Pub Date : 2025-12-12DOI: 10.1016/j.biomaterials.2025.123903
So-Hyeon Park , Gaeun Ma , Seong Jin Park , Seong-Bin Yang , Minho Seo , Jun-Hyuck Lee , Seho Kweon , Jooho Park
The development of charge-based self-assembled supramolecules can provide a groundbreaking advancement in the oral delivery of nanoparticles. In this study, we developed a series of positively charged peptide-engineered bile acids (PCBs) for the first time to interact with the negatively charged semaglutide (SG), a widely used Glucagon-like peptide-1 (GLP-1) receptor agonist for the treatment of obesity and diabetes. Among the synthesized PCBs, PCB4 self-assembled with semaglutide via electrostatic interactions to form stable supramolecular nanoparticles, termed positively charged bile acid-saturated semaglutide (PBSG) nanocomplexes, with an average size of approximately 279 nm under aqueous conditions. These PBSG nanocomplexes demonstrated enhanced permeability and absorption through bile acid transporter-driven endocytosis in intestinal cells and tissues, inducing natural breakdown of cell membranes. Notably, PBSG nanocomplex increased the gastrointestinal (GI) permeation and oral absorption of semaglutide, improved therapeutic efficacy in a high-fat diet (HFD)-induced animal model, and inhibited bile acid transporter activity. Moreover, Oral PBSG nanocomplex treatment elevated GLP-1 expression in vivo by facilitating semaglutide delivery and modulating bile acid metabolism at the same time. The development of these novel, charge-based, self-assembling oral peptide nanocomplexes, leveraging positively charged bile acids and transporter-driven uptake, represents a significant advancement in oral nanoparticle delivery and the design of therapeutic nanomaterials.
{"title":"Charge-based supramolecular peptide nanocomplexes for oral delivery via transporter-driven endocytosis","authors":"So-Hyeon Park , Gaeun Ma , Seong Jin Park , Seong-Bin Yang , Minho Seo , Jun-Hyuck Lee , Seho Kweon , Jooho Park","doi":"10.1016/j.biomaterials.2025.123903","DOIUrl":"10.1016/j.biomaterials.2025.123903","url":null,"abstract":"<div><div>The development of charge-based self-assembled supramolecules can provide a groundbreaking advancement in the oral delivery of nanoparticles. In this study, we developed a series of positively charged peptide-engineered bile acids (PCBs) for the first time to interact with the negatively charged semaglutide (SG), a widely used Glucagon-like peptide-1 (GLP-1) receptor agonist for the treatment of obesity and diabetes. Among the synthesized PCBs, PCB<sub>4</sub> self-assembled with semaglutide via electrostatic interactions to form stable supramolecular nanoparticles, termed positively charged bile acid-saturated semaglutide (PBSG) nanocomplexes, with an average size of approximately 279 nm under aqueous conditions. These PBSG nanocomplexes demonstrated enhanced permeability and absorption through bile acid transporter-driven endocytosis in intestinal cells and tissues, inducing natural breakdown of cell membranes. Notably, PBSG nanocomplex increased the gastrointestinal (GI) permeation and oral absorption of semaglutide, improved therapeutic efficacy in a high-fat diet (HFD)-induced animal model, and inhibited bile acid transporter activity. Moreover, Oral PBSG nanocomplex treatment elevated GLP-1 expression <em>in vivo</em> by facilitating semaglutide delivery and modulating bile acid metabolism at the same time. The development of these novel, charge-based, self-assembling oral peptide nanocomplexes, leveraging positively charged bile acids and transporter-driven uptake, represents a significant advancement in oral nanoparticle delivery and the design of therapeutic nanomaterials.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123903"},"PeriodicalIF":12.9,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760483","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 : 2025-12-12DOI: 10.1016/j.biomaterials.2025.123921
Hang Dong , Tongtong Zhu , Yirong Sun , Jiazhen Yang , Guangyao Liu , Guoliang Wang , Jianxun Ding
Several pathological mechanisms, including vascular endothelial cell injury, osteocyte apoptosis, and excessive osteoclast activation, drive osteonecrosis. The disease progression is further exacerbated by disrupted bone remodeling, immune system dysregulation, and impaired regeneration capacity of blood vessel and bone. In weight-bearing joints, progressive subchondral bone deterioration often leads to joint collapse, resulting in chronic pain, stiffness, and disability. Early intervention, typically involving core decompression combined with bone grafting, is essential to prevent irreversible joint damage. Due to the limited availability of autologous bone, research has increasingly focused on developing advanced artificial bone substitutes. This review systematically summarizes current biomaterial-based strategies for treating osteonecrosis, emphasizing innovative approaches that enhance vascular regeneration and osteogenesis while simultaneously suppressing osteoclast activity and modulating immune responses. It also provides an overview of osteogenic biomaterial fabrication and the mechanisms by which biomaterials mediate tissue regeneration, emerging trends in bioactive material development, and potential strategies for advancing next-generation biomaterials.
