{"title":"Hierarchically Reinforced Gelatin/Phytic Acid Composite Sponges with Electrostatic Affinity for Long-Term Sustained Release of Cationic Drugs.","authors":"Beizhe Huang, Ting Zhang, Jun Chen, Ranjith Kumar Kankala, Ai-Zheng Chen, Jianting Zhang","doi":"10.1021/acsabm.6c01546","DOIUrl":"https://doi.org/10.1021/acsabm.6c01546","url":null,"abstract":"<p><p>Natural polymer-based sustained-release drug delivery systems are often hampered by insufficient structural stability and weak intermolecular affinities between the drug and the polymeric matrix. To overcome these limitations, herein, we engineered a covalently/non-covalently crosslinked porous gelatin sponge using a chemical crosslinker and polyanionic phytic acid (PA). PA reinforced the gelatin backbone and provided abundant electronegative phosphate groups as drug-anchoring sites, creating a high-affinity microenvironment. Using differently charged model drugs, the sponges exhibited prolonged release, with the release kinetics fitting the Higuchi model. Notably, in vitro release of cationic drugs extended beyond 200 h. These results translated into in vivo therapeutic efficacy, as validated in local anesthesia models using bupivacaine and wound repair models with polyhexamethylene biguanide. In summary, this designed porous framework offers a promising paradigm for fabricating natural polymer-based sustained-release drug delivery systems.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valerie Muya, Aayushi Vyas, Nishaka William, Jason Acker, Marya Ahmed
{"title":"Role of Crosslinker Chemistry and Comonomer Type on Cryopreservation Efficacies of Nanogels.","authors":"Valerie Muya, Aayushi Vyas, Nishaka William, Jason Acker, Marya Ahmed","doi":"10.1021/acsabm.6c01328","DOIUrl":"https://doi.org/10.1021/acsabm.6c01328","url":null,"abstract":"<p><p>Nonpermeating cryoprotective agents (CPAs) represent an alternative to reduce the dependence on small molecules such as dimethyl sulfoxide and glycerol that may cause toxic effects in sensitive cell lines. In this work, a library of lactone-modified poly(vitamin B5 analogous monomer (B5AMA))-based nanogels with systematically tuned amphipathicity and crosslinker chemistry were synthesized and evaluated as extracellular CPAs for the cryopreservation of human red blood cells and murine breast cancer cells. Three γ-hydroxy(amino)amide methacrylamide comonomers possessing variable alkyl chain lengths were prepared and incorporated into poly(B5AMA) nanogel networks utilizing three structurally distinct bifunctional crosslinkers. Nanogels were characterized by dynamic light scattering, zeta potential, and transmission electron microscopy, demonstrating sub-100 nm dimensions and a porous structure. The nanogel formulations prepared with different crosslinkers and comonomers possessed different volume phase transition temperatures and hence overall amphipathicity and demonstrated enhanced IRI activities relative to hydrophilic analogues. The nanogel synthesized with different crosslinkers clearly demonstrated the role of crosslinker amphipathicity in the cryopreservation efficacies of mammalian cells. Meanwhile, amphipathic formulations prepared by copolymerizing B5AMA with γ-hydroxy(amino)amide methacrylamide comonomers in the presence of a specific crosslinker demonstrated crosslinker- and comonomer-type-dependent cryopreservation efficacies in different cell types. Collectively, these findings demonstrate that amphipathicity, crosslinker chemistry, polymer network architecture, and macromolecular crowding jointly govern cryoprotective outcomes, positioning lactone-modified poly(B5AMA) nanogels as promising macromolecular CPAs for use in the preservation of cell-based therapies.