Pub Date : 2025-02-12DOI: 10.1016/j.bioactmat.2024.09.027
Yanbing Kao , Wei Song , Renjie Zhang , Guangjin Gu , Heping Qiu , Wenyuan Shen , Hanming Zhu , Yanchun Liu , Yu Yang , Haoyun Liu , Zhihao Zhang , Xiaohong Kong , Shiqing Feng
Spinal cord injury (SCI) is a devastating disease with limited treatment options due to the restricted regenerative capacity of the central nervous system. The accumulation of reactive oxygen species (ROS) and inadequate endogenous neural stem progenitor cells (eNSPCs) in the lesion site exacerbates neurologic deficits and impedes motor function recovery. We have developed a temperature-responsive hyaluronic acid conjugated hydrogel-polydopamine nanoparticles (PDA NPs) combined with human mesenchymal stem cell (hMSCs) transplantation, denoted as H-P-M hydrogel. Microglia cells treated with PDA NPs have been shown to reduce intracellular ROS levels by 65 % and suppress the expression of inflammatory cytokines such as IL-1β (decreased by 35 %) and IL-6 (decreased by 23 %), thus mitigating the microglia's inflammatory response. Additionally, our results have demonstrated that the H-P-M hydrogel combined with hMSCs transplantation can recruit eNSPCs to the injury site as evidenced by utilizing Nestin lineage tracer mice. The RNA-seq has unveiled the potential of the H-P-M hydrogel to facilitate eNSPCs neuronal differentiation through the MAPK pathway. Furthermore, these differentiated neurons are integrated into local neural circuits. Together, it suggests that the H-P-M hydrogel synergistically improves the SCI niche. It serves as catalysts inducing 5-HT axon regeneration and improving BMS score after SCI through the modulation of the ROS milieu and the promotion of neuronal differentiation from eNSPCs, thereby presenting a promising strategy for SCI repair.
{"title":"Synergistic restoration of spinal cord injury through hyaluronic acid conjugated hydrogel-polydopamine nanoparticles combined with human mesenchymal stem cell transplantation","authors":"Yanbing Kao , Wei Song , Renjie Zhang , Guangjin Gu , Heping Qiu , Wenyuan Shen , Hanming Zhu , Yanchun Liu , Yu Yang , Haoyun Liu , Zhihao Zhang , Xiaohong Kong , Shiqing Feng","doi":"10.1016/j.bioactmat.2024.09.027","DOIUrl":"10.1016/j.bioactmat.2024.09.027","url":null,"abstract":"<div><div>Spinal cord injury (SCI) is a devastating disease with limited treatment options due to the restricted regenerative capacity of the central nervous system. The accumulation of reactive oxygen species (ROS) and inadequate endogenous neural stem progenitor cells (eNSPCs) in the lesion site exacerbates neurologic deficits and impedes motor function recovery. We have developed a temperature-responsive hyaluronic acid conjugated hydrogel-polydopamine nanoparticles (PDA NPs) combined with human mesenchymal stem cell (hMSCs) transplantation, denoted as H-P-M hydrogel. Microglia cells treated with PDA NPs have been shown to reduce intracellular ROS levels by 65 % and suppress the expression of inflammatory cytokines such as IL-1β (decreased by 35 %) and IL-6 (decreased by 23 %), thus mitigating the microglia's inflammatory response. Additionally, our results have demonstrated that the H-P-M hydrogel combined with hMSCs transplantation can recruit eNSPCs to the injury site as evidenced by utilizing Nestin lineage tracer mice. The RNA-seq has unveiled the potential of the H-P-M hydrogel to facilitate eNSPCs neuronal differentiation through the MAPK pathway. Furthermore, these differentiated neurons are integrated into local neural circuits. Together, it suggests that the H-P-M hydrogel synergistically improves the SCI niche. It serves as catalysts inducing 5-HT axon regeneration and improving BMS score after SCI through the modulation of the ROS milieu and the promotion of neuronal differentiation from eNSPCs, thereby presenting a promising strategy for SCI repair.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 569-581"},"PeriodicalIF":18.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394392","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}
Pub Date : 2025-02-12DOI: 10.1016/j.bioactmat.2025.01.029
Yujie Mu , Yanmei Wang , Lei Huang , Zhenzhen Weng , Tingting Zhong , Sisi Yu , Yiming Wen , Yingying Xu , Xiaolei Wang
Dental caries is one of the most prevalent chronic infectious diseases, mainly due to acid production by bacteria in the plaque biofilm, leading to enamel demineralization, tooth defects and pulpitis. Most of the current treatments are invasive and do not combine restoration of dental tissues, resolution of tooth staining or prevention of dental caries. In this study, a polydopamine (PDA)-encapsulated strontium-doped zinc oxide composite (Sr-ZnO@PDA, denoted as SZ@PDA) has been developed for caries prevention and remineralization. The PDA wrapping endows SZ@PDA with a narrow energy band gap (1.78 eV), which can simultaneously respond to yellow light (YL) with favorable biosafety and ultrasound (US) with high tissue penetration. The synergistic piezo-photocatalytic action of YL and US with the enhanced catalytic efficiency can generate an appropriate amount of reactive oxygen species (ROS), thus destroying the structure of bacterial cellular membranes and decomposing pigments for caries prevention and improvement of tooth staining, respectively. In addition, strontium ions (Sr2+) released by SZ@PDA, as an active element, can promote the remineralization of enamel and dentin, repairing defective dental tissues. Collectively, this versatile system (SZ@PDA) provides an effective strategy for the prevention and treatment of caries.