{"title":"Bone microenvironments-regulated biomaterials boost osteonecrosis therapy","authors":"Hang Dong , Tongtong Zhu , Yirong Sun , Jiazhen Yang , Guangyao Liu , Guoliang Wang , Jianxun Ding","doi":"10.1016/j.biomaterials.2025.123921","DOIUrl":"10.1016/j.biomaterials.2025.123921","url":null,"abstract":"<div><div>Several pathological mechanisms, including vascular endothelial cell injury, osteocyte apoptosis, and excessive osteoclast activation, drive osteonecrosis. The disease progression is further exacerbated by disrupted bone remodeling, immune system dysregulation, and impaired regeneration capacity of blood vessel and bone. In weight-bearing joints, progressive subchondral bone deterioration often leads to joint collapse, resulting in chronic pain, stiffness, and disability. Early intervention, typically involving core decompression combined with bone grafting, is essential to prevent irreversible joint damage. Due to the limited availability of autologous bone, research has increasingly focused on developing advanced artificial bone substitutes. This review systematically summarizes current biomaterial-based strategies for treating osteonecrosis, emphasizing innovative approaches that enhance vascular regeneration and osteogenesis while simultaneously suppressing osteoclast activity and modulating immune responses. It also provides an overview of osteogenic biomaterial fabrication and the mechanisms by which biomaterials mediate tissue regeneration, emerging trends in bioactive material development, and potential strategies for advancing next-generation biomaterials.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123921"},"PeriodicalIF":12.9,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877537","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 : 2025-12-12DOI: 10.1016/j.biomaterials.2025.123916
Yu-Ting Li , Tian-Ci Wei , Jun-Xiao Yuan , Jia-Qi Feng , Pei-Pei Yang , Shu-Sheng Tang , Lei Wang , Hao Wang
Anti-Gram-positive bacteria, including multidrug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA), face significant challenges due to their robust cell wall structures, biofilm formation, and resistance mechanisms. Natural antimicrobial peptides (NAMPs) with a long history of development and wide use in clinical applications demonstrate broad-spectrum antibacterial activities through multi-target mechanisms, including disrupting bacterial cell walls and membranes. Owing to methodological limitations, conventional approaches for discovering NAMPs are becoming less effective in identifying new candidates. Therefore, biomimetic antimicrobial peptides (BAMPs) have been developed through structural modifications to enhance stability, safety, and antimicrobial efficacy. This review systematically summarizes recent advances in NAMPs and BAMPs against Gram-positive bacteria, and describes their mechanisms of action, including targeting peptidoglycan precursors in bacterial cell walls, disrupting membrane integrity, and interfering with DNA/RNA to inhibit bacterial growth. This review emphasizes the bacterial trapping mechanism via in situ self-assembly. We also highlight molecular modifications to optimize BAMPs that improve their antimicrobial potential and expand their application in clinic. Finally, we discuss the current limitations and future perspectives of NAMPs and BAMPs, provide valuable guidance for designing next-generation antimicrobial agents.
