Smart Materials in Medicine最新文献

{"title":"Chiral noble-metal nanomaterials: Chiral origins and biomedical applications","authors":"Binqian Zhou ,&nbsp;Yunxiang Zhang ,&nbsp;Qian Lei ,&nbsp;Zhitao Zhang ,&nbsp;Rui Wang ,&nbsp;Peizhao Liu ,&nbsp;Xiaoqian Xu ,&nbsp;Tingting Jia ,&nbsp;Jiaji Cheng","doi":"10.1016/j.smaim.2026.01.001","DOIUrl":"10.1016/j.smaim.2026.01.001","url":null,"abstract":"<div><div>Chirality is a fundamental property in nature, and the rapid progress of nanoscience has enabled the design and fabrication of nanoscale materials with precisely controlled chiral architectures. These chiral nanostructures exhibit unique optical, catalytic, and sensing characteristics. Among them, chiral noble-metal nanomaterials owing to their intrinsic localized surface plasmon resonance, catalytic activity, and biocompatibility, show tremendous application potential in the biomedical field. This review provides a comprehensive overview of chiral noble-metal nanomaterials. We first summarize their chiroptical properties and discuss the structural origins of chirality at the molecular, nanoscale, and nano-/micro-size. We then highlight biomedical applications, including biosensing, enantioselective separation, antibacterial applications, neurodegenerative diseases and cancer diagnosis and therapy. Finally, we discuss the key challenges that must be addressed, including the precise and reproducible fabrication of chiral nanostructures, unresolved biosafety concerns, and an incomplete mechanistic understanding at the molecular and cellular levels. We anticipate that, by overcoming these challenges, chiral noble-metal nanomaterials will assume increasingly impactful roles in biomedicine.</div></div>","PeriodicalId":22019,"journal":{"name":"Smart Materials in Medicine","volume":"7 ","pages":"Pages 59-76"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173658","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":"Smart DNA nanocages mitigate oxidative stress and guide bone immune microenvironment for osteoporotic jawbone regeneration","authors":"Shebin Hong ,&nbsp;Ya Cui ,&nbsp;Weidong Jiang ,&nbsp;Hao Wu ,&nbsp;Cancan Zhao ,&nbsp;Weihong Xi ,&nbsp;Xudong Wang","doi":"10.1016/j.smaim.2025.12.002","DOIUrl":"10.1016/j.smaim.2025.12.002","url":null,"abstract":"<div><div>Jawbone regeneration in osteoporotic patients remains a formidable challenge due to excessive reactive oxygen species (ROS), dysregulated bone immunity, and compromised osteogenic capacity. While nanomaterial-based modulation of the bone microenvironment has emerged as a promising therapeutic strategy, most current biomaterial-based approaches target only one or two aspects of this multifaceted pathology. In this study, we developed tetrahedral DNA nanocages (TDN), which exhibit notable advantages including high biocompatibility, efficient cellular internalization, and multifaceted bioactivities that concurrently address key pathological processes in osteoporotic bone defects. Our findings demonstrate that TDN effectively scavenges intracellular ROS induced by LPS, restores mitochondrial membrane potential, and attenuates oxidative stress. Additionally, TDN promotes macrophage polarization toward the M2 phenotype and suppresses the release of pro-inflammatory cytokines by inhibiting the TNF-α/NF-κB pathway, thereby modulating immune balance. Furthermore, TDN was shown to promote the proliferation, migration, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells from osteoporotic rats (OVX-BMSCs), while inhibiting their adipogenic differentiation. In vivo experiments demonstrated that TDN delivered via gelatin methacryloyl (GelMA) hydrogel scaffolds significantly enhanced regeneration in critical-sized mandibular defects in an osteoporotic model. In summary, this study reveals the multifaceted functions of TDN in alleviating oxidative stress, modulating immune homeostasis, and promoting osteogenesis within the challenging osteoporotic microenvironment, thereby offering a promising and translatable strategy for craniofacial bone regeneration in osteoporosis.