Jing Zhang, Jiangchuan Yang, Ayijiamila Mohetaer, Xiajie Hu, Fuxiang Song
{"title":"Self-Powered Electrical Stimulation Strategies for Bone Regeneration","authors":"Jing Zhang, Jiangchuan Yang, Ayijiamila Mohetaer, Xiajie Hu, Fuxiang Song","doi":"10.1002/adtp.202500551","DOIUrl":"https://doi.org/10.1002/adtp.202500551","url":null,"abstract":"<div>\u0000 \u0000 <p>Endogenous bioelectric cues regulate bone growth, repair, and remodeling. Conventional electrical stimulation can accelerate healing but is limited by wired power delivery, bulky hardware, and imprecise dosing. Self-powered electrical stimulation converts mechanical, optical, thermal, magnetic, or biochemical energy into physiologically relevant electric fields and currents. Distinct from reviews that focus on a single modality or narrow device class, this review synthesizes materials, device architectures, and application considerations across piezoelectric and triboelectric nanogenerators, photoelectric platforms, magnetoelectric composites, thermoelectric systems, bioelectrets, and biofuel cells. It further summarizes how these systems modulate membrane potential and Ca<sup>2+</sup> signaling, activate osteogenic programs, and coordinate angiogenesis and immune regulation. Key barriers include charge or polarization retention in ionic media, durability of devices and packaging under cyclic loading, stable output under small strains and temperature gradients, manufacturability, and rigorous validation in large, load-bearing models; additional considerations include Magnetic Resonance Imaging compatibility and magnetic-field safety for magnetoelectric implants. To improve comparability, a minimum reporting set is emphasized to quantify in situ tissue–device interface dose (field, current, waveform, duty cycle) together with input energy and biological readouts. Future directions include materials-by-design, hybrid harvesters with integrated storage, closed-loop sensing and control, and patient-specific digital planning.</p>\u0000 </div>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"9 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147567560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Zhang, Jiangchuan Yang, Ayijiamila Mohetaer, Xiajie Hu, Fuxiang Song
{"title":"Self-Powered Electrical Stimulation Strategies for Bone Regeneration","authors":"Jing Zhang, Jiangchuan Yang, Ayijiamila Mohetaer, Xiajie Hu, Fuxiang Song","doi":"10.1002/adtp.202500551","DOIUrl":"https://doi.org/10.1002/adtp.202500551","url":null,"abstract":"<div>\u0000 \u0000 <p>Endogenous bioelectric cues regulate bone growth, repair, and remodeling. Conventional electrical stimulation can accelerate healing but is limited by wired power delivery, bulky hardware, and imprecise dosing. Self-powered electrical stimulation converts mechanical, optical, thermal, magnetic, or biochemical energy into physiologically relevant electric fields and currents. Distinct from reviews that focus on a single modality or narrow device class, this review synthesizes materials, device architectures, and application considerations across piezoelectric and triboelectric nanogenerators, photoelectric platforms, magnetoelectric composites, thermoelectric systems, bioelectrets, and biofuel cells. It further summarizes how these systems modulate membrane potential and Ca<sup>2+</sup> signaling, activate osteogenic programs, and coordinate angiogenesis and immune regulation. Key barriers include charge or polarization retention in ionic media, durability of devices and packaging under cyclic loading, stable output under small strains and temperature gradients, manufacturability, and rigorous validation in large, load-bearing models; additional considerations include Magnetic Resonance Imaging compatibility and magnetic-field safety for magnetoelectric implants. To improve comparability, a minimum reporting set is emphasized to quantify in situ tissue–device interface dose (field, current, waveform, duty cycle) together with input energy and biological readouts. Future directions include materials-by-design, hybrid harvesters with integrated storage, closed-loop sensing and control, and patient-specific digital planning.</p>\u0000 </div>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"9 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147567559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bhimankshi R. Wakde, Bhagyashri N. Nehete, Dilip L. Pawara, Anup A. Telgote, Rahul S. Tade