{"title":"Biomimetic antimicrobial peptides against gram-positive bacteria","authors":"Yu-Ting Li , Tian-Ci Wei , Jun-Xiao Yuan , Jia-Qi Feng , Pei-Pei Yang , Shu-Sheng Tang , Lei Wang , Hao Wang","doi":"10.1016/j.biomaterials.2025.123916","DOIUrl":"10.1016/j.biomaterials.2025.123916","url":null,"abstract":"<div><div>Anti-Gram-positive bacteria, including multidrug-resistant strains such as methicillin-resistant <em>S</em><em>taphylococcus aureus</em> (MRSA), face significant challenges due to their robust cell wall structures, biofilm formation, and resistance mechanisms. Natural antimicrobial peptides (NAMPs) with a long history of development and wide use in clinical applications demonstrate broad-spectrum antibacterial activities through multi-target mechanisms, including disrupting bacterial cell walls and membranes. Owing to methodological limitations, conventional approaches for discovering NAMPs are becoming less effective in identifying new candidates. Therefore, biomimetic antimicrobial peptides (BAMPs) have been developed through structural modifications to enhance stability, safety, and antimicrobial efficacy. This review systematically summarizes recent advances in NAMPs and BAMPs against Gram-positive bacteria, and describes their mechanisms of action, including targeting peptidoglycan precursors in bacterial cell walls, disrupting membrane integrity, and interfering with DNA/RNA to inhibit bacterial growth. This review emphasizes the bacterial trapping mechanism via in situ self-assembly. We also highlight molecular modifications to optimize BAMPs that improve their antimicrobial potential and expand their application in clinic. Finally, we discuss the current limitations and future perspectives of NAMPs and BAMPs, provide valuable guidance for designing next-generation antimicrobial agents.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123916"},"PeriodicalIF":12.9,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760544","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}
The osteosarcoma tumor microenvironment (OS-TME) exhibits pronounced cellular and biophysical heterogeneity, arising from infiltrating immune cells, primarily tumor-associated macrophages (TAMs) and mechanical stress gradients, respectively. TAMs significantly contribute to OS progression through various mechanisms; hence, targeting TAMs could improve treatment outcome in OS patients. This study presents a novel immunocompetent tri-culture osteosarcoma (iTC-OS) model developed using a porous 3D silk fibroin blend-hydroxyapatite (SF-HA) scaffold seeded with human OS cells, human blood derived TAMs, and human umbilical vein endothelial cells (HUVECs). The physiological relevance of the iTC-OS model is further enhanced by integrating into a physiomimetic microfluidic bioreactor (iTC-OS-on-a-chip), featuring dynamic perfusion to simulate intra-tumoral mechanical stress gradient, validated through computational fluid dynamic (CFD). Additionally, we employed pexidartinib and tenalisib to evaluate TAMs reversal in the iTC-OS-on-a-chip model by selectively inhibiting CSF1R and PI3Kγ, respectively. TAMs reprogramming from tumor promoting M2 to tumor suppressing M1 phenotype is confirmed through gene expression analysis of M1 (CCR7, IL-1β, IL-6) and M2 (CD206, CD163, IL-10) macrophage markers, alongside quantification of secreted cytokines via ELISA assay. This advanced iTC-OS-on-a-chip model offers a robust platform for investigating OS-immune cell interactions, enabling pre-clinical evaluation of chemo/immunotherapeutics and improving the translational relevance in OS research.
骨肉瘤肿瘤微环境(OS-TME)表现出明显的细胞和生物物理异质性,分别由浸润性免疫细胞、主要是肿瘤相关巨噬细胞(tam)和机械应力梯度引起。tam通过各种机制显著促进操作系统的发展;因此,靶向tam可以改善OS患者的治疗效果。本研究提出了一种新型的免疫活性三培养骨肉瘤(tc -OS)模型,该模型使用多孔3D丝素蛋白-羟基磷灰石(SF-HA)支架,植入人骨肉瘤细胞、人血源性tam和人脐静脉内皮细胞(HUVECs)。通过集成仿生微流控生物反应器(tc - os -on-a-chip),进一步增强了tc - os模型的生理相关性,该微流控生物反应器采用动态灌注模拟肿瘤内机械应力梯度,并通过计算流体动力学(CFD)验证。此外,我们使用培西达替尼和tenalisib分别通过选择性抑制CSF1R和PI3Kγ来评估tc - os -on-a-chip模型中的tam逆转。通过对M1 (CCR7、IL-1β、IL-6)和M2 (CD206、CD163、IL-10)巨噬细胞标志物的基因表达分析,以及通过ELISA法定量分泌的细胞因子,证实了tam从促肿瘤M2表型重编程为抑肿瘤M1表型。这种先进的tc -OS-on-a-chip模型为研究OS-免疫细胞相互作用提供了一个强大的平台,使化疗/免疫治疗的临床前评估成为可能,并提高了OS研究的翻译相关性。
