Maximilian Hammer, Lea Skrzypczyk, Sabrina Wohlfart, Bryan Calder Ackermann, Ludwig Geisweid, Simon William Pohl, Margarita Karaivanova, Jonathan Herth, Victor Aristide Augustin, Alexander Studier-Fischer, Tina Sackmann, Leon Kaulen, Anna Steyer, Walter Mier, David H Steel, Kanmin Xue, Gerd Uwe Auffarth, Philipp Uhl
{"title":"Methotrexate-Loaded Liposomal Formulation Enables 6-Week Sustained Intraocular Therapeutic Drug Release in a Porcine Model.","authors":"Maximilian Hammer, Lea Skrzypczyk, Sabrina Wohlfart, Bryan Calder Ackermann, Ludwig Geisweid, Simon William Pohl, Margarita Karaivanova, Jonathan Herth, Victor Aristide Augustin, Alexander Studier-Fischer, Tina Sackmann, Leon Kaulen, Anna Steyer, Walter Mier, David H Steel, Kanmin Xue, Gerd Uwe Auffarth, Philipp Uhl","doi":"10.1002/adhm.202503230","DOIUrl":"https://doi.org/10.1002/adhm.202503230","url":null,"abstract":"<p><p>Methotrexate (MTX) inhibits cell proliferation, which underlies ocular diseases, including intraocular lymphoma and proliferative vitreoretinopathy. However, MTX normally requires bi-weekly intravitreal injections due to a short half-life, causing rapid clearance below therapeutic thresholds within 72h. To overcome these limitations, sustained-release carriers, including poly(lactic-co-glycolic) acid-based implants, were investigated in vitro previously. These systems offer prolonged drug delivery but require relatively large-gauge surgical implantation, which increases the risk of surgical complications and limits their practical use. In this study, MTX-loaded liposomes that can be administered via a 30-gauge cannula are developed, obviating the need for more invasive surgical implantation. This phospholipid-based liposomal formulation succeeded in enabling sustained methotrexate release at therapeutic levels for over six weeks following a single intravitreal injection, demonstrated in vivo in a large animal pig model. High biocompatibility of this novel liposomal formulation is confirmed through longitudinal retinal structure (optical coherence tomography) and function (electroretinography) assessments. This liposomal formulation of MTX provides a clinically and surgically optimized drug delivery system that allows improved management of intraocular lymphoma and proliferative vitreoretinopathy in the future.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03230"},"PeriodicalIF":9.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ilayda Namli, Deepak Gupta, Yogendra Pratap Singh, Pallab Datta, Muhammad Rizwan, Mehmet Baykara, Ibrahim T Ozbolat
{"title":"Progressive Insights into 3D Bioprinting for Corneal Tissue Restoration.","authors":"Ilayda Namli, Deepak Gupta, Yogendra Pratap Singh, Pallab Datta, Muhammad Rizwan, Mehmet Baykara, Ibrahim T Ozbolat","doi":"10.1002/adhm.202503372","DOIUrl":"https://doi.org/10.1002/adhm.202503372","url":null,"abstract":"<p><p>The complex architecture of the cornea, characterized by specifically organized collagen fibrils and distinct cellular layers, poses significant challenges for traditional tissue engineering strategies to replicate its native function. 3D Bioprinting offers a promising solution by enabling the precise, layer-by-layer fabrication of corneal tissues, closely mimicking the essential characteristics needed for vision restoration and long-term graft success. This Review critically examines the key biomechanical, optical, and structural attributes of the cornea necessary for its effective engineering and accurate 3D bioprinting. It provides a comprehensive overview of different 3D bioprinting modalities utilized for corneal tissue engineering and offers insights into potential improvements. Additionally, it details the requirements for a corneal bioink suitable for 3D bioprinting, ensuring it meets the necessary corneal functions. The Review also delves into the current challenges in 3D bioprinting of corneal tissue and proposes potential solutions to successfully replicate the complex architecture and function of the cornea. Furthermore, it explores innovative approaches such as the use of induced pluripotent stem cells, gene therapy, and cornea-on-a-chip technologies, which hold promise for advancing corneal regeneration. The Review aims to visualize the future of corneal 3D bioprinting and the potential of integrating it with other techniques. Lastly, the review discusses clinical implications, emphasizing the potential of bioprinted corneal implants to address the global donor cornea shortage and significantly improve patient outcomes.