Pub Date : 2025-04-16DOI: 10.1016/j.biomaterials.2025.123348
Yunyi Liu , Quanle Cao , Shengyi Yong , Jing Wang , Xuening Chen , Yumei Xiao , Jiangli Lin , Mingli Yang , Kefeng Wang , Xiangfeng Li , Xiangdong Zhu , Xingdong Zhang
Osteoinduction is an important feature of the next generation of bone repair materials. But the key structural factors and parameters of osteoinductive scaffolds are not yet clarified. This study leverages the efficiency of high-throughput screening in identifying key structural factors, performs screening of 24 different porous structures using 3D printed calcium phosphate (CaP) ceramic scaffolds. Based on in vitro and in vivo evaluations, along with machine learning and nonlinear fitting, it explores the complex relationship between osteoinductive properties and scaffold configurations. Results indicate that bone regenerative ability is largely affected by porosity and specific surface area (SSA), while pore geometry has a negligible effect. The optimal structural parameters were identified as a porous structure with SSA of 10.49–10.69 mm2 mm−3 and permeability of 3.74 × 10−9 m2, which enhances osteoinductivity and scaffold properties, corresponding to approximately 65 %–70 % porosity. Moreover, nonlinear fitting reveals specific correlations among SSA, permeability and osteogenic gene expressions. We established a data-driven high-throughput screening methodology and proposed a parametric benchmark for osteoinductive structures, providing critical insights for the design of future osteoinductive scaffolds.
{"title":"Optimal structural characteristics of osteoinductivity in bioceramics derived from a novel high-throughput screening plus machine learning approach","authors":"Yunyi Liu , Quanle Cao , Shengyi Yong , Jing Wang , Xuening Chen , Yumei Xiao , Jiangli Lin , Mingli Yang , Kefeng Wang , Xiangfeng Li , Xiangdong Zhu , Xingdong Zhang","doi":"10.1016/j.biomaterials.2025.123348","DOIUrl":"10.1016/j.biomaterials.2025.123348","url":null,"abstract":"<div><div>Osteoinduction is an important feature of the next generation of bone repair materials. But the key structural factors and parameters of osteoinductive scaffolds are not yet clarified. This study leverages the efficiency of high-throughput screening in identifying key structural factors, performs screening of 24 different porous structures using 3D printed calcium phosphate (CaP) ceramic scaffolds. Based on <em>in vitro</em> and <em>in vivo</em> evaluations, along with machine learning and nonlinear fitting, it explores the complex relationship between osteoinductive properties and scaffold configurations. Results indicate that bone regenerative ability is largely affected by porosity and specific surface area (SSA), while pore geometry has a negligible effect. The optimal structural parameters were identified as a porous structure with SSA of 10.49–10.69 mm<sup>2</sup> mm<sup>−3</sup> and permeability of 3.74 × 10<sup>−9</sup> m<sup>2</sup>, which enhances osteoinductivity and scaffold properties, corresponding to approximately 65 %–70 % porosity. Moreover, nonlinear fitting reveals specific correlations among SSA, permeability and osteogenic gene expressions. We established a data-driven high-throughput screening methodology and proposed a parametric benchmark for osteoinductive structures, providing critical insights for the design of future osteoinductive scaffolds.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123348"},"PeriodicalIF":12.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-16DOI: 10.1016/j.biomaterials.2025.123350
Nana Meng , Jiasheng Lu , Jianfen Zhou , Shengmin Yang , Chen Zhang , Ruiyi Jia , Yuan Ding , Yanning Bao , Jun Wang , Xiaopei Ma , Ruohan Chen , Zhixuan Jiang , Cao Xie , Linwei Lu , Weiyue Lu
One of the challenges for the clinical translation of active targeting nanomedicines is the adverse interactions between targeting ligands and blood components. Herein, a novel regularity, which reveals the interactions between cyclic RGD (Arg-Gly-Asp) peptide-modified liposomes and complement components in blood, is reported. As the nucleophilicity of arginine guanidine group within the cyclic RGD-like peptide increases, targeting liposomes potentiate complement cascade via the amplification loop of complement 3 (C3), ultimately leading to accelerated blood clearance, increased deposition in the reticuloendothelial system (RES) organs, enhanced immune responses, and potential side effects. By appropriately reducing the nucleophilicity of guanidine group, cyclic R2 peptide is designed for modification of liposomes to target integrin αvβ3. Compared to the widely used targeting molecule c(RGDyK), R2 eliminates the negative effects of C3 opsonization and specific antibody production, significantly improves the in vivo immunocompatibility of targeting liposomes, and demonstrates superior anti-tumor efficacy in mouse models of orthotopic breast cancer and glioma. Thus, the proposed regularity of interactions between guanidine nucleophilicity and C3, along with the successful application of the low complement activation capacity targeting ligand R2, provides new insights for addressing challenges related to complement activation in the clinical translation of active targeting nanomedicines.