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Asymmetric Heptamethine Cyanine: A Phototheranostic Agent for Primary Liver Cancer Treatments.","authors":"Charupong Saengboonmee, Pitchaya Amornkittithaworn, Onnicha Khaikate, Prapassara Muangsopa, Pornthip Piyanuch, Padcharee Yueangchantuek, Kanyarat Thithuan, Cheerapinya Taebprakhon, Seiji Okada, Kantapat Chansaenpak, Mongkol Sukwattanasinitt, Anyanee Kamkaew","doi":"10.1021/acsabm.6c01466","DOIUrl":"https://doi.org/10.1021/acsabm.6c01466","url":null,"abstract":"<p><p>Abnormal pH and viscosity are defining features of the tumor microenvironment, offering valuable targets for cancer diagnostics and therapy. Here, we introduce Cy7-TCF-Mpip, a triple-functional near-infrared (NIR) probe that integrates pH responsiveness, viscosity sensitivity, and photodynamic activity within a single heptamethine cyanine scaffold. Cy7-TCF-Mpip exhibits substantial fluorescence enhancement under acidic and high-viscosity conditions, as well as NIR absorption/emission (724-870 nm), and efficient singlet oxygen generation (ΦΔ up to 0.065) upon 660 nm irradiation. The probe selectively accumulates in hepatocellular carcinoma and cholangiocarcinoma (CCA) cells, responding dynamically to changes in hypoxia-induced acidity and cellular viscosity. Upon light activation, Cy7-TCF-Mpip induces potent, ROS-mediated photodynamic cytotoxicity with minimal dark toxicity and preferential phototoxicity toward CCA cells compared with nonmalignant cholangiocytes under the tested conditions. In vivo, the probe significantly suppresses tumor growth in a CCA xenograft model after local 660 nm light irradiation, with no observable body-weight loss or obvious behavioral abnormalities under the tested conditions. Overall, Cy7-TCF-Mpip represents a compact and versatile NIR theranostic platform for image-guided photodynamic therapy of primary liver cancers.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149316069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Simulation-Driven Optimization of Nanocomposite Auxetic Intervertebral Disc Substitutes Mimicking Native Mechanics","authors":"Sumit Suryakant Kolte, Vinayak Vijayan, Lihua Lou","doi":"10.1021/acsabm.6c00702","DOIUrl":"10.1021/acsabm.6c00702","url":null,"abstract":"<p>Intervertebral disc degeneration remains a leading cause of chronic low back pain, and current disc replacement designs often fail to reproduce the behavior of the native intervertebral disc. This study evaluated chiral auxetic disc replacements incorporating polymeric and nanocomposite cores and compared them with a native L4–L5 disc model and a representative commercial implant. The finite element model included cancellous vertebral cores with cortical shells and was subjected to 2.8 mm axial compression and 7.5 N·m pure moments in flexion, extension, and lateral bending. Interfacial pressure, tangential contact stress, and sliding distance were evaluated under compression using pointwise agreement mapping, while posterior anterior–posterior displacement and strain energy were evaluated across all loading modes. The ultra-high molecular-weight polyethylene (UHMWPE) auxetic design provided the strongest overall performance among the proposed designs, with 31.25% pressure agreement and 49.33% sliding-distance agreement with the native disc, compared with 1.01% and 11.47%, respectively, for the commercial design. Graphene-reinforced UHMWPE produced the highest tangential contact stress agreement (34.06%) but reduced pressure and sliding-distance agreement relative to UHMWPE. UHMWPE also provided the closest strain energy response among the auxetic designs and closely reproduced the native posterior displacement during flexion. However, its range of motion remained substantially lower than the native disc, revealing a tradeoff between favorable compressive behavior and rotational compliance. These findings identify the UHMWPE chiral architecture as the most promising design evaluated while demonstrating the need for further geometric optimization to reduce bending stiffness.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 21","pages":"10116–10128"},"PeriodicalIF":5.6,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sonali Gupta, Mansi Murkar, Bijaideep Dutta, S. B. Shelar, K. C. Barick