{"title":"Yellow light and ultrasound Dual-responsive strontium-doped zinc oxide composites for dental caries prevention and remineralization","authors":"Yujie Mu , Yanmei Wang , Lei Huang , Zhenzhen Weng , Tingting Zhong , Sisi Yu , Yiming Wen , Yingying Xu , Xiaolei Wang","doi":"10.1016/j.bioactmat.2025.01.029","DOIUrl":"10.1016/j.bioactmat.2025.01.029","url":null,"abstract":"<div><div>Dental caries is one of the most prevalent chronic infectious diseases, mainly due to acid production by bacteria in the plaque biofilm, leading to enamel demineralization, tooth defects and pulpitis. Most of the current treatments are invasive and do not combine restoration of dental tissues, resolution of tooth staining or prevention of dental caries. In this study, a polydopamine (PDA)-encapsulated strontium-doped zinc oxide composite (Sr-ZnO@PDA, denoted as SZ@PDA) has been developed for caries prevention and remineralization. The PDA wrapping endows SZ@PDA with a narrow energy band gap (1.78 eV), which can simultaneously respond to yellow light (YL) with favorable biosafety and ultrasound (US) with high tissue penetration. The synergistic piezo-photocatalytic action of YL and US with the enhanced catalytic efficiency can generate an appropriate amount of reactive oxygen species (ROS), thus destroying the structure of bacterial cellular membranes and decomposing pigments for caries prevention and improvement of tooth staining, respectively. In addition, strontium ions (Sr<sup>2+</sup>) released by SZ@PDA, as an active element, can promote the remineralization of enamel and dentin, repairing defective dental tissues. Collectively, this versatile system (SZ@PDA) provides an effective strategy for the prevention and treatment of caries.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 403-416"},"PeriodicalIF":18.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388136","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}
Pub Date : 2025-02-12DOI: 10.1016/j.bioactmat.2025.01.025
Yuli Zhao , Ting Wang , Jiajun Liu , Ze Wang , Yuan Lu
Brain organoids are an emerging in vitro 3D brain model that is integrated from pluripotent stem cells. This model mimics the human brain’s developmental process and disease-related phenotypes to a certain extent while advancing the development of human brain-based biological intelligence. However, many limitations of brain organoid culture (e.g., lacking a functional vascular system, etc.) prevent in vitro-cultured organoids from truly replicating the human brain in terms of cell type and structure. To improve brain organoids' scalability, efficiency, and stability, this paper discusses important contributions of material biology and microprocessing technology in solving the related limitations of brain organoids and applying the latest imaging technology to make real-time imaging of brain organoids possible. In addition, the related applications of brain organoids, especially the development of organoid intelligence combined with artificial intelligence, are analyzed, which will help accelerate the rational design and guidance of brain organoids.