{"title":"Improved immunocompatibility of active targeting liposomes by attenuating nucleophilic attack of cyclic RGD peptides on complement 3","authors":"Nana Meng , Jiasheng Lu , Jianfen Zhou , Shengmin Yang , Chen Zhang , Ruiyi Jia , Yuan Ding , Yanning Bao , Jun Wang , Xiaopei Ma , Ruohan Chen , Zhixuan Jiang , Cao Xie , Linwei Lu , Weiyue Lu","doi":"10.1016/j.biomaterials.2025.123350","DOIUrl":"10.1016/j.biomaterials.2025.123350","url":null,"abstract":"<div><div>One of the challenges for the clinical translation of active targeting nanomedicines is the adverse interactions between targeting ligands and blood components. Herein, a novel regularity, which reveals the interactions between cyclic RGD (Arg-Gly-Asp) peptide-modified liposomes and complement components in blood, is reported. As the nucleophilicity of arginine guanidine group within the cyclic RGD-like peptide increases, targeting liposomes potentiate complement cascade via the amplification loop of complement 3 (C3), ultimately leading to accelerated blood clearance, increased deposition in the reticuloendothelial system (RES) organs, enhanced immune responses, and potential side effects. By appropriately reducing the nucleophilicity of guanidine group, cyclic R2 peptide is designed for modification of liposomes to target integrin <em>α</em><sub><em>v</em></sub><em>β</em><sub><em>3</em></sub>. Compared to the widely used targeting molecule c(RGDyK), R2 eliminates the negative effects of C3 opsonization and specific antibody production, significantly improves the <em>in vivo</em> immunocompatibility of targeting liposomes, and demonstrates superior anti-tumor efficacy in mouse models of orthotopic breast cancer and glioma. Thus, the proposed regularity of interactions between guanidine nucleophilicity and C3, along with the successful application of the low complement activation capacity targeting ligand R2, provides new insights for addressing challenges related to complement activation in the clinical translation of active targeting nanomedicines.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123350"},"PeriodicalIF":12.8,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-15DOI: 10.1016/j.biomaterials.2025.123344
Zhihao Chen , Yi Tai , Chuangzhong Deng , Yameng Sun , Hongmin Chen , Tianqi Luo , Jiaming Lin , Weiqing Chen , Huaiyuan Xu , Guohui Song , Qinglian Tang , Jinchang Lu , Xiaojun Zhu , Shijun Wen , Jin Wang
Sarcomas are highly malignant tumors characterized by their heterogeneity and resistance to conventional therapies, which significantly limit treatment options. EZH2 is highly expressed in sarcomas, but targeting it is difficult. In this study, we uncovered the non-canonical transcriptional mechanisms of EZH2 in sarcoma and highlighted the essential role of EZH2 in regulating YAP1 through non-canonical transcriptional pathways in the progression of sarcoma. Building on this, we developed YM@VBM, a novel and versatile nano-PROTAC (proteolysis-targeting chimera), by integrating a polyphenol-vanadium oxide system with the EZH2 degrader YM281 PROTAC, encapsulated in methoxy polyethylene glycol-NH2 to enhance biocompatibility. To further facilitate targeted drug delivery to tumors, YM@VBM nano-PROTACs were incorporated into microneedle patches. Our engineered YM@VBM exhibited multiple functionalities, including the peroxidase-like activity to generate reactive oxygen species, depletion of glutathione, and photothermal effects, specifically targeting sarcoma characteristics. YM@VBM significantly enhanced targeting efficacy via inducing potent EZH2 degradation. Most importantly, it can also activate anti-tumor immunity via excluding myeloid-derived suppressor cells, maturing dendritic cells, and forming tertiary lymphoid structures. Hence, we reveal that YM@VBM presents a promising treatment strategy for sarcoma, offering a multifaceted approach to combat this challenging malignancy.