{"title":"Tailoring the Surface of Ag2S Nanoparticles for Targeted, Light-Triggered Eradication of Cancer Cells","authors":"Sonali Gupta, Mansi Murkar, Bijaideep Dutta, S. B. Shelar, K. C. Barick","doi":"10.1021/acsabm.6c01709","DOIUrl":"10.1021/acsabm.6c01709","url":null,"abstract":"<p>Nanostructure-mediated targeted photothermal therapy (PTT) emerged as a minimally invasive frontier in precision oncology, offering the ability to ablate malignancies. The tailoring of the surface of nanostructures serves as the ultimate bridge between material design and targeted PTT. In this aspect, the surface of Ag<sub>2</sub>S nanoparticles (Ag<sub>2</sub>S NPs) was engineered with hydrophilic, organic architectures to achieve superior colloidal stability and selective cellular uptake, ultimately enabling light-triggered eradication of cancer cells. The successful formation of the monoclinic Ag<sub>2</sub>S phase was confirmed by XRD and TEM analyses, and its surface modification with cysteine was evident from FTIR and light scattering measurements. The developed water-dispersible and biocompatible cysteine-functionalized Ag<sub>2</sub>S NPs (Cy-Ag<sub>2</sub>S NPs) showed sufficient absorbance in near-infrared (NIR) region and also exhibited good photothermal heating efficacy under 808 nm laser light. In order to achieve site-selective targeting toward cancer cells, folic acid (FA) was introduced onto the surface of Cy-Ag<sub>2</sub>S NPs via EDC-NHS coupling. In vitro studies showed negligible cytotoxicity of FA-conjugated Cy-Ag<sub>2</sub>S NPs (FA@Cy-Ag<sub>2</sub>S NPs) under dark conditions, whereas pronounced cancer cell ablation was observed under NIR irradiation. Moreover, the FA@Cy-Ag<sub>2</sub>S NPs showed targeted behavior toward folate receptor (FR)-positive KB cells over FR-negative A549 cells through apoptotic induction, suggesting their potential application in targeted PTT.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 21","pages":"10497–10508"},"PeriodicalIF":5.6,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nurdiana Nordin, M. Arman Shaharulnizam, Marlin Alya Zamlis, Nurfarhanim Abu Bakar
{"title":"Crosslinking-Dependent Structure–Transport–Function Relationships in Gelatin–Hyaluronic Acid Hydrogels for Wound-Fluid Management","authors":"Nurdiana Nordin, M. Arman Shaharulnizam, Marlin Alya Zamlis, Nurfarhanim Abu Bakar","doi":"10.1021/acsabm.6c01693","DOIUrl":"10.1021/acsabm.6c01693","url":null,"abstract":"<p>Effective wound-fluid management is essential in medical applications, as dressings must absorb, retain, and regulate excess blood, exudate, and other biological fluids. Gelatin–hyaluronic acid (Gel/HA) hydrogels are promising dressing materials because they provide a hydrated, tissue-mimetic environment and combine the biological functions of both polymers. Their performance depends strongly on the crosslinking strategy, which regulates network architecture, fluid transport, and mechanical integrity. Three Gel/HA networks were prepared by physical association (Network I), glutaraldehyde-mediated covalent crosslinking (Network II), and PEGDA-mediated interpenetrating-network formation (Network III). Molecular interactions, morphology, fluid uptake, and mechanical properties were evaluated within a structure–transport–function framework. The networks exhibited distinct pore structures, with average pore sizes of 21 ± 7, 2.3 ± 0.8, and 9 ± 3 μm and porosities of 74 ± 3, 59 ± 3, and 67 ± 3% for Networks I–III, respectively. Tensile strength increased from 62 ± 5 kPa for Network I to 127 ± 7 kPa for Network II and 215 ± 9 kPa for Network III, while elongation at break increased from 152 ± 9 to 257 ± 12 and 343 ± 14%, respectively. Simulated blood uptake at 240 min reached 483 ± 45, 842 ± 59, and 1285 ± 72% for Networks I–III, respectively. An integrated hydrogel performance index was used as a comparative dimensionless descriptor of selected transport and mechanical properties. Overall, the results show that network formulation yields distinct combinations of pore architecture, fluid transport, and mechanical performance, providing a basis for comparing Gel/HA hydrogel designs for wound management applications that balance fluid management and mechanical properties.