{"title":"Emerging brain organoids: 3D models to decipher, identify and revolutionize brain","authors":"Yuli Zhao , Ting Wang , Jiajun Liu , Ze Wang , Yuan Lu","doi":"10.1016/j.bioactmat.2025.01.025","DOIUrl":"10.1016/j.bioactmat.2025.01.025","url":null,"abstract":"<div><div>Brain organoids are an emerging <em>in vitro</em> 3D brain model that is integrated from pluripotent stem cells. This model mimics the human brain’s developmental process and disease-related phenotypes to a certain extent while advancing the development of human brain-based biological intelligence. However, many limitations of brain organoid culture (e.g., lacking a functional vascular system, etc.) prevent <em>in vitro</em>-cultured organoids from truly replicating the human brain in terms of cell type and structure. To improve brain organoids' scalability, efficiency, and stability, this paper discusses important contributions of material biology and microprocessing technology in solving the related limitations of brain organoids and applying the latest imaging technology to make real-time imaging of brain organoids possible. In addition, the related applications of brain organoids, especially the development of organoid intelligence combined with artificial intelligence, are analyzed, which will help accelerate the rational design and guidance of brain organoids.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 378-402"},"PeriodicalIF":18.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387977","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}
Pub Date : 2025-02-12DOI: 10.1016/j.bioactmat.2024.12.027
Fuxiao Wang , Yafei Han , Qirong Zhou , Shihao Sheng , Yan Hu , Hao Zhang , Xiao Chen , Chongru He , Hongbo Tan , Long Bai , Jiacan Su
Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to joint deformities and functional impairments. Traditional treatment approaches, such as nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and molecular targeted therapies, often fail to simultaneously achieve efficient inflammation relief and cartilage tissue repair. DNA hydrogels, derived from nucleic acid nanotechnology, have demonstrated potential in RA therapy due to their programmability, high biocompatibility, and tunable degradation properties. However, their application is still hindered by challenges including high synthesis costs, immunogenicity risks, and uncontrolled degradation rates. To address these limitations, this study proposes a dual-action strategy involving a polymer-modified DNA hydrogel co-delivering nanozymes and living mitochondria to overcome the constraints of traditional therapies and comprehensively optimize RA treatment outcomes. The incorporation of functionalized polymers significantly reduces synthesis costs and immunogenicity while fine-tuning the degradation rate of the hydrogel, enabling sustained support during bone and cartilage repair. The hydrogel is loaded with Prussian blue nanozymes to scavenge excessive reactive oxygen species (ROS) within the RA microenvironment, alleviating inflammation, and facilitates intracellular delivery of living mitochondria to inhibit ROS production at its source, promoting tissue repair. By integrating endogenous ROS reduction with exogenous ROS clearance, this strategy markedly enhances therapeutic efficacy, offering a novel approach for precise RA treatment and advancing the clinical translation of biomaterials.
{"title":"Polymer-modified DNA hydrogels for living mitochondria and nanozyme delivery in the treatment of rheumatoid arthritis","authors":"Fuxiao Wang , Yafei Han , Qirong Zhou , Shihao Sheng , Yan Hu , Hao Zhang , Xiao Chen , Chongru He , Hongbo Tan , Long Bai , Jiacan Su","doi":"10.1016/j.bioactmat.2024.12.027","DOIUrl":"10.1016/j.bioactmat.2024.12.027","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to joint deformities and functional impairments. Traditional treatment approaches, such as nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and molecular targeted therapies, often fail to simultaneously achieve efficient inflammation relief and cartilage tissue repair. DNA hydrogels, derived from nucleic acid nanotechnology, have demonstrated potential in RA therapy due to their programmability, high biocompatibility, and tunable degradation properties. However, their application is still hindered by challenges including high synthesis costs, immunogenicity risks, and uncontrolled degradation rates. To address these limitations, this study proposes a dual-action strategy involving a polymer-modified DNA hydrogel co-delivering nanozymes and living mitochondria to overcome the constraints of traditional therapies and comprehensively optimize RA treatment outcomes. The incorporation of functionalized polymers significantly reduces synthesis costs and immunogenicity while fine-tuning the degradation rate of the hydrogel, enabling sustained support during bone and cartilage repair. The hydrogel is loaded with Prussian blue nanozymes to scavenge excessive reactive oxygen species (ROS) within the RA microenvironment, alleviating inflammation, and facilitates intracellular delivery of living mitochondria to inhibit ROS production at its source, promoting tissue repair. By integrating endogenous ROS reduction with exogenous ROS clearance, this strategy markedly enhances therapeutic efficacy, offering a novel approach for precise RA treatment and advancing the clinical translation of biomaterials.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 448-459"},"PeriodicalIF":18.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395473","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}
Pub Date : 2025-02-12DOI: 10.1016/j.bioactmat.2025.02.005
Zichao Li , Leyang Zhang , Yang Wang , Yifu Zhu , Haomiao Shen , Juzheng Yuan , Xiao Li , Zhou Yu , Baoqiang Song
The homeostasis of the wound microenvironment is fundamental for scarless wound healing, while the excessive accumulation of transforming growth factor-beta (TGF-β) in the wound microenvironment always leads to hypertrophic scars (HS) formation by regulating cell fates and crosstalk among various types of cells, such as macrophages and fibroblasts. This study reports that an injectable, self-assembling LA-peptide hydrogel has the potential to facilitate scarless cutaneous wound healing through dynamically adsorbing TGF-β within the wound environment. We found that the released LA peptides led to the suppression of both the PI3K/Akt and TGF-β/Smad2/3 pathways in macrophages and fibroblasts. As expected, the application of LA-peptide hydrogel alleviated the M2 type polarization of macrophages and inhibited fibroblasts activation by adsorbing TGF-β both in vitro and in vivo. Furthermore, designated concentrations of the LA-peptide hydrogel achieved controlled release of LA peptides, enabling dynamic regulation of TGF-β for maintaining microenvironment homeostasis during different phases of wound healing. This contributed to the inhibition of HS formation without delaying wound healing in both a mouse full-thickness skin wound model and a rabbit ear scar model. Overall, the LA-peptide hydrogel provides promising avenues for promoting scarless healing of wounds, exemplifying precision medicine-guided targeting of specific pathogenic molecules, such as TGF-β, and highlighting the significance of dynamic regulation of TGF-β homeostasis in wound microenvironment.
