Bioactive Materials最新文献_第5页

Divalent metal ions enhance bone regeneration through modulation of nervous systems and metabolic pathways

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-02-12 DOI: 10.1016/j.bioactmat.2025.01.034

Ying Luo , Baoyi Liu , Yashi Qiu , Lichen Li , Fan Yang , Chao Zhang , Jiali Wang

The divalent metal cations promote new bone formation through modulation of sensory and sympathetic nervous systems (SNS) activities. In addition, acetylcholine (Ach), as a chief neurotransmitter released by the parasympathetic nervous system (PNS), also affects bone remodeling, so it is of worth to investigate if the divalent cations influence PNS activity. Of note, these cations are key co-enzymes modulating glucose metabolism. Aerobic glycolysis rather than oxidative phosphorylation favors osteogenesis of mesenchymal stem cells (MSCs), so it is of interest to study the effects of these cations on glucose metabolic pathway. Prior to biological function assessment, the tolerance limits of the divalent metal cations (Mg²⁺, Zn²⁺, and Ca²⁺) and their combinations were profiled. In terms of direct effects, these divalent cations potentially enhanced migration and adhesion capability of MSCs through upregulating Tgf-β1 and Integrin-β1 levels. Interestingly, the divalent cations alone did not influence osteogenesis and aerobic glycolysis of undifferentiated MSCs. However, once the osteogenic differentiation of MSCs was initiated by neurotransmitters or osteogenic differentiation medium, the osteogenesis of MSCs could be significantly promoted by the divalent cations, which was accompanied by the improved aerobic glycolysis. In terms of indirect effects, the divalent cations significantly upregulated levels of sensory nerve derived CGRP, PNS produced choline acetyltransferase and type H vessels, while significantly tuned down sympathetic activity in the defect zone in rats, thereby contributing to significantly increased bone formation relative to the control group. Together, the divalent cations favor bone regeneration via modulation of sensory-autonomic nervous systems and promotion of aerobic glycolysis-driven osteogenesis of MSCs after osteogenic initiation by neurotransmitters.

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引用次数: 0

Dental pulp stem cells alleviate Schwann cell pyroptosis via mitochondrial transfer to enhance facial nerve regeneration

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-02-11 DOI: 10.1016/j.bioactmat.2025.01.031

Xiaoyu Zheng , Juan Wang , Heng Zhou , Ying Chai , Ziwei Li , Minjie Chen , Zihan Yang , Chun Xu , Chang Lei , Yan He , Duohong Zou , Qingsong Ye

Dental pulp stem cells (DPSCs) have demonstrated remarkable potential in enhancing peripheral nerve regeneration, though the precise mechanisms remain largely unknown. This study investigates how DPSCs alleviate Schwann cell pyroptosis and restore mitochondrial homeostasis through intercellular mitochondrial transfer. In a crab-eating macaque model, we first observed that DPSC-loaded nerve conduits significantly promoted long-term nerve regeneration, facilitating tissue proliferation and myelin recovery. We further established a rat facial nerve injury (FNI) model and found that DPSC treatment reduced pyroptosis and mitochondrial ROS production in Schwann cells. A pivotal mitochondrial protective mechanism, resembling the effects of a ROS-targeted inhibitor, involved the transfer of mitochondria from DPSCs to pyroptosis-induced Schwann cells via tunneling nanotubes, while blocking intercellular junctions or mitochondrial function diminished the therapeutic effects. TNFα secreted by pyroptosis-induced Schwann cells activated the NF-κB pathway in DPSCs, enhancing mitochondrial transfer and adaptive stress responses, thereby promoting mitochondrial protection against pyroptosis in Schwann cells, as reflected in the improved therapeutic efficacy of TNFα-preconditioned DPSCs in the FNI model. These findings unveil a mechanism through which DPSCs foster nerve regeneration via mitochondrial transfer, presenting a promising strategy for enhancing stem cell-based therapies for nerve injuries.