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03372"},"PeriodicalIF":9.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Micaila DE Curtis, Yoontae Kim, Rahul Patil, Xinran Zhang, Meth Jayatilake, Orelle Bulgin, Peter Lialios, Sana Surrency, Soraya Tarrah, Argyris K Lazaris, Alison Grafton, James Williams, Seyedeh Boshra Nouraie, Maria Bizaki, Penelope Xeron, Edward Van Keuren, Jonathan E Seppala, Evagelia C Laiakis, Joanna B Kitlinska, Stella Alimperti
{"title":"Ascorbic Acid Modulates Collagen Properties in Glucocorticoid-Induced Osteoporotic Bone: Insights into Chemical, Mechanical, and Biological Regulation.","authors":"Micaila DE Curtis, Yoontae Kim, Rahul Patil, Xinran Zhang, Meth Jayatilake, Orelle Bulgin, Peter Lialios, Sana Surrency, Soraya Tarrah, Argyris K Lazaris, Alison Grafton, James Williams, Seyedeh Boshra Nouraie, Maria Bizaki, Penelope Xeron, Edward Van Keuren, Jonathan E Seppala, Evagelia C Laiakis, Joanna B Kitlinska, Stella Alimperti","doi":"10.1002/adhm.202502606","DOIUrl":"https://doi.org/10.1002/adhm.202502606","url":null,"abstract":"<p><p>Osteoporosis is a prevalent skeletal disorder characterized by decreased bone mass and structural deterioration, leading to an increased risk of fractures. This study focuses on the regulatory role of Vitamin C (ascorbic acid; AA) in the context of glucocorticoid-induced osteoporosis (GIOP), which results from long-term glucocorticoid (GC) therapy. The data showed that GCs impair AA metabolism in osteoblasts, thereby disrupting collagen synthesis and compromising extracellular matrix (ECM) integrity. Notably, AA integration in the collagen matrix improved its biochemical and mechanical properties. Additionally, it has been shown that the presence of AA restored osteoblast and endothelial function, enhanced collagen production, and improved endothelial barrier function under GC exposure. These results underscore the critical role of Vitamin C in bone matrix maintenance and homeostasis. Collectively, this work highlights the therapeutic potential of Vitamin C as a supportive treatment to counteract the deleterious skeletal effects of long-term GC therapy.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02606"},"PeriodicalIF":9.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenqiang Ma, Rui Ding, Siyuan Wang, Zengrong Wang, Letian Xu, Kun Zhou, Jinlu Ma, Gang He
{"title":"On-Site Visualized Periodontitis Screening via Dual-Signal H<sub>2</sub>S Probe.","authors":"Wenqiang Ma, Rui Ding, Siyuan Wang, Zengrong Wang, Letian Xu, Kun Zhou, Jinlu Ma, Gang He","doi":"10.1002/adhm.202502710","DOIUrl":"https://doi.org/10.1002/adhm.202502710","url":null,"abstract":"<p><p>Periodontitis is a destructive disease that causes irreversible damage to periodontal supporting tissues, posing a serious threat to patients' oral health. Given the insidious nature of periodontal tissue destruction, early diagnosis of periodontitis is crucial. Salivary hydrogen sulfide (H<sub>2</sub>S) has been identified as a potential biomarker for periodontitis monitoring. However, existing detection methods struggle to precisely locate the source of H<sub>2</sub>S release within the oral cavity, making it difficult to accurately identify affected areas and significantly hindering early diagnosis and treatment of periodontitis. This study reports a visual aggregation-induced emission (AIE) fluorescent probe (TTN), which exhibits high sensitivity and rapid responsiveness to H<sub>2</sub>S, along with dual-signal response capabilities in color and fluorescence. Based on this probe, a highly reliable and practical TTN film sensor capable of efficiently monitoring H<sub>2</sub>S is developed. The film can be used for real-time diagnosis of periodontitis, allowing precise identification of diseased tooth areas through visible color and fluorescence changes. Additionally, the film demonstrates efficient reactive oxygen species (ROS) generation, inhibiting the growth of periodontitis-causing bacteria and showcasing therapeutic potential. This integrated diagnostic and therapeutic design not only provides a novel approach for monitoring H<sub>2</sub>S as a biomarker but also opens new avenues for precise diagnosis and treatment of periodontitis.