{"title":"Osteosarcoma-on-a-chip model mimicking intra-tumoral heterogeneity to interrogate tumor-associated macrophage reprogramming for immunotherapeutics","authors":"Chitra Jaiswal , Saki Sugihara , Souradeep Dey , Ajay Kumar , Arpita Sharma , Raghvendra Gupta , Biman B. Mandal","doi":"10.1016/j.biomaterials.2025.123917","DOIUrl":"10.1016/j.biomaterials.2025.123917","url":null,"abstract":"<div><div>The osteosarcoma tumor microenvironment (OS-TME) exhibits pronounced cellular and biophysical heterogeneity, arising from infiltrating immune cells, primarily tumor-associated macrophages (TAMs) and mechanical stress gradients, respectively. TAMs significantly contribute to OS progression through various mechanisms; hence, targeting TAMs could improve treatment outcome in OS patients. This study presents a novel immunocompetent tri-culture osteosarcoma (iTC-OS) model developed using a porous 3D silk fibroin blend-hydroxyapatite (SF-HA) scaffold seeded with human OS cells, human blood derived TAMs, and human umbilical vein endothelial cells (HUVECs). The physiological relevance of the iTC-OS model is further enhanced by integrating into a physiomimetic microfluidic bioreactor (iTC-OS-on-a-chip), featuring dynamic perfusion to simulate intra-tumoral mechanical stress gradient, validated through computational fluid dynamic (CFD). Additionally, we employed pexidartinib and tenalisib to evaluate TAMs reversal in the iTC-OS-on-a-chip model by selectively inhibiting CSF1R and PI3Kγ, respectively. TAMs reprogramming from tumor promoting M2 to tumor suppressing M1 phenotype is confirmed through gene expression analysis of M1 (CCR7, IL-1β, IL-6) and M2 (CD206, CD163, IL-10) macrophage markers, alongside quantification of secreted cytokines via ELISA assay. This advanced iTC-OS-on-a-chip model offers a robust platform for investigating OS-immune cell interactions, enabling pre-clinical evaluation of chemo/immunotherapeutics and improving the translational relevance in OS research.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123917"},"PeriodicalIF":12.9,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145814847","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 : 2025-12-11DOI: 10.1016/j.biomaterials.2025.123912
Lisha Pan , Ao Zheng , Ning Huang , Shuning Zhang , Lingjie Peng , Fei Zheng , Lingyan Cao , Xiao Wang , Xinquan Jiang
Due to the increased risk of tooth loss associated with diabetes mellitus, patients exhibit a markedly higher demand for dental implant restoration. However, hyperglycemia and the accumulation of advanced glycation end-products (AGEs) induce oxidative stress, increase the risk of peri-implantitis, and impair osseointegration, posing significant challenges to the long-term success of implants. Moreover, the incorporation of antibacterial agents, while enhancing antibacterial efficacy, often elevates oxidative stress and compromises osteogenic capacity and cytocompatibility. Herein, a single-step fabricated bioactive protean TiO2/ZnO bio-heterojunction (BJ) system was developed on carbon-fiber-reinforced polyetheretherketone (CFRPEEK) implants to dynamically modulate diabetic microenvironment through multi-functional synergy (antibacterial/osteogenic/antioxidant). The CFRPEEK was firstly titanium plasma immersion ion implanted (PIIID-Ti) to obtain a micro-nanoscaled titanium dioxide (TiO2) interface. Sequentially, enhanced functionalities were attained by incorporating zinc oxide nanoparticles (ZnO NPs) to form TiO2/ZnO BJ through polydopamine (PDA) assisted π—π covalent immobilization. The results reveal that the TiO2/ZnO BJ effectively modulates reactive oxygen species (ROS) levels. The BJ PIIID-Ti surface exhibits excellent biocompatibility, osteo-inductive potential, and antibacterial efficacy during the early stage, while featuring a ROS scavenging function facilitated by PDA@ZnO NPs during the later stage. In vivo assessments further confirmed that the modified implants possess excellent biosafety, antibacterial ability and osseointegration capacity in the diabetic rat femoral defect model over six weeks. Moreover, the modified implants alleviated oxidative stress and improved the local regenerative microenvironment through activation of the Keap1/Nrf2 pathway. The BJ PIIID-Ti modified CFRPEEK implants demonstrate potential for combating diabetic infection and self-regulating oxidative stress for tissue protection, offering a theoretical basis for future clinical application.