{"title":"LA-peptide Hydrogel—Regulation of macrophage and fibroblast fates and their crosstalk via attenuating TGF-β to promote scarless wound healing","authors":"Zichao Li , Leyang Zhang , Yang Wang , Yifu Zhu , Haomiao Shen , Juzheng Yuan , Xiao Li , Zhou Yu , Baoqiang Song","doi":"10.1016/j.bioactmat.2025.02.005","DOIUrl":"10.1016/j.bioactmat.2025.02.005","url":null,"abstract":"<div><div>The homeostasis of the wound microenvironment is fundamental for scarless wound healing, while the excessive accumulation of transforming growth factor-beta (TGF-β) in the wound microenvironment always leads to hypertrophic scars (HS) formation by regulating cell fates and crosstalk among various types of cells, such as macrophages and fibroblasts. This study reports that an injectable, self-assembling LA-peptide hydrogel has the potential to facilitate scarless cutaneous wound healing through dynamically adsorbing TGF-β within the wound environment. We found that the released LA peptides led to the suppression of both the PI3K/Akt and TGF-β/Smad2/3 pathways in macrophages and fibroblasts. As expected, the application of LA-peptide hydrogel alleviated the M2 type polarization of macrophages and inhibited fibroblasts activation by adsorbing TGF-β both <em>in vitro</em> and <em>in vivo</em>. Furthermore, designated concentrations of the LA-peptide hydrogel achieved controlled release of LA peptides, enabling dynamic regulation of TGF-β for maintaining microenvironment homeostasis during different phases of wound healing. This contributed to the inhibition of HS formation without delaying wound healing in both a mouse full-thickness skin wound model and a rabbit ear scar model. Overall, the LA-peptide hydrogel provides promising avenues for promoting scarless healing of wounds, exemplifying precision medicine-guided targeting of specific pathogenic molecules, such as TGF-β, and highlighting the significance of dynamic regulation of TGF-β homeostasis in wound microenvironment.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 417-431"},"PeriodicalIF":18.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388137","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}
Pub Date : 2025-02-12DOI: 10.1016/j.bioactmat.2025.01.022
Jia Liu , Zuoyu Chen , Lixue Deng , Chundong Yao , Zhixin Zhou , Cheng Zhou , Yawen Bin , Miaodeng Liu , Liping Wang , Lin Wang , Zheng Wang
Hypoxia, a prevalent characteristic of solid tumors, substantially impairs the efficacy of cancer treatments. However, there are no feasible clinical approaches for treating hypoxic tumors. Here, we develop metal-phenolic networks (CuGI) utilizing the natural glycolysis inhibitor (epigallocatechin gallate) and the essential metal element in the human body (copper ions), specifically targeting and annihilating hypoxic cancer cells. CuGI redirects the metabolic pathway of hypoxic cancer cells from anaerobic glycolysis to oxidative phosphorylation, thereby enhancing reactive oxygen species production and promoting oligomerization of lipoylated proteins in the tricarboxylic acid cycle. Through targeted induction of oxidative and proteotoxic stresses, CuGI induces apoptosis and cuproptosis specifically in cancer cells under hypoxic conditions while sparing normal cells. Moreover, cancer cell membrane-coated CuGI (CuGI@CM) exhibits enhanced tumor penetration effect and demonstrates commendable biocompatibility, effectively suppressing colorectal tumor growth. Importantly, CuGI@CM, when combined with vascular disruptors or radiotherapy which aggravate tumor hypoxia, synergistically potentiates therapeutic efficacy. Thus, CuGI represents a specific and potent nanotherapeutic capable of selectively eliminating hypoxic tumors, offering promise in combination therapies to address tumor hypoxia.