</div></div>","PeriodicalId":22019,"journal":{"name":"Smart Materials in Medicine","volume":"7 ","pages":"Pages 44-58"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173659","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 dynamic hydrogel platform enables localized delivery of microRNAs and osteogenic growth peptide for the treatment of osteosarcoma","authors":"Jie Cang ,&nbsp;Wenbo He ,&nbsp;Feipeng Wu ,&nbsp;Ruixing Shui ,&nbsp;Xianwen Yan ,&nbsp;Miao Wang ,&nbsp;Xu Chen ,&nbsp;Junmeng Liu ,&nbsp;Dapeng Li ,&nbsp;Zhenhuan Jiang ,&nbsp;Guoqing Pan","doi":"10.1016/j.smaim.2026.03.001","DOIUrl":"10.1016/j.smaim.2026.03.001","url":null,"abstract":"<div><div>The clinical management of osteosarcoma remains a major therapeutic challenge, mainly owing to the high risk of tumor recurrence driven by residual cancer cells after surgical resection and the persistent difficulty in reconstructing irregular bone defects. To address these challenges, we engineered a Schiff base crosslinked, injectable, and dynamically responsive hydrogel platform composed of polyethyleneimine (PEI) and oxidized hyaluronic acid (OHA), with OHA serving as a structural backbone. We functionalized with osteogenic growth peptide (OGP) and small noncoding RNA (miR-143). Upon injection, the platform undergoes rapid in situ gelation, enabling precise localization at the tumor resection site and pH-responsive degradation-mediated sequential release of therapeutic agents. In vivo studies confirmed that the OHA-PEI-OGP/miR-143 hydrogel significantly inhibits osteosarcoma recurrence through sustained and localized delivery of miR-143 and OGP, thereby enhancing treatment efficacy while minimizing off-target effects. This localized delivery platform could possibly lessen the needed therapeutic dose and dosing frequency compared to regular systemic administration, reducing the danger of widespread off-target toxicity. Extensive in vitro and in vivo evaluations have illustrated that it not only significantly enhances bone regeneration but also effectively shifts the postoperative inflammatory environment towards an anti-inflammatory and regenerative condition. Together, these observations underscore its dual-function ability, particularly OHA-PEI-OGP/miR-143, in both preventing tumor return and aiding in bone repair, thereby presenting itself as an up-and-coming option for clinical use in intricate postoperative treatment of osteosarcoma.</div></div>","PeriodicalId":22019,"journal":{"name":"Smart Materials in Medicine","volume":"7 ","pages":"Pages 116-131"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147538572","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":"Macrophage membrane-camouflaged nanoparticles as emerging therapeutics in metabolic dysfunction-associated steatotic liver disease","authors":"Nattadon Ariyathanapong ,&nbsp;Kanyapat Ploypradith ,&nbsp;Papawarin Kisara Yoshimura ,&nbsp;Chitinart Thedrattanawong ,&nbsp;Torsten Wuestefeld ,&nbsp;Asada Leelahavanichkul ,&nbsp;Tianle Jin ,&nbsp;Lanyin Mao ,&nbsp;Ronnie H. Fang ,&nbsp;Yong-An Lee ,&nbsp;Soracha D. Thamphiwatana","doi":"10.1016/j.smaim.2026.02.001","DOIUrl":"10.1016/j.smaim.2026.02.001","url":null,"abstract":"<div><div>Chronic liver disease (CLD) is a major global health burden, with metabolic dysfunction-associated steatotic liver disease (MASLD) as a primary contributor through its promotion of persistent inflammation, fibrotic transformations, and increased cancer risk. Current therapeutic strategies remain inadequate due to poor pharmacokinetics and off-target toxicity, underscoring the need for more targeted and safer treatment options. Macrophages, as key components of the innate immune system, play a central role in liver homeostasis and inflammation, critically shape disease progression and thus represent a compelling therapeutic target. Advances in nanomedicine have led to the development of macrophage membrane–camouflaged nanoparticles (MMNPs), which offer immune-evasive and inflammation-targeting properties conferred by the macrophage membrane. Given the major involvement of macrophages throughout the course of CLD and the superior immunomodulatory properties of their membrane, MMNPs provide a promising and innovative strategy for CLD therapy. This review provides a comprehensive overview of MASLD-associated CLD pathology with a particular focus on the role of macrophages in disease progression. It further explores the characteristics, function-ality, and liver-targeting modifications of MMNPs, highlighting their potential in modulating key pathways to remodel inflammatory environment and reverse liver fibrosis. Finally, existing challenges and future prospects of MMNP-based therapies are discussed, including strategies for enhancing therapeutic efficacy through combination approaches and bioengineering advancements.