{"title":"Protean bio-heterojunction nanoparticle coating for dynamically modulating diabetic microenvironment","authors":"Lisha Pan , Ao Zheng , Ning Huang , Shuning Zhang , Lingjie Peng , Fei Zheng , Lingyan Cao , Xiao Wang , Xinquan Jiang","doi":"10.1016/j.biomaterials.2025.123912","DOIUrl":"10.1016/j.biomaterials.2025.123912","url":null,"abstract":"<div><div>Due to the increased risk of tooth loss associated with diabetes mellitus, patients exhibit a markedly higher demand for dental implant restoration. However, hyperglycemia and the accumulation of advanced glycation end-products (AGEs) induce oxidative stress, increase the risk of peri-implantitis, and impair osseointegration, posing significant challenges to the long-term success of implants. Moreover, the incorporation of antibacterial agents, while enhancing antibacterial efficacy, often elevates oxidative stress and compromises osteogenic capacity and cytocompatibility. Herein, a single-step fabricated bioactive protean TiO<sub>2</sub>/ZnO bio-heterojunction (BJ) system was developed on carbon-fiber-reinforced polyetheretherketone (CFRPEEK) implants to dynamically modulate diabetic microenvironment through multi-functional synergy (antibacterial/osteogenic/antioxidant). The CFRPEEK was firstly titanium plasma immersion ion implanted (PIIID-Ti) to obtain a micro-nanoscaled titanium dioxide (TiO<sub>2</sub>) interface. Sequentially, enhanced functionalities were attained by incorporating zinc oxide nanoparticles (ZnO NPs) to form TiO<sub>2</sub>/ZnO BJ through polydopamine (PDA) assisted π—π covalent immobilization. The results reveal that the TiO<sub>2</sub>/ZnO BJ effectively modulates reactive oxygen species (ROS) levels. The BJ PIIID-Ti surface exhibits excellent biocompatibility, osteo-inductive potential, and antibacterial efficacy during the early stage, while featuring a ROS scavenging function facilitated by PDA@ZnO NPs during the later stage. <em>In vivo</em> assessments further confirmed that the modified implants possess excellent biosafety, antibacterial ability and osseointegration capacity in the diabetic rat femoral defect model over six weeks. Moreover, the modified implants alleviated oxidative stress and improved the local regenerative microenvironment through activation of the Keap1/Nrf2 pathway. The BJ PIIID-Ti modified CFRPEEK implants demonstrate potential for combating diabetic infection and self-regulating oxidative stress for tissue protection, offering a theoretical basis for future clinical application.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123912"},"PeriodicalIF":12.9,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760484","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 : 2025-12-11DOI: 10.1016/j.biomaterials.2025.123898
Hong Wang , Cong Xu , Hanfeng Qin , Yalin He , Yunshi Li , Yuejun Jiang , Junbin Gao , Ziwei Hu , Lu Liu , Jiamiao Jiang , Bin Chen , Fei Peng , Yingjia Li , Yingfeng Tu
Osteoarthritis (OA) is a multifactorial joint disorder characterized by articular cartilage degradation and progressive synovial inflammation. The dense and avascular nature of cartilage hinders the delivery efficiency of nanocarriers to their target cells, resulting in limited therapeutic efficacy in clinical trials. Here, we report the design of a Piezo-MnO2 motor for in situ reestablishment of the articular microenvironment by effectively degrading the local excess hydrogen peroxide in the OA microenvironment into oxygen. The generated oxygen ameliorates hypoxic conditions and acts as a propellant for nanomotor actuation, thereby enabling the motor to penetrate deeply into cartilage and synovium. Under mechanical stress induced by ultrasonic vibration, Piezo-MnO2 motors efficiently produced electrical signals via piezoelectric effect. This initiates an influx of extracellular calcium ions, which further upregulates the expression of transforming growth factors and drives cartilage repair. Recognized for its anti-inflammatory and antioxidant properties, the hydrogen produced by ultrasonic piezoelectric effect of the motors significantly diminishes the level of pro-inflammatory cytokines. The developed strategy facilitates rapid in situ cartilage regeneration and articular microenvironment modulation, offering a transformative alternative to conventional OA interventions.