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02710"},"PeriodicalIF":9.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammad Asadi Tokmedash, Jacob Robins, J Scott VanEpps, Minji Kim, Jouha Min
{"title":"Multiscale Hybrid Surface Topographies Orchestrate Immune Regulation, Antibacterial Defense, and Tissue Regeneration.","authors":"Mohammad Asadi Tokmedash, Jacob Robins, J Scott VanEpps, Minji Kim, Jouha Min","doi":"10.1002/adhm.202502451","DOIUrl":"https://doi.org/10.1002/adhm.202502451","url":null,"abstract":"<p><p>Implant-associated complications-including infection, adverse immune responses, and poor tissue integration-pose significant risks to patients, often leading to implant failure, revision surgeries, or chronic disease. Current chemical-based strategies, such as antibiotic or drug-releasing systems, are limited by short-term efficacy, narrow therapeutic windows, and potential toxicity. Surface topography offers a promising alternative, but most designs target single cell types and overlook the complex, multicellular dynamics at the implant-host interface. Here, a new multifunctional platform is introduced based on nano-micro hybrid wrinkled topographies fabricated via a custom nanofabrication method that combines layer-by-layer (LbL) self-assembly with mechanical nanomanufacturing. This system simultaneously modulates bacteria, immune cells, and tissue progenitors to enable antibacterial activity, immune regulation, and tissue regeneration. On hybrid surfaces, nanoscale features disrupt bacterial adhesion (>50% biofilm reduction vs. flat controls), while microscale features enhance macrophage polarization (≈3-fold increase in M2 markers) and osteogenic differentiation (>8-fold increase in ALP activity), indicating strong pro-healing responses. Notably, macrophages exhibit context-dependent behavior-driving inflammation during bacterial infection and repair in its absence-creating an immune-balanced microenvironment for implant integration. The modular nature of this platform allows expansion to other cell types and disease contexts, offering a broadly applicable strategy for next-generation biomaterials.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02451"},"PeriodicalIF":9.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting PIN1 in Pancreatic Tumor Microenvironment with Peptide Amphiphiles Unleashes Immune Checkpoint Therapy.","authors":"Yuanyuan Wu, Jianan Guo, Yuwei Zhang, Ruizhi Zhao, Wenhao Luo, Chihua Fang","doi":"10.1002/adhm.202503114","DOIUrl":"https://doi.org/10.1002/adhm.202503114","url":null,"abstract":"<p><p>Pancreatic cancer (PC) is a highly aggressive malignancy with a dismal 5-year survival rate of only 12%. Currently, no effective therapeutic strategies can improve the prognosis of pancreatic cancer. The activation of quiescent pancreatic stellate cells (PSCs) and their crosstalk with pancreatic cancer cells (PCCs) lead to the formation of a fibrotic physical barrier and an immunosuppressive tumor microenvironment (TME), which severely impede drug delivery and penetration. To improve PC treatment, a dual-targeting strategy capable of simultaneously acting on PCCs and PSCs is urgently needed to revert activated PSCs (aPSCs) to their quiescent state and suppress the proliferation of PCCs. KPT-6566, a small-molecule inhibitor, shifts PSCs from an activated to a quiescent state, reprograms the tumor immune microenvironment (TIME) to enhance anti-PD-L1 immunotherapy efficacy, suppresses PCCs proliferation, and induces PD-L1 expression on PCC surfaces, thereby increasing sensitivity to PD-L1-targeted therapies. This study designs two amphiphilic peptides, C16-LLGG-COO-<sup>D</sup>PPA-1(DPPA-1@PA) and DSPE-PEG-NHS-CGKRK(CGKRK@PA), which can co-assemble to encapsulate KPT-6566 and finally form a peptide-based nanoparticle termed DP-KPT-CG@PA. This nanoparticle precisely targets PCCs and PSCs to co-deliver KPT-6566, while synergizing with a PD-L1-blocking peptide to initiate immune checkpoint blockade therapy, thereby enhancing response rates to pancreatic cancer immunotherapy.