{"title":"Dental pulp stem cells alleviate Schwann cell pyroptosis via mitochondrial transfer to enhance facial nerve regeneration","authors":"Xiaoyu Zheng , Juan Wang , Heng Zhou , Ying Chai , Ziwei Li , Minjie Chen , Zihan Yang , Chun Xu , Chang Lei , Yan He , Duohong Zou , Qingsong Ye","doi":"10.1016/j.bioactmat.2025.01.031","DOIUrl":"10.1016/j.bioactmat.2025.01.031","url":null,"abstract":"<div><div>Dental pulp stem cells (DPSCs) have demonstrated remarkable potential in enhancing peripheral nerve regeneration, though the precise mechanisms remain largely unknown. This study investigates how DPSCs alleviate Schwann cell pyroptosis and restore mitochondrial homeostasis through intercellular mitochondrial transfer. In a crab-eating macaque model, we first observed that DPSC-loaded nerve conduits significantly promoted long-term nerve regeneration, facilitating tissue proliferation and myelin recovery. We further established a rat facial nerve injury (FNI) model and found that DPSC treatment reduced pyroptosis and mitochondrial ROS production in Schwann cells. A pivotal mitochondrial protective mechanism, resembling the effects of a ROS-targeted inhibitor, involved the transfer of mitochondria from DPSCs to pyroptosis-induced Schwann cells via tunneling nanotubes, while blocking intercellular junctions or mitochondrial function diminished the therapeutic effects. TNFα secreted by pyroptosis-induced Schwann cells activated the NF-κB pathway in DPSCs, enhancing mitochondrial transfer and adaptive stress responses, thereby promoting mitochondrial protection against pyroptosis in Schwann cells, as reflected in the improved therapeutic efficacy of TNFα-preconditioned DPSCs in the FNI model. These findings unveil a mechanism through which DPSCs foster nerve regeneration via mitochondrial transfer, presenting a promising strategy for enhancing stem cell-based therapies for nerve injuries.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 313-326"},"PeriodicalIF":18.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Natural potential difference induced functional optimization mechanism for Zn-based multimetal bone implants 自然电位差诱导锌基多金属骨植入物功能优化机制。

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-02-01 DOI: 10.1016/j.bioactmat.2024.10.030

Jing Xu , Zhenbao Zhang , Jianhui Wang , Yuhan Qi , Xiaohong Qi , Yijie Liang , Manxi Li , Haixia Li , Yantao Zhao , Zhuangzhuang Liu , Yanfeng Li

Zn-based biodegradable metals (BMs) are regarded as revolutionary biomaterials for bone implants. However, their clinical application is limited by insufficient mechanical properties, delayed in vivo degradation, and overdose-induced Zn²⁺ toxicity. Herein, innovative multi-material additive manufacturing (MMAM) is deployed to construct a Zn/titanium (Ti) hetero-structured composite. The biodegradation and biofunction of Zn exhibited intriguing characteristics in composites. A potential difference of about 300 mV naturally existed between Zn and Ti. This natural potential difference triggered galvanic coupling corrosion, resulting in 2.7 times accelerated degradation of Zn. The excess release of Zn²⁺ induced by accelerated degradation enhanced the antibacterial function. A voltage signal generated by the natural potential difference also promoted in vitro osteogenic differentiation through activating the PI3K-Akt signaling pathway, and inhibited the toxicity of overdose Zn²⁺ in vivo, significantly improving bone regeneration. Furthermore, MMAM technology allows for the specific region deployment of components. In the future, Ti and Zn could be respectively deployed in the primary and non-load-bearing regions of bone implants by structural designs, thereby achieving a functionally graded application to overcome the insufficient mechanical properties of Zn-based BMs. This work clarifies the functional optimization mechanism for multimetal bone implants, which possibly breaks the application dilemma of Zn-based BMs.

锌基生物可降解金属（BMs）被认为是一种革命性的骨植入材料。然而，它们的临床应用受到力学性能不足、体内降解延迟和过量诱导Zn2+毒性的限制。本文采用创新的多材料增材制造技术（MMAM）构建了锌/钛（Ti）异质结构复合材料。锌在复合材料中的生物降解和生物功能表现出有趣的特征。锌和钛之间自然存在约300毫伏的电位差。这种自然电位差引发电偶腐蚀，导致Zn的降解加速2.7倍。加速降解诱导Zn2+的过量释放增强了抗菌功能。自然电位差产生的电压信号也通过激活PI3K-Akt信号通路促进体外成骨分化，抑制体内过量Zn2+的毒性，显著促进骨再生。此外，MMAM技术允许在特定区域部署组件。在未来，通过结构设计，Ti和Zn可以分别部署在骨种植体的主要和非承重区域，从而实现功能分级应用，以克服锌基脑转移物力学性能不足的问题。本研究阐明了多金属骨植入物的功能优化机制，有望打破锌基骨植入物的应用困境。