{"title":"Innovative sarcoma therapy using multifaceted nano-PROTAC-induced EZH2 degradation and immunity enhancement","authors":"Zhihao Chen , Yi Tai , Chuangzhong Deng , Yameng Sun , Hongmin Chen , Tianqi Luo , Jiaming Lin , Weiqing Chen , Huaiyuan Xu , Guohui Song , Qinglian Tang , Jinchang Lu , Xiaojun Zhu , Shijun Wen , Jin Wang","doi":"10.1016/j.biomaterials.2025.123344","DOIUrl":"10.1016/j.biomaterials.2025.123344","url":null,"abstract":"<div><div>Sarcomas are highly malignant tumors characterized by their heterogeneity and resistance to conventional therapies, which significantly limit treatment options. EZH2 is highly expressed in sarcomas, but targeting it is difficult. In this study, we uncovered the non-canonical transcriptional mechanisms of EZH2 in sarcoma and highlighted the essential role of EZH2 in regulating YAP1 through non-canonical transcriptional pathways in the progression of sarcoma. Building on this, we developed YM@VBM, a novel and versatile nano-PROTAC (proteolysis-targeting chimera), by integrating a polyphenol-vanadium oxide system with the EZH2 degrader YM281 PROTAC, encapsulated in methoxy polyethylene glycol-NH<sub>2</sub> to enhance biocompatibility. To further facilitate targeted drug delivery to tumors, YM@VBM nano-PROTACs were incorporated into microneedle patches. Our engineered YM@VBM exhibited multiple functionalities, including the peroxidase-like activity to generate reactive oxygen species, depletion of glutathione, and photothermal effects, specifically targeting sarcoma characteristics. YM@VBM significantly enhanced targeting efficacy via inducing potent EZH2 degradation. Most importantly, it can also activate anti-tumor immunity via excluding myeloid-derived suppressor cells, maturing dendritic cells, and forming tertiary lymphoid structures. Hence, we reveal that YM@VBM presents a promising treatment strategy for sarcoma, offering a multifaceted approach to combat this challenging malignancy.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123344"},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-15DOI: 10.1016/j.biomaterials.2025.123343
Kai Chen , Shan Gao , Xuenan Gu , Li Zhao , Yunan Lu , Jinwu Bai , Linjun Huang , Hongtao Yang , Yu Qin , Fang Zhou , Yongcan Huang , Yang Lv , Yufeng Zheng
Implants with strong osteogenic properties are crucial for effective bone repair in clinical settings. Recently, biodegradable zinc (Zn)-based metals have shown significant potential as orthopedic implants. However, pure Zn is prone to pitting corrosion and exhibits insufficient osteogenic activity in vivo. To enhance the degradation behavior and osteogenic potential of Zn-based implants, this study developed metal-semimetal Zn–Ge alloys with varying Ge content. The addition of Ge significantly promotes the formation of eutectic Ge phases, refines the microstructure, and improves the mechanical properties of the implants. Incorporating ∼3 wt% Ge into the matrix also facilitates enhanced Zn2+ release and ensures uniform biodegradation. Besides, the formation of uniformly distributed heteroid Zn–Ge microgalvanic cells provides a balance between osteogenic and bacteriostatic effects. In vivo tests using a femoral condyle defect model demonstrate that Zn–3Ge implants have favorable osteogenic property and excellent biosafety; the enhanced osteogenic activity of the alloy is attributed to intracellular Zn2+ activation of the Wnt signaling pathway, which promotes osteoblast differentiation, cell proliferation, survival, as well as extracellular matrix mineralization and osteogenesis. The incorporation of eutectic Ge phases and effective creation of microgalvanic cells offer a promising strategy for optimizing the biological function of Zn-based implants.