</div></div>","PeriodicalId":22019,"journal":{"name":"Smart Materials in Medicine","volume":"7 ","pages":"Pages 77-92"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147397679","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":"Advanced nanomaterials for myocardial ischemia-reperfusion injury: Bridging precision imaging to targeted therapy","authors":"Jie Li ,&nbsp;Muhammad Shafiq ,&nbsp;Minghua Yao ,&nbsp;Zehua Liu ,&nbsp;Ruizhi Tian ,&nbsp;Fangqiao Zheng ,&nbsp;Chan Lu ,&nbsp;Ming Ma","doi":"10.1016/j.smaim.2025.12.003","DOIUrl":"10.1016/j.smaim.2025.12.003","url":null,"abstract":"<div><div>Myocardial ischemia-reperfusion injury (MIRI) is a major cause of heart failure, driven by oxidative stress, inflammation, and rapid loss of cardiomyocytes. Traditional therapies for MIRI remain limited, largely due to poor cardiac targeting and an absence of real-time diagnostic capabilities. Recently, various nanomaterials (NMs) have been extensively developed and applied to achieve more precise and effective treatment of MIRI, owing to their favorable biosafety and functional tunability. This review comprehensively summarizes the latest research progress on functional NMs in diagnostic imaging and therapeutic interventions for MIRI. In the context of diagnostic imaging, <em>in vitro</em> nano-biosensors enable the early detection of MIRI biomarkers, while NM-enhanced imaging modalities provide high diagnostic precision at the <em>in vivo</em> level and support real-time therapeutic guidance. Therapeutically, NMs can be leveraged as direct antioxidative agents, vehicles for targeted gene therapy, and platforms for combination regimens including gas therapy, stem cell therapy, and circadian rhythm modulation, to enhance myocardial repair. By synthesizing these advancements, this review provides conceptual and technological insights that could guide the future of nanomedicine-enabled precision cardiovascular care.</div></div>","PeriodicalId":22019,"journal":{"name":"Smart Materials in Medicine","volume":"7 ","pages":"Pages 13-43"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023355","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":"Integrating siRNA targeting PKM2 with photodynamic therapy to induce tumor energy collapse","authors":"Rourou Miao ,&nbsp;Ran Luo ,&nbsp;Jiahui Cao ,&nbsp;Wen Li ,&nbsp;Yiqiu Fu ,&nbsp;Xinyi Wang ,&nbsp;Wen Zhang ,&nbsp;Liu Yu ,&nbsp;Meitong Ou ,&nbsp;Lin Mei","doi":"10.1016/j.smaim.2026.04.001","DOIUrl":"10.1016/j.smaim.2026.04.001","url":null,"abstract":"<div><div>Tumor cells exhibit an exceptionally high demand for energy to sustain uncontrolled proliferation and predominantly rely on glycolysis, rendering them vulnerable to energy-targeting interventions. However, metabolic plasticity often enables adaptive compensation, thereby limiting the efficacy of conventional metabolic starvation strategies. Herein, we present a synergistic therapeutic strategy that integrates siRNA targeting pyruvate kinase M2 (PKM2) with photodynamic therapy (PDT) to induce tumor energy collapse. A cationic polymer–chlorin e6 (Ce6) nanocomplex was constructed by conjugating Ce6 to fourth-generation polyamidoamine (PAMAM), enabling efficient encapsulation and intracellular delivery of PKM2-specific siRNA (siPKM2/CPN). siRNA targeting PKM2 effectively suppressed glycolytic flux, reduced ATP production, and impaired mitochondrial oxidative phosphorylation, thereby inducing severe energy deprivation in tumor cells. Notably, PKM2 knockdown sensitized tumor cells to PDT by amplifying reactive oxygen species generation and exacerbating mitochondrial dysfunction. Mechanistically, the combined treatment activated the mitochondrial apoptotic pathway, as evidenced by increased mitochondrial membrane permeabilization, cytochrome <em>c</em> (Cyt <em>c</em>) release, and caspase-3 activation, ultimately leading to enhanced tumor cell apoptosis. This dual-targeting strategy effectively overcomes tumor metabolic adaptability and highlights metabolic modulation as a promising approach for the next-generation combination cancer therapy.