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引用次数: 0

Editor's note 勘误：编者注。

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-02-01 DOI: 10.1016/j.bioactmat.2024.06.033

引用次数: 0

An ultrasound-driven PLGA/Zn-KNN hybrid piezoelectric scaffold with direct and immunoregulatory antibacterial activity for bone infection

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-01-27 DOI: 10.1016/j.bioactmat.2025.01.026

Yuhao Zheng , Shu Wang , Wenhe Jin , Zhuoxuan Li , Guoju Yang , Xiaoxu Li , Ning Li , Yue Wang , Fan Sheng , Zhiming Song

Antibacterial piezoelectric materials have broad application prospects in the medical field because of their broad-spectrum antibacterial properties and no bacterial drug resistance. At present, one of the main problems in the application of piezoelectric materials is the low electrocatalytic efficiency, which limits its application in antibacterial field. In this study, a piezoelectric antibacterial (PLGA/Zn-KNN) scaffold was fabricated by incorporating zinc oxide (ZnO) into potassium-sodium niobate (KNN) and composited with a poly (lactic-co-glycolic acid) (PLGA) to achieve multicombination antibacterial for bone infection. The physicochemical properties of piezoelectric antibacterial scaffolds were analyzed. Bacterial, cell, and animal experiments were performed to characterize the antibacterial and infection treatment capabilities of piezoelectric scaffolds. The piezoelectric properties of the PLGA/Zn-KNN scaffold were enhanced by embedding ZnO particles into the KNN solid solution matrix. Furthermore, the piezoelectric scaffold released zinc ions, and electrical stimulation driven by ultrasound resulted in significant antibacterial effects through direct and immunoregulatory antibacterial pathways. Mechanistic investigation suggested that extracellular matrix ligands and complement and coagulation cascades may have a moderate effect on macrophage phagocytosis. This work highlights potential application methods for fabricating novel antibacterial hybrid piezoelectric scaffolds and engineering macrophages with immunoregulatory antibacterial activity.

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引用次数: 0

Engineered bacterial membrane biomimetic covalent organic framework as nano-immunopotentiator for cancer immunotherapy

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-01-25 DOI: 10.1016/j.bioactmat.2025.01.018

Qi-Chao Yang, Yuan-Yuan Wang, Shuo Wang, An Song, Wen-Da Wang, Liang Zhang, Zhi-Jun Sun

The cellular uptake and tissue dispersion efficiency of nanomedicines are crucial for realizing their biological functionality. As a cutting-edge category of nanomedicine, covalent organic frameworks (COFs)-based photosensitizers, have been extensively employed in cancer phototherapy in recent years. However, the inherent aggregation tendency of COFs hinders their uptake by tumor cells and dispersion within tumor tissues, thereby limiting their therapeutic efficacy. In this study, we employed Fusobacterium nucleatum (F.n.), a prevalent intratumoral bacterium, to construct a bacterium membrane-wrapped COF, COF-306@FM, which is readily taken up by cancer cells and uniformly dispersed within tumor tissues. Meanwhile, the F.n. membrane can also serve as an immune adjuvant to warm up the “cold” tumor immune microenvironment by enhancing the CD8⁺ T and B cells infiltration, and inducing the formation of tumor-located tertiary lymphoid structures. Consequently, the response rate of αPD-L1 immunotherapy was drastically promoted to efficiently prevent tumor metastasis and recurrence, causing 84.6 % distant tumor inhibition and complete suppression of tumor metastasis. In summary, this innovative approach not only enhances the therapeutic potential of COFs but also opens up new avenues for integrating microbial and nanotechnological strategies in cancer treatment.