{"title":"Metal-phenolic networks specifically eliminate hypoxic tumors by instigating oxidative and proteotoxic stresses","authors":"Jia Liu , Zuoyu Chen , Lixue Deng , Chundong Yao , Zhixin Zhou , Cheng Zhou , Yawen Bin , Miaodeng Liu , Liping Wang , Lin Wang , Zheng Wang","doi":"10.1016/j.bioactmat.2025.01.022","DOIUrl":"10.1016/j.bioactmat.2025.01.022","url":null,"abstract":"<div><div>Hypoxia, a prevalent characteristic of solid tumors, substantially impairs the efficacy of cancer treatments. However, there are no feasible clinical approaches for treating hypoxic tumors. Here, we develop metal-phenolic networks (CuGI) utilizing the natural glycolysis inhibitor (epigallocatechin gallate) and the essential metal element in the human body (copper ions), specifically targeting and annihilating hypoxic cancer cells. CuGI redirects the metabolic pathway of hypoxic cancer cells from anaerobic glycolysis to oxidative phosphorylation, thereby enhancing reactive oxygen species production and promoting oligomerization of lipoylated proteins in the tricarboxylic acid cycle. Through targeted induction of oxidative and proteotoxic stresses, CuGI induces apoptosis and cuproptosis specifically in cancer cells under hypoxic conditions while sparing normal cells. Moreover, cancer cell membrane-coated CuGI (CuGI@CM) exhibits enhanced tumor penetration effect and demonstrates commendable biocompatibility, effectively suppressing colorectal tumor growth. Importantly, CuGI@CM, when combined with vascular disruptors or radiotherapy which aggravate tumor hypoxia, synergistically potentiates therapeutic efficacy. Thus, CuGI represents a specific and potent nanotherapeutic capable of selectively eliminating hypoxic tumors, offering promise in combination therapies to address tumor hypoxia.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 361-377"},"PeriodicalIF":18.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388164","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}
Pub Date : 2025-02-12DOI: 10.1016/j.bioactmat.2025.01.032
Qiyu Zhan , Yulin Kuang , Xuyuan Chen , Yanzhen Yang , Linhui Jiang , Jian Chen , Lie Li , Junwei Wang , Shuoji Zhu , Huanlei Huang , Lei Wang , Ping Zhu , Ruiyuan Liu
Pyroptosis is an inflammatory form of programmed cell death with great potential in cancer immunotherapies. Photodynamic therapy (PDT) represents a promising treatment modality to trigger pyroptosis. However, the hypoxic microenvironment inside the tumors often induces limited therapeutic efficacy. Herein, in this work, the first type of mitochondrial-targeting oxime-ester photogenerator (T-Oximer) was constructed to boost type-I ROS/aryl free radicals which could induce DNA damage by DNA cleaving and facilitate high-efficiency pyroptosis-mediated photoimmunotherapy. Detailed mechanism investigations revealed that T-Oximer could produce aryl free radicals via photolysis reaction and generate type-I ROS (O2•− and •OH) based on the type-I electron transfer process. Meanwhile, T-Oximer could accumulate in the mitochondria, boost mitochondrial radicals, and damage mitochondria in hypoxic tumor cells. Of peculiar interest, T-Oixmer could bind with DNA and cleave DNA to induce DNA damage. Combined mitochondrial damage with DNA cleavage, T-Oximer can initiate pyroptosis, activate the ICD effect, and trigger robust systemic antitumor immunity for efficient tumor regression and metastasis suppression. Our finding provides a new strategy for constructing oxygen-independent photogenerator for high-efficiency pyroptosis-mediated anti-hypoxia photoimmunotherapy.