{"title":"Piezoelectric nanomotors for active cartilage regeneration of osteoarthritis via ultrasonic vibration and water splitting","authors":"Hong Wang , Cong Xu , Hanfeng Qin , Yalin He , Yunshi Li , Yuejun Jiang , Junbin Gao , Ziwei Hu , Lu Liu , Jiamiao Jiang , Bin Chen , Fei Peng , Yingjia Li , Yingfeng Tu","doi":"10.1016/j.biomaterials.2025.123898","DOIUrl":"10.1016/j.biomaterials.2025.123898","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a multifactorial joint disorder characterized by articular cartilage degradation and progressive synovial inflammation. The dense and avascular nature of cartilage hinders the delivery efficiency of nanocarriers to their target cells, resulting in limited therapeutic efficacy in clinical trials. Here, we report the design of a Piezo-MnO<sub>2</sub> motor for in situ reestablishment of the articular microenvironment by effectively degrading the local excess hydrogen peroxide in the OA microenvironment into oxygen. The generated oxygen ameliorates hypoxic conditions and acts as a propellant for nanomotor actuation, thereby enabling the motor to penetrate deeply into cartilage and synovium. Under mechanical stress induced by ultrasonic vibration, Piezo-MnO<sub>2</sub> motors efficiently produced electrical signals via piezoelectric effect. This initiates an influx of extracellular calcium ions, which further upregulates the expression of transforming growth factors and drives cartilage repair. Recognized for its anti-inflammatory and antioxidant properties, the hydrogen produced by ultrasonic piezoelectric effect of the motors significantly diminishes the level of pro-inflammatory cytokines. The developed strategy facilitates rapid in situ cartilage regeneration and articular microenvironment modulation, offering a transformative alternative to conventional OA interventions.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123898"},"PeriodicalIF":12.9,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773100","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 : 2025-12-11DOI: 10.1016/j.biomaterials.2025.123910
Qiu Zeng , Yuan Guo , Anyu Yang , Jun Li
Venous thrombosis (VT), a serious cardiovascular disease, is commonly encountered across various clinical departments. Over the past decade, the negative role of inflammation in the formation and resolution of VT has become increasingly recognized, with numerous inflammation-related mechanisms in VT being revealed. Despite this understanding, traditional antithrombotic treatments for VT primarily focus on targeting coagulation and fibrinolysis, while inadequately addressing inflammation issues. As a result, these treatments face challenges such as limited efficacy and a high risk of bleeding. Against this backdrop, the versatile characteristics of nanomedicine offer promising solutions for treating VT and its accompanying inflammation issues, particularly in preventing premature drug degradation within circulation and facilitating on-demand drug delivery to disease sites. In addition, recent advances in biomimetic nanotechnology and stimuli-responsive systems have further propelled potential applications of nanomedicine in this area. In this context, this review discusses the rational design of nanomaterials, the optimization of targeted delivery approaches, the advancement of stimuli-responsive release strategies, and the integration of biomimetic nanotechnology, all from an inflammation-focused perspective. With these ongoing advancements, nanomedicine holds great promise for precise and comprehensive VT treatment.
{"title":"Nanomedicine for venous thrombosis: Insights from an inflammatory perspective","authors":"Qiu Zeng , Yuan Guo , Anyu Yang , Jun Li","doi":"10.1016/j.biomaterials.2025.123910","DOIUrl":"10.1016/j.biomaterials.2025.123910","url":null,"abstract":"<div><div>Venous thrombosis (VT), a serious cardiovascular disease, is commonly encountered across various clinical departments. Over the past decade, the negative role of inflammation in the formation and resolution of VT has become increasingly recognized, with numerous inflammation-related mechanisms in VT being revealed. Despite this understanding, traditional antithrombotic treatments for VT primarily focus on targeting coagulation and fibrinolysis, while inadequately addressing inflammation issues. As a result, these treatments face challenges such as limited efficacy and a high risk of bleeding. Against this backdrop, the versatile characteristics of nanomedicine offer promising solutions for treating VT and its accompanying inflammation issues, particularly in preventing premature drug degradation within circulation and facilitating on-demand drug delivery to disease sites. In addition, recent advances in biomimetic nanotechnology and stimuli-responsive systems have further propelled potential applications of nanomedicine in this area. In this context, this review discusses the rational design of nanomaterials, the optimization of targeted delivery approaches, the advancement of stimuli-responsive release strategies, and the integration of biomimetic nanotechnology, all from an inflammation-focused perspective. With these ongoing advancements, nanomedicine holds great promise for precise and comprehensive VT treatment.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"329 ","pages":"Article 123910"},"PeriodicalIF":12.9,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145831712","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}
Individuals with underlying chronic inflammatory conditions are prone to increased morbidity when posed with an additional inflammatory challenge such as an injury or infection. Numerous components of the immune system including immature neutrophils are thought to contribute to the increased morbidity, but ascribing causation remains challenging due to lack of preclinical models to test the contribution of individual components. Herein, we address this challenge by developing and using a mouse model of biomaterial (chitosan-microspheres) implantation, which results in a specific and pronounced expansion of circulating immature neutrophils that exhibit dysregulated effector functions as determined by single cell RNA sequencing and ex vivo functional assays. Next, in this chitosan-implant model, we pose a second inflammatory challenge involving acute lung injury and demonstrate that the immature neutrophils drive an increase in lung immunopathology. Blocking the migration of these immature neutrophils through the administration of therapeutic antibodies or their function using specific small molecule inhibitors, profoundly lowers the immunopathology caused by the inflammatory challenge. Together, these studies demonstrate the utility of a biomaterial-implant model to establish a causal link between immature neutrophils and increased immunopathology and provides insights into new therapeutic strategies for treating individuals with chronic inflammatory ailments.