{"title":"Engineered bacterial membrane biomimetic covalent organic framework as nano-immunopotentiator for cancer immunotherapy","authors":"Qi-Chao Yang, Yuan-Yuan Wang, Shuo Wang, An Song, Wen-Da Wang, Liang Zhang, Zhi-Jun Sun","doi":"10.1016/j.bioactmat.2025.01.018","DOIUrl":"10.1016/j.bioactmat.2025.01.018","url":null,"abstract":"<div><div>The cellular uptake and tissue dispersion efficiency of nanomedicines are crucial for realizing their biological functionality. As a cutting-edge category of nanomedicine, covalent organic frameworks (COFs)-based photosensitizers, have been extensively employed in cancer phototherapy in recent years. However, the inherent aggregation tendency of COFs hinders their uptake by tumor cells and dispersion within tumor tissues, thereby limiting their therapeutic efficacy. In this study, we employed <em>Fusobacterium nucleatum</em> (<em>F.n</em>.), a prevalent intratumoral bacterium, to construct a bacterium membrane-wrapped COF, COF-306@FM, which is readily taken up by cancer cells and uniformly dispersed within tumor tissues. Meanwhile, the <em>F.n.</em> membrane can also serve as an immune adjuvant to warm up the “cold” tumor immune microenvironment by enhancing the CD8<sup>+</sup> T and B cells infiltration, and inducing the formation of tumor-located tertiary lymphoid structures. Consequently, the response rate of αPD-L1 immunotherapy was drastically promoted to efficiently prevent tumor metastasis and recurrence, causing 84.6 % distant tumor inhibition and complete suppression of tumor metastasis. In summary, this innovative approach not only enhances the therapeutic potential of COFs but also opens up new avenues for integrating microbial and nanotechnological strategies in cancer treatment.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 283-294"},"PeriodicalIF":18.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endogenous electric field-driven neuro-immuno-regulatory scaffold for effective diabetic wound healing

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-01-25 DOI: 10.1016/j.bioactmat.2025.01.024

Zhiqing Liu , Tianlong Wang , Jinhui Zhao , Lei Zhang , Yiping Luo , Yixing Chen , Xinhui Wu , Yaqi Liu , Aihemaitijiang Aierken , Dilixiati Duolikun , Hui Jiang , Xinyu Zhao , Chang Li , Yingchuan Li , Wentao Cao , Jianzhong Du , Longpo Zheng

The pathological microenvironment in diabetic wounds is delineated by heightened inflammatory responses and persistent proinflammatory macrophage activity, which significantly hinders the wound healing process. Exogenous electrical stimulation (ES), by modulating the electric field distribution in wounds, has shown significant potential in treating inflammatory wounds. However, this approach relies on additional power sources and complex circuit designs. Here, a bionic neuro-immuno-regulatory (BNIR) system was proposed for reshaping the endogenous electric fields (EFs) through collecting ion flow. The BNIR system comprises microporous structure scaffolds and nanosheets, enabling swift biofluid collection and electrical signal transmission, with the ability to promote cell proliferation and migration and exhibit antioxidant properties. More importantly, the BNIR system induced the transition of M1 macrophages to M2 macrophages through neuro-immuno-regulatory. In diabetic rat skin wounds, the BNIR system significantly enhanced healing by simultaneously neuro-immuno-regulatory, promoting angiogenesis, scavenging ROS, and facilitating tissue remodeling. This work aims to advance the development of a bionic system for electrosensitive tissue repair.

{"title":"Endogenous electric field-driven neuro-immuno-regulatory scaffold for effective diabetic wound healing","authors":"Zhiqing Liu , Tianlong Wang , Jinhui Zhao , Lei Zhang , Yiping Luo , Yixing Chen , Xinhui Wu , Yaqi Liu , Aihemaitijiang Aierken , Dilixiati Duolikun , Hui Jiang , Xinyu Zhao , Chang Li , Yingchuan Li , Wentao Cao , Jianzhong Du , Longpo Zheng","doi":"10.1016/j.bioactmat.2025.01.024","DOIUrl":"10.1016/j.bioactmat.2025.01.024","url":null,"abstract":"<div><div>The pathological microenvironment in diabetic wounds is delineated by heightened inflammatory responses and persistent proinflammatory macrophage activity, which significantly hinders the wound healing process. Exogenous electrical stimulation (ES), by modulating the electric field distribution in wounds, has shown significant potential in treating inflammatory wounds. However, this approach relies on additional power sources and complex circuit designs. Here, a bionic neuro-immuno-regulatory (BNIR) system was proposed for reshaping the endogenous electric fields (EFs) through collecting ion flow. The BNIR system comprises microporous structure scaffolds and nanosheets, enabling swift biofluid collection and electrical signal transmission, with the ability to promote cell proliferation and migration and exhibit antioxidant properties. More importantly, the BNIR system induced the transition of M1 macrophages to M2 macrophages through neuro-immuno-regulatory. In diabetic rat skin wounds, the BNIR system significantly enhanced healing by simultaneously neuro-immuno-regulatory, promoting angiogenesis, scavenging ROS, and facilitating tissue remodeling. This work aims to advance the development of a bionic system for electrosensitive tissue repair.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 266-282"},"PeriodicalIF":18.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CD9-enriched extracellular vesicles from chemically reprogrammed basal progenitors of salivary glands mitigate salivary gland fibrosis