{"title":"Photo-generating Type-I ROS and aryl radicals by mitochondrial-targeting oxime-ester photogenerator for pyroptosis-mediated anti-hypoxia photoimmunotherapy","authors":"Qiyu Zhan , Yulin Kuang , Xuyuan Chen , Yanzhen Yang , Linhui Jiang , Jian Chen , Lie Li , Junwei Wang , Shuoji Zhu , Huanlei Huang , Lei Wang , Ping Zhu , Ruiyuan Liu","doi":"10.1016/j.bioactmat.2025.01.032","DOIUrl":"10.1016/j.bioactmat.2025.01.032","url":null,"abstract":"<div><div>Pyroptosis is an inflammatory form of programmed cell death with great potential in cancer immunotherapies. Photodynamic therapy (PDT) represents a promising treatment modality to trigger pyroptosis. However, the hypoxic microenvironment inside the tumors often induces limited therapeutic efficacy. Herein, in this work, the first type of mitochondrial-targeting oxime-ester photogenerator (T-Oximer) was constructed to boost type-I ROS/aryl free radicals which could induce DNA damage by DNA cleaving and facilitate high-efficiency pyroptosis-mediated photoimmunotherapy. Detailed mechanism investigations revealed that T-Oximer could produce aryl free radicals <em>via</em> photolysis reaction and generate type-I ROS (O<sub>2</sub><sup>•<strong>−</strong></sup> and •OH) based on the type-I electron transfer process. Meanwhile, T-Oximer could accumulate in the mitochondria, boost mitochondrial radicals, and damage mitochondria in hypoxic tumor cells. Of peculiar interest, T-Oixmer could bind with DNA and cleave DNA to induce DNA damage. Combined mitochondrial damage with DNA cleavage, T-Oximer can initiate pyroptosis, activate the ICD effect, and trigger robust systemic antitumor immunity for efficient tumor regression and metastasis suppression. Our finding provides a new strategy for constructing oxygen-independent photogenerator for high-efficiency pyroptosis-mediated anti-hypoxia photoimmunotherapy.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 327-342"},"PeriodicalIF":18.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388138","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}
Pub Date : 2025-02-12DOI: 10.1016/j.bioactmat.2025.01.039
Alexander A. Oliver , Cem Bilgin , Mitchell L. Connon , Andrew J. Vercnocke , Esref A. Bayraktar , Jonathan Cortese , Daying Dai , Yong Hong Ding , Sarah A. Erdahl , John Pederson , Kent D. Carlson , Adam J. Griebel , Jeremy E. Schaffer , Dan Dragomir-Daescu , Ramanathan Kadirvel , Roger J. Guillory II , David F. Kallmes
Flow diverting stents are braided, metallic endoluminal devices widely used to treat intracranial aneurysms. Bioresorbable flow diverters (BRFDs) are gaining traction as the next generation of flow diverter technology. BRFDs aim to occlude and heal the aneurysm before safely dissolving into the body, mitigating or eliminating complications associated with the permanent presence of conventional flow diverters such as thromboembolism and stenosis. Additional putative advantages of a BRFD include a reduction in metal induced medical imaging artifacts, a restoration of physiological vasoreactivity, and allowing physicians to re-access the aneurysm if an additional procedure is required. In this current study, iron-manganese-nitrogen (FeMnN) alloy BRFDs and permanent control FDs composed of an industry standard Cobalt-Nickel-Chromium alloy were deployed in the rabbit aorta. MicroCT and SEM corrosion analysis determined the FeMnN wire volumes and cross-sectional areas had reduced approximately 85 % and 95 % after 3- and 6-months implantation duration, respectively. Histological analysis demonstrated the BRFDs exhibited suitable biocompatibility, with no cases of in-stent thrombosis, clinically significant stenosis, or adverse tissue responses observed. Immunohistochemistry revealed the neointimas surrounding the BRFDs featured a confluent endothelium covering several layers of smooth muscle cells, with macrophages adjacent to the device wires. The macrophages were able to penetrate the corrosion product and were observed transporting corrosion products away from the implant site. This current work provides primary in vivo corrosion and biocompatibility data to the field for FeMn alloys, which we feel will stimulate and inform the design of next-generation bioresorbable endovascular devices.