</div></div>","PeriodicalId":22019,"journal":{"name":"Smart Materials in Medicine","volume":"7 ","pages":"Pages 132-143"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147702866","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":"Transduction strategies in enzyme-free nanomaterial-based aptasensors for tetracycline antibiotics: A review","authors":"Minh Duc Luu ,&nbsp;Mai Thi Tran ,&nbsp;Son Hai Nguyen","doi":"10.1016/j.smaim.2026.02.002","DOIUrl":"10.1016/j.smaim.2026.02.002","url":null,"abstract":"<div><div>Enzyme-free aptamer-based biosensors have gained increasing attention for tetracycline monitoring, yet existing studies remain highly fragmented across materials and sensing formats. This review presents a mechanistic framework that systematically classifies optical and electrochemical aptasensors by their transduction pathways rather than by individual nanomaterials. Representative fluorescence, colorimetric, SERS, SPR, chemiluminescence, electrochemical impedance, voltammetric, photoelectrochemical, and electrochemiluminescent systems are critically compared to elucidate how aptamer conformational changes, interfacial interactions, and signal amplification mechanisms govern analytical performance. Beyond reporting detection limits, the review emphasizes real-sample applicability, discussing matrix effects, cross-selectivity among tetracycline analogues, and practical deployment constraints. Comparative analysis with conventional methods highlights biosensors as complementary tools for rapid, decentralized screening rather than direct replacements for laboratory-based quantification. Finally, emerging directions, including microfluidic integration, miniaturized readout systems, and intelligent data processing, are outlined as key strategies toward robust, portable, and field-deployable tetracycline-sensing platforms.</div></div>","PeriodicalId":22019,"journal":{"name":"Smart Materials in Medicine","volume":"7 ","pages":"Pages 93-115"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147397680","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":"Dual-antibacterial nano-sheet synergizes resveratrol delivery for burn regeneration","authors":"Yuzhong Zhang ,&nbsp;Shenglin Geng ,&nbsp;Junxiao Zhang ,&nbsp;Lan Ma ,&nbsp;Jinhe Tian ,&nbsp;Yuanying Guo ,&nbsp;Guojuan Fan ,&nbsp;Weifen Zhang ,&nbsp;Jinlong Ma","doi":"10.1016/j.smaim.2025.12.001","DOIUrl":"10.1016/j.smaim.2025.12.001","url":null,"abstract":"<div><div>In the field of burn treatment, where infected wound sites face critical challenges such as inadequate antimicrobial efficacy and impaired tissue regeneration, developing multifunctional strategies that synergize antibacterial activity and regenerative promotion remains an urgent need. Here, we developed a zinc ion (Zn²⁺) and 2,2′-azobis[2-(2-imidazolin-2-yl)propane] (AIP)-based antibacterial nano-carrier (ZIP) for co-delivering resveratrol (Res) and indocyanine green (ICG) (R/I@ZIP) for burn regeneration. The ZIP platform demonstrates dual intrinsic antibacterial mechanisms through sustained Zn²⁺ release and free radical generation, effectively overcoming resveratrol's inherent antimicrobial limitations. Notably, R/I@ZIP employs thermodynamic therapy mediated by ICG instead of conventional photothermal approaches, eliminating the risks of thermal damage that cause secondary tissue injury. The system exhibits pH-responsive drug release behavior, accelerating resveratrol release in acidic wound environments to synergistically enhance fibroblast proliferation, collagen synthesis, and tissue regeneration. In murine models of infected burn wounds, R/I@ZIP demonstrated superior therapeutic outcomes through combined antimicrobial action and regenerative promotion. This work presents a paradigm-shifting multifunctional platform that integrates intrinsic therapeutic properties with drug delivery capabilities, while overcoming the weak antimicrobial ability of resveratrol in burn management.