{"title":"A metal-semimetal Zn–Ge alloy with modified biodegradation behavior and enhanced osteogenic activity mediated by eutectic Ge phases-induced microgalvanic cells","authors":"Kai Chen , Shan Gao , Xuenan Gu , Li Zhao , Yunan Lu , Jinwu Bai , Linjun Huang , Hongtao Yang , Yu Qin , Fang Zhou , Yongcan Huang , Yang Lv , Yufeng Zheng","doi":"10.1016/j.biomaterials.2025.123343","DOIUrl":"10.1016/j.biomaterials.2025.123343","url":null,"abstract":"<div><div>Implants with strong osteogenic properties are crucial for effective bone repair in clinical settings. Recently, biodegradable zinc (Zn)-based metals have shown significant potential as orthopedic implants. However, pure Zn is prone to pitting corrosion and exhibits insufficient osteogenic activity in vivo. To enhance the degradation behavior and osteogenic potential of Zn-based implants, this study developed metal-semimetal Zn–Ge alloys with varying Ge content. The addition of Ge significantly promotes the formation of eutectic Ge phases, refines the microstructure, and improves the mechanical properties of the implants. Incorporating ∼3 wt% Ge into the matrix also facilitates enhanced Zn<sup>2+</sup> release and ensures uniform biodegradation. Besides, the formation of uniformly distributed heteroid Zn–Ge microgalvanic cells provides a balance between osteogenic and bacteriostatic effects. In vivo tests using a femoral condyle defect model demonstrate that Zn–3Ge implants have favorable osteogenic property and excellent biosafety; the enhanced osteogenic activity of the alloy is attributed to intracellular Zn<sup>2+</sup> activation of the Wnt signaling pathway, which promotes osteoblast differentiation, cell proliferation, survival, as well as extracellular matrix mineralization and osteogenesis. The incorporation of eutectic Ge phases and effective creation of microgalvanic cells offer a promising strategy for optimizing the biological function of Zn-based implants.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123343"},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-15DOI: 10.1016/j.biomaterials.2025.123345
Limin Zhai , Yifei Gao , Hao Yang , Haoyuan Wang , Beining Liao , Yuxue Cheng , Chao Liu , Jingfeng Che , Kunwen Xia , Lingkun Zhang , Yanqing Guan
Parkinson's disease (PD) is characterized by the pathological aggregation of α-synuclein (α-syn) and neuroinflammation. Current gene therapies face challenges in nuclear delivery and resolving pre-existing α-syn aggregates. Here, we developed glucose-and trehalose-functionalized carbonized polymer dots (GT-PCDs) loaded with plasmid DNA (pDNA) for targeted gene delivery and autophagy restoration. The GT-PCDs@pDNA nanoparticles exhibit reactive oxygen species (ROS)-responsive behavior, enabling efficient nuclear entry under oxidative stress conditions. Both in vitro and in vivo studies demonstrated that GT-PCDs@pDNA effectively silenced SNCA gene expression, reduced α-syn aggregates, and restored autophagic flux by promoting transcription factor EB (TFEB) nuclear translocation. Moreover, GT-PCDs@pDNA enhanced blood-brain barrier (BBB) permeability via glucose transporter 1 (Glut-1)-mediated transcytosis, significantly improving motor deficits and reducing neuroinflammation in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. This multifunctional nanocarrier system offers a promising strategy for combined gene therapy and autophagy modulation in neurodegenerative diseases.
{"title":"A ROS-Responsive nanoparticle for nuclear gene delivery and autophagy restoration in Parkinson's disease therapy","authors":"Limin Zhai , Yifei Gao , Hao Yang , Haoyuan Wang , Beining Liao , Yuxue Cheng , Chao Liu , Jingfeng Che , Kunwen Xia , Lingkun Zhang , Yanqing Guan","doi":"10.1016/j.biomaterials.2025.123345","DOIUrl":"10.1016/j.biomaterials.2025.123345","url":null,"abstract":"<div><div>Parkinson's disease (PD) is characterized by the pathological aggregation of α-synuclein (α-syn) and neuroinflammation. Current gene therapies face challenges in nuclear delivery and resolving pre-existing α-syn aggregates. Here, we developed glucose-and trehalose-functionalized carbonized polymer dots (GT-PCDs) loaded with plasmid DNA (pDNA) for targeted gene delivery and autophagy restoration. The GT-PCDs@pDNA nanoparticles exhibit reactive oxygen species (ROS)-responsive behavior, enabling efficient nuclear entry under oxidative stress conditions. Both in vitro and in vivo studies demonstrated that GT-PCDs@pDNA effectively silenced <em>SNCA</em> gene expression, reduced α-syn aggregates, and restored autophagic flux by promoting transcription factor EB (TFEB) nuclear translocation. Moreover, GT-PCDs@pDNA enhanced blood-brain barrier (BBB) permeability via glucose transporter 1 (Glut-1)-mediated transcytosis, significantly improving motor deficits and reducing neuroinflammation in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. This multifunctional nanocarrier system offers a promising strategy for combined gene therapy and autophagy modulation in neurodegenerative diseases.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123345"},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-15DOI: 10.1016/j.biomaterials.2025.123342
Ruyan Xie , Duoyang Fan , Xiang Cheng , Ying Yin , Haohan Li , Seraphine V. Wegner , Fei Chen , Wenbin Zeng
Bacteria-based therapy has emerged as a promising strategy for cancer treatment, offering the potential for targeted tumor delivery, immune activation, and modulation of the tumor microenvironment. However, the unpredictable behavior, safety concerns, and limited efficacy of wild-type bacteria pose significant challenges to their clinical translation. Recent advancements in synthetic biology and chemical engineering have enabled the development of precisely engineered bacterial platforms with enhanced controllability, targeted delivery, and reduced toxicity. This review summarize the current progress of engineered bacteria in cancer therapy. We first introduce the theoretical underpinnings and key advantages of bacterial therapies in cancer. Subsequently, we delve into the applications of genetic engineering and chemical modification techniques to enhance their therapeutic potential. Finally, we address critical challenges and future prospects, with a focus on improving safety and efficacy. This review aims to stimulate further research and provide valuable insights into the development of engineered bacterial therapies for precision oncology.