{"title":"Evaluation of FeMnN alloy bioresorbable flow diverting stents in the rabbit abdominal aorta","authors":"Alexander A. Oliver , Cem Bilgin , Mitchell L. Connon , Andrew J. Vercnocke , Esref A. Bayraktar , Jonathan Cortese , Daying Dai , Yong Hong Ding , Sarah A. Erdahl , John Pederson , Kent D. Carlson , Adam J. Griebel , Jeremy E. Schaffer , Dan Dragomir-Daescu , Ramanathan Kadirvel , Roger J. Guillory II , David F. Kallmes","doi":"10.1016/j.bioactmat.2025.01.039","DOIUrl":"10.1016/j.bioactmat.2025.01.039","url":null,"abstract":"<div><div>Flow diverting stents are braided, metallic endoluminal devices widely used to treat intracranial aneurysms. Bioresorbable flow diverters (BRFDs) are gaining traction as the next generation of flow diverter technology. BRFDs aim to occlude and heal the aneurysm before safely dissolving into the body, mitigating or eliminating complications associated with the permanent presence of conventional flow diverters such as thromboembolism and stenosis. Additional putative advantages of a BRFD include a reduction in metal induced medical imaging artifacts, a restoration of physiological vasoreactivity, and allowing physicians to re-access the aneurysm if an additional procedure is required. In this current study, iron-manganese-nitrogen (FeMnN) alloy BRFDs and permanent control FDs composed of an industry standard Cobalt-Nickel-Chromium alloy were deployed in the rabbit aorta. MicroCT and SEM corrosion analysis determined the FeMnN wire volumes and cross-sectional areas had reduced approximately 85 % and 95 % after 3- and 6-months implantation duration, respectively. Histological analysis demonstrated the BRFDs exhibited suitable biocompatibility, with no cases of in-stent thrombosis, clinically significant stenosis, or adverse tissue responses observed. Immunohistochemistry revealed the neointimas surrounding the BRFDs featured a confluent endothelium covering several layers of smooth muscle cells, with macrophages adjacent to the device wires. The macrophages were able to penetrate the corrosion product and were observed transporting corrosion products away from the implant site. This current work provides primary <em>in vivo</em> corrosion and biocompatibility data to the field for FeMn alloys, which we feel will stimulate and inform the design of next-generation bioresorbable endovascular devices.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 18-28"},"PeriodicalIF":18.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394768","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}
Pub Date : 2025-02-12DOI: 10.1016/j.bioactmat.2025.02.002
Kexin Li , En Xie , Chengyuan Liu , Jie Hu , Qianglong Chen , Jiaying Li , Huan Wang , Qingchen Meng , Dachuan Liu , Bin Meng , Ting Liang , Jinjin Ma , Zhangqin Yuan , Lijie Wang , Wenmiao Shu , Haijiao Mao , Fengxuan Han , Bin Li
Addressing the challenge of eliminating bacteria and stimulating osteogenesis in infectious bone defects, where cells and bacteria coexist within the microenvironment, presents a significant hurdle. In this study, a strategy of targeting bacteria is proposed to address this challenge. For this purpose, a methacrylated gelatin composite hydrogel containing zinc ion and D-type cysteine-modified polydopamine nanoparticles (PZC) is developed. The D-cysteine, involved in the metabolism of the bacterial peptidoglycan chain, allows PZC to specifically target bacteria, exhibiting a form of “disguise strategy”. Through the targeting effect, this composite hydrogel can selectively kill bacteria and promote osteogenesis combing photothermal therapy with Zn2+ release, which showcases spatial controllability. Moreover, the antibacterial ability will be further improved after Near-infrared light irradiation. The multifunctional hydrogel containing Zn2+ modified nanoparticles can also promote osteogenic differentiation of bone marrow stem cells. Animal studies have revealed that the multifunctional hydrogel can inhibit bacteria growth and promote repair of infectious bone defects in rats. Findings from this study imply that endowing the nanoparticles with bacteria-targeting function can precisely control the events in cells and bacteria in the complex microenvironment, which can provide insights for the treatment of complex diseases with antibacterial requirements.
{"title":"“Disguise strategy” to bacteria: A multifunctional hydrogel with bacteria-targeting and photothermal conversion properties for the repair of infectious bone defects","authors":"Kexin Li , En Xie , Chengyuan Liu , Jie Hu , Qianglong Chen , Jiaying Li , Huan Wang , Qingchen Meng , Dachuan Liu , Bin Meng , Ting Liang , Jinjin Ma , Zhangqin Yuan , Lijie Wang , Wenmiao Shu , Haijiao Mao , Fengxuan Han , Bin Li","doi":"10.1016/j.bioactmat.2025.02.002","DOIUrl":"10.1016/j.bioactmat.2025.02.002","url":null,"abstract":"<div><div>Addressing the challenge of eliminating bacteria and stimulating osteogenesis in infectious bone defects, where cells and bacteria coexist within the microenvironment, presents a significant hurdle. In this study, a strategy of targeting bacteria is proposed to address this challenge. For this purpose, a methacrylated gelatin composite hydrogel containing zinc ion and D-type cysteine-modified polydopamine nanoparticles (PZC) is developed. The D-cysteine, involved in the metabolism