{"title":"Graphene-Based Nanomaterials in Immunotoxicological Evaluation: Insights Into Macrophage Polarization, Tissue Engineering, and Biomedical Applications","authors":"Bhimankshi R. Wakde, Bhagyashri N. Nehete, Dilip L. Pawara, Anup A. Telgote, Rahul S. Tade","doi":"10.1002/adtp.202500562","DOIUrl":"https://doi.org/10.1002/adtp.202500562","url":null,"abstract":"<div>\u0000 \u0000 <p>Graphene-based nanomaterials (GBNs) have emerged as promising platforms for biomedical applications, yet their clinical translation is largely governed by interactions with the immune system. Among immune cells, macrophages act as key regulators of the biological fate of GBNs through polarization toward pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes. This polarization is strongly influenced by the physicochemical properties of GBNs, including structural characteristics and surface chemistry, and directly impacts nanomaterial clearance, biodistribution, immunotoxicity, and therapeutic efficacy. This review synthesizes recent studies examining how GBN properties dictate macrophage polarization and the resulting immunological outcomes. Evidence from in vitro and in vivo investigations demonstrates that controlled macrophage responses can support beneficial effects such as tissue repair and cancer immunotherapy, whereas inappropriate activation may lead to oxidative stress, cytotoxicity, and adverse immune reactions. These findings highlight the dual role of macrophage polarization in mediating both therapeutic potential and immunotoxicity risk. We emphasize the need for standardized immunological assays and rational design strategies to predict and modulate macrophage responses to GBNs. A clearer understanding of the relationship between GBN physicochemical properties and macrophage polarization is essential for minimizing immunotoxicity while enabling safe and effective therapeutic applications.</p>\u0000 </div>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"9 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147565812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bhimankshi R. Wakde, Bhagyashri N. Nehete, Dilip L. Pawara, Anup A. Telgote, Rahul S. Tade
{"title":"Graphene-Based Nanomaterials in Immunotoxicological Evaluation: Insights Into Macrophage Polarization, Tissue Engineering, and Biomedical Applications","authors":"Bhimankshi R. Wakde, Bhagyashri N. Nehete, Dilip L. Pawara, Anup A. Telgote, Rahul S. Tade","doi":"10.1002/adtp.202500562","DOIUrl":"https://doi.org/10.1002/adtp.202500562","url":null,"abstract":"<div>\u0000 \u0000 <p>Graphene-based nanomaterials (GBNs) have emerged as promising platforms for biomedical applications, yet their clinical translation is largely governed by interactions with the immune system. Among immune cells, macrophages act as key regulators of the biological fate of GBNs through polarization toward pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes. This polarization is strongly influenced by the physicochemical properties of GBNs, including structural characteristics and surface chemistry, and directly impacts nanomaterial clearance, biodistribution, immunotoxicity, and therapeutic efficacy. This review synthesizes recent studies examining how GBN properties dictate macrophage polarization and the resulting immunological outcomes. Evidence from in vitro and in vivo investigations demonstrates that controlled macrophage responses can support beneficial effects such as tissue repair and cancer immunotherapy, whereas inappropriate activation may lead to oxidative stress, cytotoxicity, and adverse immune reactions. These findings highlight the dual role of macrophage polarization in mediating both therapeutic potential and immunotoxicity risk. We emphasize the need for standardized immunological assays and rational design strategies to predict and modulate macrophage responses to GBNs. A clearer understanding of the relationship between GBN physicochemical properties and macrophage polarization is essential for minimizing immunotoxicity while enabling safe and effective therapeutic applications.</p>\u0000 </div>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"9 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147565813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bhimankshi R. Wakde, Bhagyashri N. Nehete, Dilip L. Pawara, Anup A. Telgote, Rahul S. Tade