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 21","pages":"10465–10478"},"PeriodicalIF":5.6,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Review on MXene and MXene-Based Composites for Advanced Biosensing and Bioimaging: Progress, Challenges, and Future Perspectives","authors":"Shweta, Rajat Kumar Mishra, Rakhi, Akhileshwar Gupta, Vivek Masih, Chandki Ram Gautam","doi":"10.1021/acsabm.6c01358","DOIUrl":"10.1021/acsabm.6c01358","url":null,"abstract":"<p>Recently, the growth of two-dimensional (2D) materials has opened innovative paths in nanobiotechnology, and MXenes have emerged as leading candidates owing to their superior physicochemical performance and functional adaptability. MXenes, a family of transition metal carbides, nitrides, and carbonitrides, reveal excellent electrical conductivity, large surface area, tuneable surface chemistry, hydrophilicity, and exceptional biocompatibility. These unique features make them highly attractive for biosensing and bioimaging applications. This review systematically abridges the recent advancements in MXene and its composites for biosensor development, containing electrochemical, optical, wearable, and flexible biosensors for the revealing of biomolecules, pathogens, cancer biomarkers, and glucose. The role of surface functionalization, hybridization with polymers, metal nanoparticles, carbon-based nanomaterials, and biomolecules in enhancing sensitivity, selectivity, and stability is critically deliberated. Moreover, the application of MXene composites in bioimaging approaches such as fluorescence imaging, photoacoustic imaging, magnetic resonance imaging (MRI), and multimodal imaging is explored, emphasizing their photothermal conversion efficiency and contrast development competences. Various challenges associated with long-term stability, oxidation resistance, toxicity, and large-scale production were also addressed, along with future perspectives for clinical translation and next-generation smart biomedical platforms. Overall, MXene-based materials clamp significant potential to transform biosensing and bioimaging techniques via multifunctional and integrated diagnostic systems.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 21","pages":"9983–10025"},"PeriodicalIF":5.6,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Engineered Chitosan Nanoparticle Platform Enables Controlled Ibuprofen Delivery and Coordinated Neuroimmune Regulation in a Human Microphysiological Model","authors":"Nandita Menon, Anil Kishen","doi":"10.1021/acsabm.6c01383","DOIUrl":"10.1021/acsabm.6c01383","url":null,"abstract":"<p>Controlled delivery of anti-inflammatory agents using bioactive nanomaterials offers a strategy to achieve localized and temporally regulated modulation of inflammatory and neurogenic signaling. Here, we engineered an adsorption-based chitosan nanoparticle platform for controlled Ibuprofen delivery to coordinate inflammatory and neurogenic responses during the acute postoperative phase. The formulation was designed to generate an initial burst release followed by sustained drug delivery while leveraging the intrinsic immunomodulatory properties of chitosan. Therapeutic performance was evaluated using a previously established human three-dimensional tri-culture microfluidic platform (3TMP) that recreates the periodontal ligament neuroimmune microenvironment under lipopolysaccharide (LPS)-induced inflammatory conditions. The engineered platform exhibited a two-phase release profile characterized by an initial burst followed by a plateau that translated into coordinated suppression of interconnected inflammatory and neuronal pathways, including the reduction of pro-inflammatory cytokines, prostaglandin E2 (PGE2), calcitonin gene-related peptide (CGRP), and the nociceptive ion channels TRPV1 and TRPA1. In comparison, free Ibuprofen only partially reduced TNF-α, IL-6, and IL-8 and failed to suppress IL-1β, PGE2, TRPV1, or TRPA1. These findings demonstrate how controlled-release biomaterial design governs therapeutic performance by coordinating interconnected neuroimmune pathways. Furthermore, this work establishes human microphysiological systems as robust platforms for evaluating structure–function relationships in bioactive nanotherapeutic systems for periodontal inflammation.