of the bacterial peptidoglycan chain, allows PZC to specifically target bacteria, exhibiting a form of “disguise strategy”. Through the targeting effect, this composite hydrogel can selectively kill bacteria and promote osteogenesis combing photothermal therapy with Zn<sup>2+</sup> release, which showcases spatial controllability. Moreover, the antibacterial ability will be further improved after Near-infrared light irradiation. The multifunctional hydrogel containing Zn<sup>2+</sup> modified nanoparticles can also promote osteogenic differentiation of bone marrow stem cells. Animal studies have revealed that the multifunctional hydrogel can inhibit bacteria growth and promote repair of infectious bone defects in rats. Findings from this study imply that endowing the nanoparticles with bacteria-targeting function can precisely control the events in cells and bacteria in the complex microenvironment, which can provide insights for the treatment of complex diseases with antibacterial requirements.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"47 ","pages":"Pages 343-360"},"PeriodicalIF":18.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388163","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}
Pub Date : 2025-02-12DOI: 10.1016/j.bioactmat.2025.02.014
Chengli Yang , Xukun Liao , Kai Zhou , Yongchao Yao , Xinlong He , Wen Zhong , Dan Zheng , Yan Yang , Ming Li , Meng Zhou , Yadi Zhou , Lin Li , Yang Bai , Kun Shi , Zhiyong Qian
Breast cancer is the most prevalent and lethal malignancy among females, with a critical need for safer and less invasive treatments. Photodynamic therapy (PDT) can effectively eliminate tumor cells with minimal side effects. Furthermore, the combination of PDT and immunotherapy using nanoparticles has shown promise in treating both primary and distant metastatic tumor cells. Therefore, this study proposes applying the PDT-immunotherapy combination to breast cancer treatment. However, the low immunogenicity characteristic of “cold” tumors in part of breast cancer significantly diminishes therapeutic efficacy. To address this challenge, here, a nano-gel system (designated as HCSC-gel) is constructed, which co-delivers a mitochondria-targeted photosensitizer and a STING agonist, capable of robustly activating “cold” tumor immunity. This system is further enhanced by collagenase (CN) to improve therapeutic outcomes. Upon injection into the primary tumor site, HCSC-gel rapidly forms a gel matrix, releasing CN to degrade the tumor extracellular matrix and facilitate the penetration of photosensitizers, STING agonists, and oxygen into the tumor tissue. Under laser irradiation, PDT and STING-mediated immune responses are activated, reversing the low immunogenicity of breast cancer and effectively treating both primary and metastatic lesions. This HCSC-gel nano hydrogel delivery platform is anticipated to provide novel insights for the clinical management of breast cancer and other low immunogenic “cold” tumors, offering significant benefits to patients.
{"title":"Multifunctional nanoparticles and collagenase dual loaded thermosensitive hydrogel system for enhanced tumor-penetration, reversed immune suppression and photodynamic-immunotherapy","authors":"Chengli Yang , Xukun Liao , Kai Zhou , Yongchao Yao , Xinlong He , Wen Zhong , Dan Zheng , Yan Yang , Ming Li , Meng Zhou , Yadi Zhou , Lin Li , Yang Bai , Kun Shi , Zhiyong Qian","doi":"10.1016/j.bioactmat.2025.02.014","DOIUrl":"10.1016/j.bioactmat.2025.02.014","url":null,"abstract":"<div><div>Breast cancer is the most prevalent and lethal malignancy among females, with a critical need for safer and less invasive treatments. Photodynamic therapy (PDT) can effectively eliminate tumor cells with minimal side effects. Furthermore, the combination of PDT and immunotherapy using nanoparticles has shown promise in treating both primary and distant metastatic tumor cells. Therefore, this study proposes applying the PDT-immunotherapy combination to breast cancer treatment. However, the low immunogenicity characteristic of “cold” tumors in part of breast cancer significantly diminishes therapeutic efficacy. To address this challenge, here, a nano-gel system (designated as HCSC-gel) is constructed, which co-delivers a mitochondria-targeted photosensitizer and a STING agonist, capable of robustly activating “cold” tumor immunity. This system is further enhanced by collagenase (CN) to improve therapeutic outcomes. Upon injection into the primary tumor site, HCSC-gel rapidly forms a gel matrix, releasing CN to degrade the tumor extracellular matrix and facilitate the penetration of photosensitizers, STING agonists, and oxygen into the tumor tissue. Under laser irradiation, PDT and STING-mediated immune responses are activated, reversing the low immunogenicity of breast cancer and effectively treating both primary and metastatic lesions. This HCSC-gel nano hydrogel delivery platform is anticipated to provide novel insights for the clinical management of breast cancer and other low immunogenic “cold” tumors, offering significant benefits to patients.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 1-17"},"PeriodicalIF":18.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387336","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}
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