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-01-24 DOI: 10.1016/j.bioactmat.2025.01.019

Sunyoung Park , Yeo-Jun Yoon , Yongpyo Hong , Jianning Yu , Jae-Min Cho , Ye Jin Jeong , Haeun Yu , Hyorim Jeong , Hyunjin Lee , Seungyeon Hwang , Won-Gun Koh , Ji Yeong Yang , Kyung-A Hyun , Hyo-Il Jung , Jae-Yol Lim

Extracellular vesicles (EVs) derived from stem cells offer promising potential for cell-free therapy. However, refining their cargo for precise disease targeting and delivery remains challenging. This study employed chemical reprogramming via dual inhibition of transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP) to expand salivary gland basal progenitor cells (sgBPCs). CD9-enriched (CD9⁺) EVs were then isolated from the sgBPC secretome concentrate using a dual microfluidic chip. Notably, CD9⁺ EVs demonstrated superior uptake by salivary epithelial cells compared to CD9-depleted (CD9⁻) EVs and total EVs. In vivo studies using a salivary gland (SG) obstruction mouse model and ex vivo studies in SG fibrosis organoids revealed that CD9⁺ EVs significantly enhanced anti-fibrotic effects over CD9⁻ EVs and control treatments. The presence of miR-3162 and miR-1290 in CD9⁺ EVs supported their anti-fibrotic properties by downregulating ACVR1 expression. The chemical reprogramming culture method effectively expanded sgBPCs, enabling consistent and scalable EV production. Utilizing microfluidic chip-isolated CD9⁺ EVs and ductal delivery presents a targeted and efficient approach for anti-fibrotic SG regeneration.

{"title":"CD9-enriched extracellular vesicles from chemically reprogrammed basal progenitors of salivary glands mitigate salivary gland fibrosis","authors":"Sunyoung Park , Yeo-Jun Yoon , Yongpyo Hong , Jianning Yu , Jae-Min Cho , Ye Jin Jeong , Haeun Yu , Hyorim Jeong , Hyunjin Lee , Seungyeon Hwang , Won-Gun Koh , Ji Yeong Yang , Kyung-A Hyun , Hyo-Il Jung , Jae-Yol Lim","doi":"10.1016/j.bioactmat.2025.01.019","DOIUrl":"10.1016/j.bioactmat.2025.01.019","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) derived from stem cells offer promising potential for cell-free therapy. However, refining their cargo for precise disease targeting and delivery remains challenging. This study employed chemical reprogramming via dual inhibition of transforming growth factor beta (TGFβ) and bone morphogenetic protein (BMP) to expand salivary gland basal progenitor cells (sgBPCs). CD9-enriched (CD9<sup>+</sup>) EVs were then isolated from the sgBPC secretome concentrate using a dual microfluidic chip. Notably, CD9<sup>+</sup> EVs demonstrated superior uptake by salivary epithelial cells compared to CD9-depleted (CD9<sup>−</sup>) EVs and total EVs. <em>In vivo</em> studies using a salivary gland (SG) obstruction mouse model and <em>ex vivo</em> studies in SG fibrosis organoids revealed that CD9<sup>+</sup> EVs significantly enhanced anti-fibrotic effects over CD9<sup>−</sup> EVs and control treatments. The presence of miR-3162 and miR-1290 in CD9<sup>+</sup> EVs supported their anti-fibrotic properties by downregulating ACVR1 expression. The chemical reprogramming culture method effectively expanded sgBPCs, enabling consistent and scalable EV production. Utilizing microfluidic chip-isolated CD9<sup>+</sup> EVs and ductal delivery presents a targeted and efficient approach for anti-fibrotic SG regeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 229-247"},"PeriodicalIF":18.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143135289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineered macrophage nanoparticles enhance microwave ablation efficacy in osteosarcoma via targeting the CD47-SIRPα Axis: A novel Biomimetic immunotherapeutic approach