{"title":"Living therapeutics: Precision diagnosis and therapy with engineered bacteria","authors":"Ruyan Xie , Duoyang Fan , Xiang Cheng , Ying Yin , Haohan Li , Seraphine V. Wegner , Fei Chen , Wenbin Zeng","doi":"10.1016/j.biomaterials.2025.123342","DOIUrl":"10.1016/j.biomaterials.2025.123342","url":null,"abstract":"<div><div>Bacteria-based therapy has emerged as a promising strategy for cancer treatment, offering the potential for targeted tumor delivery, immune activation, and modulation of the tumor microenvironment. However, the unpredictable behavior, safety concerns, and limited efficacy of wild-type bacteria pose significant challenges to their clinical translation. Recent advancements in synthetic biology and chemical engineering have enabled the development of precisely engineered bacterial platforms with enhanced controllability, targeted delivery, and reduced toxicity. This review summarize the current progress of engineered bacteria in cancer therapy. We first introduce the theoretical underpinnings and key advantages of bacterial therapies in cancer. Subsequently, we delve into the applications of genetic engineering and chemical modification techniques to enhance their therapeutic potential. Finally, we address critical challenges and future prospects, with a focus on improving safety and efficacy. This review aims to stimulate further research and provide valuable insights into the development of engineered bacterial therapies for precision oncology.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123342"},"PeriodicalIF":12.8,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-14DOI: 10.1016/j.biomaterials.2025.123346
Ya-Xing Li , Long-Mei Zhao , Xiu-Zhen Zhang , Xi-Kun Ma , Jing-Qi Liang , Ting-Jiang Gan , Heng Gong , Yan-Lin Jiang , Ye Wu , Yu-Ting Song , Yi Zhang , Yue Li , Xiao-Ting Chen , Cong-Hui Xu , Xiang-Yu Ouyang , Jesse Li-Ling , Hui Zhang , Hui-Qi Xie
Challenges still exist to develop an ideal cell-free nerve guidance conduit (NGC) providing a favorable microenvironment for rapid and successful nerve regeneration. Proteomic analysis revealed that extracellular matrix (ECM) derived from smooth muscle cells (SMCs) was abundant in nerve-related active proteins and significantly enriched signaling pathways involved in nerve regeneration. However, whether NGCs based on SMCs-derived ECM modification strategy promote nerve regeneration remains unclear. In the study, we investigated the neuroregenerative effect of SMCs-derived ECM and developed a novel NGC (MyoNerve) by coating small intestinal submucosa (SIS) with SMCs-derived ECM. The SMCs-ECM was rich in neurotrophic factors, which endowed MyoNerve with remarkable neuroregenerative capabilities by promoting the expression of genes implicated in aspects of neuronal maintenance and activating signaling pathways involved in nerve regeneration. In vitro, MyoNerve exhibited excellent bioactivity for accelerating angiogenesis, regulating macrophages polarization, promoting the proliferation, migration and elongation of Schwann cells, enhancing differentiation of PC12 cells, and inducing the neurite outgrowth of dorsal root ganglia. In the model of rat sciatic nerve 10 mm defect, MyoNerve showed great potential for functional nerve regeneration by promoting angiogenesis, proliferation and migration of Schwann cells and neuron, axonal regeneration, remyelination, and neurological functional recovery.