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 21","pages":"10264–10276"},"PeriodicalIF":5.6,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149214785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nanomaterial Design for Macrophage Reprogramming: Emerging Strategies and Mechanistic Insights for Inflammation and Tumor Therapy","authors":"Nitish Giri, Atanu Chakraborty","doi":"10.1021/acsabm.6c01937","DOIUrl":"10.1021/acsabm.6c01937","url":null,"abstract":"<p>Macrophages play a paradoxical role in inflammation and tumor. They can protect the host during acute inflammation but act as the main driver for the chronic inflammation which is a common characteristic of several diseases including rheumatoid arthritis, atherosclerosis, type 2 diabetes, inflammatory bowel disease, and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In the tumor microenvironment, macrophages switch their phenotype to the immunosuppressive M2 state that promotes tumor growth, angiogenesis, and metastasis. Emerging nanomaterial platforms are trying to offer transformative solutions by enabling the precise delivery of immunomodulatory drugs directly to disease-site macrophages.</p><p>This review will provide comprehensive comparative analysis of these emerging nanomaterial designs strategies across two disease paradigms: inflammatory diseases and tumor. The discussion will focus on various strategies which include inhibiting chemokine axis (CCL2-CCR2 axis), selective elimination of macrophages through apoptosis, metabolic reprogramming, biomimetic and apoptotic cell-inspired nanoparticles leveraging natural macrophage clearance pathways to promote M2 polarization in inflammation, and the activation of tumor-associated macrophages via TLR and STING agonist. We highlight the role of nanoparticle surface chemistry, composition, and targeting ligands in achieving the two opposite therapeutic outcomes of these two diseases while maintaining some common design principles including EPR-mediated accumulation at the disease sites and biomimetic modifications. We also mentioned novel next-generation nanoparticle-based platforms that are currently in clinical trials for the treatment of tumor and inflammatory diseases. Finally, we discuss the barriers that limit the clinical translational potential of broad nanoparticles, with particular emphasis on nanoparticle-related immunotoxicity, macrophage heterogeneity, and manufacturing reproducibility of the nanoparticles.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 21","pages":"10063–10089"},"PeriodicalIF":5.6,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Minji Ko, Heejin Jung, Kayoung Shin, Sungwoo Kim, Keyong Nam Lee, Young Kwang Lee, Sekyoo Jeong, Young Rag Do
{"title":"EPOTF-Enabled Scalable Production of Structurally Intact Lemon-Derived Extracellular Vesicles with Enhanced Bioactivity","authors":"Minji Ko, Heejin Jung, Kayoung Shin, Sungwoo Kim, Keyong Nam Lee, Young Kwang Lee, Sekyoo Jeong, Young Rag Do","doi":"10.1021/acsabm.6c01073","DOIUrl":"10.1021/acsabm.6c01073","url":null,"abstract":"<p>Lemon-derived extracellular vesicles (LDEVs) have attracted increasing attention as promising bioactive nanovesicles for cosmetic and skin engineering applications owing to their biocompatibility, bioactive cargo, and skin-friendly lipid bilayer structure. However, the lack of standardized purification methods and limited scalability remain critical bottlenecks for the practical application and industrial translation of LDEVs. In this study, we developed an electrophoretic oscillation-assisted tangential flow filtration (EPOTF) platform using a SiN<sub><em>x</em></sub> membrane nanofilter for the scalable and high-purity purification of structurally intact LDEVs. The EPOTF process effectively suppressed membrane cake formation and membrane fouling, enabling stable size-selective purification under large-volume conditions. EPOTF-purified LDEVs exhibited stable physicochemical characteristics, high recovery yield, and excellent batch-to-batch reproducibility. Cryo-TEM analysis confirmed preservation of a distinct lipid bilayer structure and near-ideal spherical morphology with low spherical deviation, indicating minimal structural damage during purification. Furthermore, EPOTF-purified LDEVs significantly enhanced hydration, antioxidant activity, skin barrier recovery, and anti-inflammatory responses in an ex vivo human skin explant model. Taken together, these findings establish EPOTF as a robust and scalable purification platform for the biomanufacturing of high-quality LDEVs, with strong potential for cosmetic and skin-engineering applications.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 21","pages":"10220–10231"},"PeriodicalIF":5.6,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}