{"title":"A biomaterial implant model demonstrates that immature neutrophils drive immunopathology following acute injury","authors":"Vinod Kumar Dorai , Alakesh Alakesh , Ranjitha Guttapadu , Shruthi Ksheera Sagar , Meghna Ravishankar Valakatte , Jayashree Vijaya Raghavan , Monisha Mohandas , Kalpana S R , Nagasuma Chandra , Siddharth Jhunjhunwala","doi":"10.1016/j.biomaterials.2025.123907","DOIUrl":"10.1016/j.biomaterials.2025.123907","url":null,"abstract":"<div><div>Individuals with underlying chronic inflammatory conditions are prone to increased morbidity when posed with an additional inflammatory challenge such as an injury or infection. Numerous components of the immune system including immature neutrophils are thought to contribute to the increased morbidity, but ascribing causation remains challenging due to lack of preclinical models to test the contribution of individual components. Herein, we address this challenge by developing and using a mouse model of biomaterial (chitosan-microspheres) implantation, which results in a specific and pronounced expansion of circulating immature neutrophils that exhibit dysregulated effector functions as determined by single cell RNA sequencing and ex vivo functional assays. Next, in this chitosan-implant model, we pose a second inflammatory challenge involving acute lung injury and demonstrate that the immature neutrophils drive an increase in lung immunopathology. Blocking the migration of these immature neutrophils through the administration of therapeutic antibodies or their function using specific small molecule inhibitors, profoundly lowers the immunopathology caused by the inflammatory challenge. Together, these studies demonstrate the utility of a biomaterial-implant model to establish a causal link between immature neutrophils and increased immunopathology and provides insights into new therapeutic strategies for treating individuals with chronic inflammatory ailments.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123907"},"PeriodicalIF":12.9,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754924","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 : 2025-12-11DOI: 10.1016/j.biomaterials.2025.123905
Xiaoxia Li , Sicheng Yan , Mingding Li , Renyuan Liu , Qiangbing Lu , Minghui Lu , Feng Bai , Qun-Dong Shen
Synaptic dysfunction and loss are central drivers of cognitive decline in Alzheimer's disease (AD), yet current therapeutic approaches targeting amyloid-β or tau pathology have largely failed to rescue synaptic function. Neural oscillations and synaptic plasticity are tightly coupled and underpin functional brain networks, suggesting that modulating oscillatory dynamics may offer new therapeutic avenues. Here, we developed a strategy for precise, non-genetic neuromodulation using focused ultrasound and piezoelectric Ba0.85Ca0.15Zr0.1Ti0.9O3 (BCZT) nanoparticles to generate targeted, gamma-frequency electromagnetic fields in the hippocampal CA3 subregion of early-stage AD mouse models. This rhythmic stimulation effectively restored impaired gamma oscillations, enhanced synaptic plasticity, and remodeled memory-related network connectivity, as validated by local field potential recordings, patch-clamp electrophysiology, and functional MRI. Mechanistically, we demonstrate that NF-κB transcription factor activation during rhythmic stimulation regulates AMPAR trafficking by balancing synaptic internalization and delivery, with concurrent upregulation of P300-mediated histone acetylation. Our findings establish a novel paradigm for spatially precise, periodic neuromodulation that restores hippocampal information processing and network function in early AD, highlighting the therapeutic potential of piezoelectric nanomaterials for neural circuit repair in AD and other neurodegenerative diseases characterized by impaired neural rhythms.
