进B和T淋巴细胞之间的细胞间相互作用，支持T细胞的持续扩增和活化。多个肿瘤模型表明，我们的人工TLSs在瘤内注射同时装载CAR-T细胞和B细胞后，不仅能有效抑制局部肿瘤，而且对远处肿瘤也有明显的体外抑制作用，与常规CAR-T治疗相比，治疗效果大大提高。因此，我们的工作提出了一种新的策略来提高基于免疫激活细胞负载的可注射水凝胶支架作为人工TLSs的t细胞治疗对实体瘤的疗效。

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引用次数: 0