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03114"},"PeriodicalIF":9.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Co-Delivery Evodiamine-Porphyrin Nano-Drug to Enhance Photodynamic-Chemo-Immunotherapy for Triple-Negative Breast Cancer Treatment.","authors":"Qiang Zhou, Kui Wang, Dahong Yang, Yue Huang, Mengjun Yu, Dandan Xie, Jia Wang, Shiwen Chen, Jing Gong, Min Yang, Yu Zhao, Jingbin Huang","doi":"10.1002/adhm.202503039","DOIUrl":"https://doi.org/10.1002/adhm.202503039","url":null,"abstract":"<p><p>Immunotherapy is a promising treatment for triple-negative breast cancer (TNBC), but the immunosuppressive tumor microenvironment (TME) compromises its efficacy. Therefore, the nano-drug TPGS@EVO/Ppa (TEP) is designed and prepared to achieve chemotherapy and enhance immunotherapy. Evodiamine (EVO) demonstrates chemotherapeutic efficacy and enhanced CD8<sup>+</sup> T cell infiltration within the TME. Additionally, laser irradiation of Pyropheophorbide-a (Ppa) generates singlet oxygen, promoting tumor cell apoptosis and inducing immunogenic cell death (ICD). In vitro and in vivo experiments demonstrate that TEP exhibits significant cytotoxicity against 4T1 tumor cells and markedly inhibits tumor growth. Furthermore, TEP promotes the release of damage-associated molecular patterns (DAMPs) such as calreticulin (CRT), high mobility group box 1 protein (HMGB1), and adenosine triphosphate (ATP), which stimulates dendritic cells (DCs) maturation and activate adaptive immunity. Bilateral tumor experiments reveal that the combination therapy significantly increases the proportions of CD4<sup>+</sup> and CD8<sup>+</sup> T cells in tumors and central memory T cells (TCMs) in the spleen, demonstrating potent immunotherapy efficacy. In summary, TEP emerges as an innovative nano-drug with exceptional anti-tumor properties, offering a novel strategy for the treatment of TNBC.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03039"},"PeriodicalIF":9.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emily B Roloson, Wei-Hung Jung, Stephanie L McNamara, Catherine L Van Stone, Nuria Lafuente-Gómez, Duncan M Morgan, Georg N Duda, David J Mooney
{"title":"Collagen Scaffold Viscoelasticity Regulates Muscle Cell Phenotype.","authors":"Emily B Roloson, Wei-Hung Jung, Stephanie L McNamara, Catherine L Van Stone, Nuria Lafuente-Gómez, Duncan M Morgan, Georg N Duda, David J Mooney","doi":"10.1002/adhm.202502775","DOIUrl":"https://doi.org/10.1002/adhm.202502775","url":null,"abstract":"<p><p>Current biomaterial strategies are typically unable to return skeletal muscle to pre-injury function following damage, resulting in permanent loss of muscle function. Recently, there has been a growing appreciation for the role of matrix viscoelasticity in regenerative processes, and here we address the hypothesis that changes in matrix viscoelasticity regulate muscle cell function. Using norbornene-modified type I collagen hydrogels with a tetrazine-based crosslinker, it is found that myoblast spreading, proliferation, and differentiation are improved on and within slow-relaxing hydrogels. However, satellite cell stemness is maintained only with soft, fast-relaxing hydrogels. This indicates that there is a direct link between the viscoelasticity of collagen-based substrates and muscle cell phenotype in vitro. Together, these studies further the understanding of the role of tissue mechanical properties in directing muscle cell function and provide a tool for guiding specific behaviors necessary for muscle regeneration.