{"title":"Smooth muscle extracellular matrix modified small intestinal submucosa conduits promote peripheral nerve repair","authors":"Ya-Xing Li , Long-Mei Zhao , Xiu-Zhen Zhang , Xi-Kun Ma , Jing-Qi Liang , Ting-Jiang Gan , Heng Gong , Yan-Lin Jiang , Ye Wu , Yu-Ting Song , Yi Zhang , Yue Li , Xiao-Ting Chen , Cong-Hui Xu , Xiang-Yu Ouyang , Jesse Li-Ling , Hui Zhang , Hui-Qi Xie","doi":"10.1016/j.biomaterials.2025.123346","DOIUrl":"10.1016/j.biomaterials.2025.123346","url":null,"abstract":"<div><div>Challenges still exist to develop an ideal cell-free nerve guidance conduit (NGC) providing a favorable microenvironment for rapid and successful nerve regeneration. Proteomic analysis revealed that extracellular matrix (ECM) derived from smooth muscle cells (SMCs) was abundant in nerve-related active proteins and significantly enriched signaling pathways involved in nerve regeneration. However, whether NGCs based on SMCs-derived ECM modification strategy promote nerve regeneration remains unclear. In the study, we investigated the neuroregenerative effect of SMCs-derived ECM and developed a novel NGC (MyoNerve) by coating small intestinal submucosa (SIS) with SMCs-derived ECM. The SMCs-ECM was rich in neurotrophic factors, which endowed MyoNerve with remarkable neuroregenerative capabilities by promoting the expression of genes implicated in aspects of neuronal maintenance and activating signaling pathways involved in nerve regeneration. <em>In vitro</em>, MyoNerve exhibited excellent bioactivity for accelerating angiogenesis, regulating macrophages polarization, promoting the proliferation, migration and elongation of Schwann cells, enhancing differentiation of PC12 cells, and inducing the neurite outgrowth of dorsal root ganglia. In the model of rat sciatic nerve 10 mm defect, MyoNerve showed great potential for functional nerve regeneration by promoting angiogenesis, proliferation and migration of Schwann cells and neuron, axonal regeneration, remyelination, and neurological functional recovery.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123346"},"PeriodicalIF":12.8,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-12DOI: 10.1016/j.biomaterials.2025.123331
Jae Min Jung , Min Sang Lee , Young Kyu Seo , Jung Eun Lee , Su Yeon Lim , Dahwun Kim , Siyan Lyu , Chaeeun Park , Byung Deok Kim , Ju Hwa Shin , Ji Hyun Lee , Pin Liu , Junku Jung , João Conde , Thavasyappan Thambi , Ji Hoon Jeong , Doo Sung Lee
Recent outbreaks and the global spread of infectious diseases increased the need for the development of mucosal vaccines because of their ability to induce both an antigen-specific humoral and cellular immune response. Vaccines are commonly administered via a systemic route which is ineffective at inducing mucosal immunity. Therefore, developing mucosal vaccines is necessary to prevent and treat diseases that could not only elicit mucosal immune responses but also facilitate mass vaccination via a needle-free approach. Despite the benefits of mucosal vaccines, inducing mucosal immunity remains difficult due to the low antigen stability at mucosal sites. Herein, we developed a co-delivery platform using a polymeric nanoparticle carrier to upregulate the immune responses by improving the antigen's stability. Through hydrophobic and ionic interactions, the cationic polymeric nanoparticle composed of secondary bile acid conjugated polyethyleneimine (DA3) can load both TLR7/8 agonist resiquimod (R848) and anionic ovalbumin (OVA) antigen. The DA3/R848/OVA nanovaccine based co-delivery system can boost immune responses through binding affinity with dendritic cells (DCs). The results showed that DA3/R848/OVA could activate DCs better than OVA or OVA + R848. Furthermore, the nanovaccine demonstrated a strong therapeutic effect by significantly suppressing tumor growth in a B16-OVA melanoma model. Additionally, prophylactic immunization with the nanovaccine effectively induced immunological memory, leading to sustained tumor suppression upon challenge. Intranasal delivery of DA3/R848/OVA upregulates the antitumor effect in the metastatic lung tumor foci and the survival rates. These results suggest that intranasal immunization using the DA3/R848/OVA nanovaccine can promote needle-free vaccination.