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-01-24 DOI: 10.1016/j.bioactmat.2025.01.012

Xiongfa Ji , Xin Qian , Guowen Luo , Wenjie Yang , Wenhan Huang , Zehua Lei , Jiaqi Zhou , Guoqing Zhong , Jielong Zhou , Nan Liu , Limin Ma , Mei Li , Xiangmei Liu , Shuilin Wu , Yu Zhang

Osteosarcoma (OS) is a lethal bone tumor that primarily affects adolescents. OS is characterized by a high incidence of recurrence following surgical intervention, which is attributed to the presence of residual microscopic disease. Tumor-associated macrophages, which dominate the tumor microenvironment, often suppress immune responses and facilitate tumor progression and recurrence. This study developed an innovative nanotherapeutic approach by utilizing genetically engineered macrophage membranes with M1 polarization, stably overexpressing signal regulatory protein alpha (SIRPα), to encapsulate microwave-responsive nano-Prussian blue (SIRPα-M@nanoPB) nanoparticles. These nanoparticles induce tumor cell death selectively through hyperthermia and microwave dynamic effects upon targeted microwave irradiation. It is of critical importance to note that the enhancement of SIRPα on the nanoparticle surface actively targets and binds CD47 of tumor cells, thereby disrupting the "don't-eat-me" signal and effectively countering the immunosuppressive tumor environment. This action restores macrophage phagocytosis with M1 polarization, triggering potent immune responses. Our strategy holds considerable promise when it comes to improving the efficacy of microwave ablation through immune modulation, while reducing thermal damage to adjacent normal tissue and minimizing the risk of tumor recurrence. Thus, it offers a significant advancement in microwave therapies for patients with OS.

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引用次数: 0

Saliva-acquired pellicle inspired multifunctional gargle with wet adhesion, photodynamic antimicrobial, and In situ remineralization properties for dental caries prevention

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2025-01-23 DOI: 10.1016/j.bioactmat.2025.01.008

Jiayi Shi , Xuekai Qi , Ying Ran , Qiang Zhou , Yiqin Ding , Lujian Li , Youyun Zeng , Dongchao Qiu , Zhibin Cai , Xiaojun Cai , Yihuai Pan

Dental caries is primarily caused by cariogenic bacteria metabolizing carbohydrates to produce acidic substances that erode the dental hard tissues. Traditional remineralization treatments often have limited efficacy due to their lack of antibacterial activity. According to the Interrupting Dental Caries (IDC) theory, ideal caries-preventive materials should possess both antibacterial and remineralizing properties. Furthermore, effective adhesion to dental surfaces is crucial. Inspired by the wet adhesion properties of the salivary acquired pellicle, we developed a multifunctional gargle named Ce6@PDN-SAP (CP-SAP). This formulation employed peptide dendrimer nanogels (PDN) as a carrier for the photosensitizer Ce6, further functionalized with saliva-acquired peptide (SAP) to confer wet adhesion properties. CP-SAP rapidly adhered to the dental surface and remained effective for extended periods. Upon laser irradiation, Ce6 generated reactive oxygen species (ROS), disrupting bacterial outer membrane integrity, causing protein leakage, and reducing ATP levels, thereby achieving potent antibacterial effects. Following this, PDN and SAP acted as nucleation templates to promote in situ remineralization of demineralized dental hard tissues. In vivo studies using rat models demonstrated that CP-SAP provided significantly superior caries-preventive effects compared to chlorhexidine gargle. In conclusion, CP-SAP, as an innovative approach grounded in the IDC theory, holds great promise for the prevention and treatment of dental caries.

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引用次数: 0