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e02775"},"PeriodicalIF":9.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engineering Bacteria in Hydrogel for Photo-Triggered Metabolic-Regulation AND-Gated Tumor Immunotherapy.","authors":"Qiliner Feng, Chen Wang, Si Shi, Junyu Fan, Yurong Chen, Tuanjie Zhang, Zhijun Ruan, Yongzheng Ma, Zifu Li, Jie Liu, Baizhu Chen","doi":"10.1002/adhm.202503275","DOIUrl":"https://doi.org/10.1002/adhm.202503275","url":null,"abstract":"<p><p>Tumor cells reprogram the energy metabolism and re-shape the microenvironment to maintain their fast proliferation and metastasis, leading to immunosuppression. Inspired by the design of engineered living materials, in this study, the AND-gated living hydrogel for metabolic-regulation enhanced tumor immunotherapy is constructed. Bacteria are genetically rewired to express lactate oxidase or glucose oxidase as two inputs under the control of thermosensitive promoter and then encapsulated inside the NIR-light controlled hydrogel. Triggered by laser, the engineered living hydrogel weakened the glycolysis and improved the mitochondrial respiration of tumor cells. The regulation of energy metabolism potentiated the antitumor immune responses by stimulating T cells, polarizing tumor associated macrophages to M1 phenotype, inducing the immunogenic cell death and stimulating the cGAS/STING pathway. With \"high\" inputs of two enzymes, the engineered living hydrogel realized the enhanced tumor immunotherapy as the \"high\" output. An approach of living hydrogel for metabolic-regulation AND-gated tumor immunotherapy is established.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e03275"},"PeriodicalIF":9.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Madhukrishnan Murali, Vishnu Priya Murali, Roopasree O Jayarajan, Abeesh P, Daisy R Sherin, Jayadev S Arya, M M Vishnu Prasad, Elambalassery G Jayasree, Lekha K Nair, Sreejith P Panicker, Kaustabh Kumar Maiti
{"title":"Repurposing Nano-Dimensions of a Small Phytomolecule, Rhein, Into Nano-Rhein to Unveil Its Efficacy on Hypercalciuria-Induced Nephropathies on a SERS-Based Calcification Profiling Platform.","authors":"Madhukrishnan Murali, Vishnu Priya Murali, Roopasree O Jayarajan, Abeesh P, Daisy R Sherin, Jayadev S Arya, M M Vishnu Prasad, Elambalassery G Jayasree, Lekha K Nair, Sreejith P Panicker, Kaustabh Kumar Maiti","doi":"10.1002/adhm.202504133","DOIUrl":"https://doi.org/10.1002/adhm.202504133","url":null,"abstract":"<p><p>Renal disorders induced by calcium oxalate (CaOx) crystals potentiate a complex pathophysiological landscape devoid of effective pharmacological interventions. Herein, a bioactive herbal compound, rhein, isolated from Cassia fistula Linn is known for its well-documented anti-inflammatory and anti-cancer properties. It's role as a CaOx inhibitor has received inadequate scrutiny. The clinical viability of rhein is hampered bypoor aqueous solubility and low bioavailability. To surmount these challenges, a simple and rapid sonochemical self-assembly technique is engineered to transform rhein into nano-rhein, aiming to augment its inhibitory efficacy toward CaOx. The anti-calcification properties of both rhein and nano-rhein were assessed through an in vitro model employing human embryonic kidney cells HEK-293. Through surface-enhanced Raman scattering (SERS), we established a Raman imaging platform to monitor calcification processes. To deepen the understanding of cellular responses to CaOx we conducted an RNA sequencing experiment to evaluate the the transcriptomic modification exerted by nano-rhein. In addition, in vivo studies further demonstrated that nano-rhein significantly reduced renal CaOx crystal deposition and alleviated kidney injury and dysfunction in a C57BL/6 mouse model. This exploration offers intricate insights into the potential of rhein, particularly in its nano form, as a promising therapeutic agent for CaOx-induced nephropathies.</p>","PeriodicalId":113,"journal":{"name":"Advanced Healthcare Materials","volume":" ","pages":"e04133"},"PeriodicalIF":9.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}