{"title":"Bioengineered metastatic cancer nanovaccine with a TLR7/8 agonist for needle-free intranasal immunization","authors":"Jae Min Jung , Min Sang Lee , Young Kyu Seo , Jung Eun Lee , Su Yeon Lim , Dahwun Kim , Siyan Lyu , Chaeeun Park , Byung Deok Kim , Ju Hwa Shin , Ji Hyun Lee , Pin Liu , Junku Jung , João Conde , Thavasyappan Thambi , Ji Hoon Jeong , Doo Sung Lee","doi":"10.1016/j.biomaterials.2025.123331","DOIUrl":"10.1016/j.biomaterials.2025.123331","url":null,"abstract":"<div><div>Recent outbreaks and the global spread of infectious diseases increased the need for the development of mucosal vaccines because of their ability to induce both an antigen-specific humoral and cellular immune response. Vaccines are commonly administered via a systemic route which is ineffective at inducing mucosal immunity. Therefore, developing mucosal vaccines is necessary to prevent and treat diseases that could not only elicit mucosal immune responses but also facilitate mass vaccination via a needle-free approach. Despite the benefits of mucosal vaccines, inducing mucosal immunity remains difficult due to the low antigen stability at mucosal sites. Herein, we developed a co-delivery platform using a polymeric nanoparticle carrier to upregulate the immune responses by improving the antigen's stability. Through hydrophobic and ionic interactions, the cationic polymeric nanoparticle composed of secondary bile acid conjugated polyethyleneimine (DA3) can load both TLR7/8 agonist resiquimod (R848) and anionic ovalbumin (OVA) antigen. The DA3/R848/OVA nanovaccine based co-delivery system can boost immune responses through binding affinity with dendritic cells (DCs). The results showed that DA3/R848/OVA could activate DCs better than OVA or OVA + R848. Furthermore, the nanovaccine demonstrated a strong therapeutic effect by significantly suppressing tumor growth in a B16-OVA melanoma model. Additionally, prophylactic immunization with the nanovaccine effectively induced immunological memory, leading to sustained tumor suppression upon challenge. Intranasal delivery of DA3/R848/OVA upregulates the antitumor effect in the metastatic lung tumor foci and the survival rates. These results suggest that intranasal immunization using the DA3/R848/OVA nanovaccine can promote needle-free vaccination.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123331"},"PeriodicalIF":12.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-12DOI: 10.1016/j.biomaterials.2025.123340
Yan Feng , Junjun Ni , Huilin Xie , Na Zhu , Wenjing Liu , Liang Guo , Jianquan Zhang , Jia Di , Shuixiang He , Hao Hu , Hui Xing , Feng Xu , Guorui Jin , Ben Zhong Tang , Xiaoran Yin
Organic photothermal agents (PTAs) with high photothermal conversion efficiency (PCE) and biocompatibility are ideal for mild photothermal therapy (PTT), which can selectively eliminate tumor cells and elicit an active immune response. However, the challenge lies in developing PTAs with high PCE, and the impact of PTT-induced temperature gradients on the cytolytic potential of natural killer (NK) cells against tumor cells has yet been investigated. Herein a novel NIR-II aggregation-induced emission (AIE) molecule named C12T-BBT is proposed by conjugating an electron donor TPA with a strong electron acceptor BBT, using a long alkyl chain (C12) substituted thiophene as π-bridge. By doing this, C12T-BBT has a relative planar structure to ensure a high extinction coefficient, while the long alkyl chain restricts the π-π interaction and provides more room for molecular motion in excited state. Together, these design strategies assure C12T-BBT with a high PCE of 84.7 %. In vivo experiments exhibit favorable NIR-II imaging and tumor elimination using water-soluble cRGD@C12T-BBT nanoparticles. The application of mild PTT results in an effective induction of NK cell response in terms of shortening its distance with tumor cells from 25.6 μm to 10.6 μm, characterized using a machine-learning based spatial analysis, thereby enhancing the efficacy of cancer therapy. Therefore, this work provides evidence for a novel combined anti-tumor strategy of aligning mild PTT and NK cell immunotherapy by illustrating crucial optimization of NK-tumor intercellular proximity in mild PTT.