{"title":"Graphene-Based Nanomaterials in Immunotoxicological Evaluation: Insights Into Macrophage Polarization, Tissue Engineering, and Biomedical Applications","authors":"Bhimankshi R. Wakde, Bhagyashri N. Nehete, Dilip L. Pawara, Anup A. Telgote, Rahul S. Tade","doi":"10.1002/adtp.202500562","DOIUrl":"https://doi.org/10.1002/adtp.202500562","url":null,"abstract":"<div>\u0000 \u0000 <p>Graphene-based nanomaterials (GBNs) have emerged as promising platforms for biomedical applications, yet their clinical translation is largely governed by interactions with the immune system. Among immune cells, macrophages act as key regulators of the biological fate of GBNs through polarization toward pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes. This polarization is strongly influenced by the physicochemical properties of GBNs, including structural characteristics and surface chemistry, and directly impacts nanomaterial clearance, biodistribution, immunotoxicity, and therapeutic efficacy. This review synthesizes recent studies examining how GBN properties dictate macrophage polarization and the resulting immunological outcomes. Evidence from in vitro and in vivo investigations demonstrates that controlled macrophage responses can support beneficial effects such as tissue repair and cancer immunotherapy, whereas inappropriate activation may lead to oxidative stress, cytotoxicity, and adverse immune reactions. These findings highlight the dual role of macrophage polarization in mediating both therapeutic potential and immunotoxicity risk. We emphasize the need for standardized immunological assays and rational design strategies to predict and modulate macrophage responses to GBNs. A clearer understanding of the relationship between GBN physicochemical properties and macrophage polarization is essential for minimizing immunotoxicity while enabling safe and effective therapeutic applications.</p>\u0000 </div>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"9 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147565997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Akshay Krishnakumar, Alexander Roth, Praveen Srinivasan, Muhammad Masud Rana, Nicholas L. F. Gallina, Devendra Sarnaik, Robyn R. McCain, Abigail D. Cox, Mohamed N. Seleem, Arun K. Bhunia, Rahim Rahimi
{"title":"Smart Wearable Ozone Therapy System for Managing Multidrug-Resistant Wound Infections","authors":"Akshay Krishnakumar, Alexander Roth, Praveen Srinivasan, Muhammad Masud Rana, Nicholas L. F. Gallina, Devendra Sarnaik, Robyn R. McCain, Abigail D. Cox, Mohamed N. Seleem, Arun K. Bhunia, Rahim Rahimi","doi":"10.1002/adtp.202500541","DOIUrl":"https://doi.org/10.1002/adtp.202500541","url":null,"abstract":"<p>Multidrug-resistant (MDR) bacterial infections represent a critical challenge in wound care, leading to treatment failure, prolonged healing, and increased morbidity and mortality worldwide. Among MDR pathogens, <i>Pseudomonas aeruginosa</i> is particularly problematic due to its adaptive resistance mechanisms, underscoring the urgent need for alternative, non-antibiotic therapeutic strategies. Ozone has demonstrated potent antimicrobial efficacy while promoting wound healing and exhibiting a low propensity for resistance development; however, conventional ozone delivery systems are bulky, poorly suited for ambulatory use, and pose risks of environmental leakage and unintended exposure. To address these limitations, we have developed a smart wearable ozone therapy system capable of precise, localized ozone delivery directly to the wound bed. The platform integrates on-demand ozone generation, real-time sensing, and controlled air circulation within a compact, reusable unit, coupled to a disposable wound interface patch via double-lumen tubing. Embedded sensors continuously regulate ozone concentrations within therapeutic windows while detecting leakage and triggering automatic shutdown to ensure patient and environmental safety. System characterization demonstrated that localized low-level ozone exposure (75 ppm), when combined with Vancomycin (400 µg·mL<sup>−</sup><sup>1</sup>), eradicated planktonic bacterial cultures to undetectable levels within 4 h while maintaining minimal cytotoxicity toward mammalian cells. For the first time, this fully integrated wearable platform was validated in a <i>Pseudomonas aeruginosa–</i>infected porcine wound model, achieving approximately 90% bacterial reduction after four consecutive daily 6 h treatments and accelerating wound closure by nearly threefold compared with silver dressings or topical antibiotic treatment alone. These results establish a safe, effective, and translationally viable wearable ozone therapy system for the management of MDR-infected wounds.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"9 3","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202500541","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147564531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}