{"title":"Piezoelectric nanoparticle-driven rhythmic ultrasound neuromodulation for treatment of early-stage Alzheimer's disease","authors":"Xiaoxia Li , Sicheng Yan , Mingding Li , Renyuan Liu , Qiangbing Lu , Minghui Lu , Feng Bai , Qun-Dong Shen","doi":"10.1016/j.biomaterials.2025.123905","DOIUrl":"10.1016/j.biomaterials.2025.123905","url":null,"abstract":"<div><div>Synaptic dysfunction and loss are central drivers of cognitive decline in Alzheimer's disease (AD), yet current therapeutic approaches targeting amyloid-β or tau pathology have largely failed to rescue synaptic function. Neural oscillations and synaptic plasticity are tightly coupled and underpin functional brain networks, suggesting that modulating oscillatory dynamics may offer new therapeutic avenues. Here, we developed a strategy for precise, non-genetic neuromodulation using focused ultrasound and piezoelectric Ba<sub>0.85</sub>Ca<sub>0.15</sub>Zr<sub>0.1</sub>Ti<sub>0.9</sub>O<sub>3</sub> (BCZT) nanoparticles to generate targeted, gamma-frequency electromagnetic fields in the hippocampal CA3 subregion of early-stage AD mouse models. This rhythmic stimulation effectively restored impaired gamma oscillations, enhanced synaptic plasticity, and remodeled memory-related network connectivity, as validated by local field potential recordings, patch-clamp electrophysiology, and functional MRI. Mechanistically, we demonstrate that NF-κB transcription factor activation during rhythmic stimulation regulates AMPAR trafficking by balancing synaptic internalization and delivery, with concurrent upregulation of P300-mediated histone acetylation. Our findings establish a novel paradigm for spatially precise, periodic neuromodulation that restores hippocampal information processing and network function in early AD, highlighting the therapeutic potential of piezoelectric nanomaterials for neural circuit repair in AD and other neurodegenerative diseases characterized by impaired neural rhythms.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123905"},"PeriodicalIF":12.9,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732906","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 : 2025-12-11DOI: 10.1016/j.biomaterials.2025.123904
Hyun Tack Woo , Jinyoung Yun , Jaeyun Lee , Kang-Il Song , Hyung Joon Cha
Effective electrophysiological signal transmission is crucial for tissue regeneration, rehabilitation, and bioelectronic applications, particularly in electrically active tissues such as nerves and muscles. However, existing interface materials face significant limitations, including electrical insulation, instability under physiological conditions due to poor underwater adhesiveness, and incompatibility with irregular tissue surfaces. To address these issues, we propose a conductive bioglue (CBG) comprising hyaluronic acid (HA)-coated eutectic gallium indium (EGaIn) nanodroplets with bioengineered mussel adhesive protein (MAP). This water-immiscible liquid-state CBG undergoes in situ crosslinking electrically, exhibiting excellent adhesion to underwater tissue and metal surfaces, suitable mechanical properties, and robust electrical conductivity. In vivo evaluations demonstrated its ability to restore acute and sustained tissue function while enhancing bioelectronic interfacing. These findings underscore the potential of CBG as a promising biocompatible conductive adhesive interface material for efficient in vivo transmission of electrophysiological signals, offering transformative applications in tissue engineering and bioelectronic devices.
{"title":"In situ electrocrosslinkable and immiscible bioadhesive for robust underwater electrophysiological signal interfaces","authors":"Hyun Tack Woo , Jinyoung Yun , Jaeyun Lee , Kang-Il Song , Hyung Joon Cha","doi":"10.1016/j.biomaterials.2025.123904","DOIUrl":"10.1016/j.biomaterials.2025.123904","url":null,"abstract":"<div><div>Effective electrophysiological signal transmission is crucial for tissue regeneration, rehabilitation, and bioelectronic applications, particularly in electrically active tissues such as nerves and muscles. However, existing interface materials face significant limitations, including electrical insulation, instability under physiological conditions due to poor underwater adhesiveness, and incompatibility with irregular tissue surfaces. To address these issues, we propose a conductive bioglue (CBG) comprising hyaluronic acid (HA)-coated eutectic gallium indium (EGaIn) nanodroplets with bioengineered mussel adhesive protein (MAP). This water-immiscible liquid-state CBG undergoes <em>in situ</em> crosslinking electrically, exhibiting excellent adhesion to underwater tissue and metal surfaces, suitable mechanical properties, and robust electrical conductivity. In vivo evaluations demonstrated its ability to restore acute and sustained tissue function while enhancing bioelectronic interfacing. These findings underscore the potential of CBG as a promising biocompatible conductive adhesive interface material for efficient <em>in vivo</em> transmission of electrophysiological signals, offering transformative applications in tissue engineering and bioelectronic devices.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"328 ","pages":"Article 123904"},"PeriodicalIF":12.9,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754954","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}