{"title":"NIR-II AIEgen with high photothermal efficiency for mild PTT: Optimized natural killer cell spatial distribution for boosted immune response","authors":"Yan Feng , Junjun Ni , Huilin Xie , Na Zhu , Wenjing Liu , Liang Guo , Jianquan Zhang , Jia Di , Shuixiang He , Hao Hu , Hui Xing , Feng Xu , Guorui Jin , Ben Zhong Tang , Xiaoran Yin","doi":"10.1016/j.biomaterials.2025.123340","DOIUrl":"10.1016/j.biomaterials.2025.123340","url":null,"abstract":"<div><div>Organic photothermal agents (PTAs) with high photothermal conversion efficiency (PCE) and biocompatibility are ideal for mild photothermal therapy (PTT), which can selectively eliminate tumor cells and elicit an active immune response. However, the challenge lies in developing PTAs with high PCE, and the impact of PTT-induced temperature gradients on the cytolytic potential of natural killer (NK) cells against tumor cells has yet been investigated. Herein a novel NIR-II aggregation-induced emission (AIE) molecule named C12T-BBT is proposed by conjugating an electron donor TPA with a strong electron acceptor BBT, using a long alkyl chain (C12) substituted thiophene as <em>π</em>-bridge. By doing this, C12T-BBT has a relative planar structure to ensure a high extinction coefficient, while the long alkyl chain restricts the <em>π-π</em> interaction and provides more room for molecular motion in excited state. Together, these design strategies assure C12T-BBT with a high PCE of 84.7 %. In vivo experiments exhibit favorable NIR-II imaging and tumor elimination using water-soluble cRGD@C12T-BBT nanoparticles. The application of mild PTT results in an effective induction of NK cell response in terms of shortening its distance with tumor cells from 25.6 μm to 10.6 μm, characterized using a machine-learning based spatial analysis, thereby enhancing the efficacy of cancer therapy. Therefore, this work provides evidence for a novel combined anti-tumor strategy of aligning mild PTT and NK cell immunotherapy by illustrating crucial optimization of NK-tumor intercellular proximity in mild PTT.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123340"},"PeriodicalIF":12.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-12DOI: 10.1016/j.biomaterials.2025.123329
Ying Lyu , Qichuan Yin , Xiaodan Liao , Youxuan Xie , Hao Yang , Yilei Cui , Yuqi Han , Ke Yao , Chunru Wang , Xingchao Shentu
Dry eye disease (DED) affects up to 50 % of the global population, leading to serious discomforts that affect patients’ quality of life. In the multifactorial etiology of DED, oxidative stress is at the core, initiating a sequence of inflammatory responses and surface damage via a vicious cycle. However, current therapies merely have a narrow focus on inflammation. In this study, we developed a novel antioxidative eye drop, ethylenediamine (EDA)-modified C70 fullerene derivatives (abbreviated as FN-EDA), to break this vicious cycle. FN-EDA was successfully synthesized by modifying C70 fullerene with multiple ethylenediamine (EDA) groups, resulting in enhanced water solubility and a positive charge. This modification significantly improved ocular surface retention time, cellular uptake, and lysosomal escape in vitro. Therapeutically, FN-EDA significantly alleviated dry eye disease (DED) in a mouse model. It reduced corneal epithelial damage by 3.8-fold compared to 0.05 % cyclosporine A (CsA) and restored tear secretion to approximately 65 % of the normal level. Mechanistically, both in vivo and in vitro results demonstrate that FN-EDA is endowed with superior biological activity in effectively scavenging excessive oxidative stress, down-regulating proinflammatory cytokines expression, and promoting epithelial barrier reconstruction, even recovering corneal innervation. Thus, our findings open an avenue to make this multi-functional eye drop a promising candidate for DED.
{"title":"Aminated fullerene for comprehensive dry eye therapy: Promoting epithelial-barrier reconstruction and nerve regeneration by suppressing oxidation and inflammation","authors":"Ying Lyu , Qichuan Yin , Xiaodan Liao , Youxuan Xie , Hao Yang , Yilei Cui , Yuqi Han , Ke Yao , Chunru Wang , Xingchao Shentu","doi":"10.1016/j.biomaterials.2025.123329","DOIUrl":"10.1016/j.biomaterials.2025.123329","url":null,"abstract":"<div><div>Dry eye disease (DED) affects up to 50 % of the global population, leading to serious discomforts that affect patients’ quality of life. In the multifactorial etiology of DED, oxidative stress is at the core, initiating a sequence of inflammatory responses and surface damage via a vicious cycle. However, current therapies merely have a narrow focus on inflammation. In this study, we developed a novel antioxidative eye drop, ethylenediamine (EDA)-modified C<sub>70</sub> fullerene derivatives (abbreviated as FN-EDA), to break this vicious cycle. FN-EDA was successfully synthesized by modifying C<sub>70</sub> fullerene with multiple ethylenediamine (EDA) groups, resulting in enhanced water solubility and a positive charge. This modification significantly improved ocular surface retention time, cellular uptake, and lysosomal escape <em>in vitro</em>. Therapeutically, FN-EDA significantly alleviated dry eye disease (DED) in a mouse model. It reduced corneal epithelial damage by 3.8-fold compared to 0.05 % cyclosporine A (CsA) and restored tear secretion to approximately 65 % of the normal level. Mechanistically, both <em>in vivo</em> and <em>in vitro</em> results demonstrate that FN-EDA is endowed with superior biological activity in effectively scavenging excessive oxidative stress, down-regulating proinflammatory cytokines expression, and promoting epithelial barrier reconstruction, even recovering corneal innervation. Thus, our findings open an avenue to make this multi-functional eye drop a promising candidate for DED.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"321 ","pages":"Article 123329"},"PeriodicalIF":12.8,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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