</div></div>","PeriodicalId":22019,"journal":{"name":"Smart Materials in Medicine","volume":"7 ","pages":"Pages 1-12"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145891196","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":"Recent advances in polymer 4D printing: 3D printing techniques, smart material design, and healthcare applications","authors":"Ziwen Wang,&nbsp;Zebang Zhang,&nbsp;Xiao Kuang","doi":"10.1016/j.smaim.2025.09.001","DOIUrl":"10.1016/j.smaim.2025.09.001","url":null,"abstract":"<div><div>Fourth-dimensional (4D) printing has progressed tremendously since its first conceptualization in 2013. 4D printing is an emerging branch of three-dimensional (3D) printing that allows printed parts to change their shapes and properties as a function of time under external stimuli. It has revolutionized the fabrication of smart polymer composites with customized geometry and programmed dynamic functions for expanding engineering and healthcare applications. This review provides a comprehensive overview of recent advances in the 4D printing of polymer composites, emphasizing three pivotal areas: 3D printing methodologies, smart material design, and their healthcare applications. We start with 3D printing techniques, encompassing traditional methods, multimaterial printing approaches, and other emerging technologies for functional polymer systems. We discuss the molecular engineering of shape-shifting smart polymers, including shape memory polymers, liquid crystal elastomers, magnetoactive soft materials, and hydrogel composites. The structural design strategies and modeling-guided design of smart materials are also covered. We summarize the emerging healthcare applications of 4D-printed polymer composites in medical devices, soft robotics, wearables, drug delivery, and tissue repair/regeneration. Finally, challenges, opportunities, and future directions are highlighted in material design and printing techniques for 4D printing to advance next-generation healthcare solutions.</div></div>","PeriodicalId":22019,"journal":{"name":"Smart Materials in Medicine","volume":"6 3","pages":"Pages 305-333"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108727","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":"EXPECT: A thermosensitive embedded bioprinting platform for guided spatial cell organization","authors":"Athanasia Pylostomou ,&nbsp;Jacek K. Wychowaniec ,&nbsp;Riccardo Tognato ,&nbsp;Sarah T. Egger ,&nbsp;Gion U. Alig ,&nbsp;Charlotte J.C. Edwards-Gayle ,&nbsp;Fatemeh Safari ,&nbsp;Jennifer R. Weiser ,&nbsp;Dagnija Loca ,&nbsp;Matteo D'Este ,&nbsp;Tiziano Serra ,&nbsp;Andrea J. Vernengo","doi":"10.1016/j.smaim.2025.09.002","DOIUrl":"10.1016/j.smaim.2025.09.002","url":null,"abstract":"<div><div>Complex tissue engineering requires precise spatial cell organization, but static or isotropic hydrogels hinder long-term pattern maintenance due to random cell migration. We developed EXtrusion Patterned Embedded ConstruCT (EXPECT), a thermosensitive hydrogel embedding medium for 3D bioprinting, integrating Carbopol® 940 and gelatin for rheological properties and print fidelity, with poly (N-isopropylacrylamide)-graft-chondroitin sulfate (pNIPAAm-CS) for biocompatibility and temperature-responsive behavior (∼32 ​°C lower critical solution temperature (<em>LCST</em>)). Rheological and small-angle X-ray scattering (SAXS) analyses confirmed EXPECT's self-healing printability and reversible LCST-driven transitions from hydrophobic (above ∼32 ​°C) to hydrophilic (below ∼32 ​°C) states. Temperature actuation (15 ​min at 25 ​°C every ∼5 days, otherwise 37 ​°C) in 10 ​mm toroid channels embedded within EXPECT guided cellular organization of cells seeded in these channels. In chondrogenic medium, actuated single mesenchymal stromal cells (MSCs) showed ∼50 ​% narrower patterns by day 7, sustained to day 36 (<em>p</em> ​&lt; ​0.001 vs. static, which widened to 137 ​± ​20 ​%). Actuated MSC spheroids elongated, forming bipedal shapes and fusing into extended patterns (length 480 ​± ​158 ​μm, <em>p</em> ​&lt; ​0.0001) over 36 days. In 14-day human umbilical vein endothelial cells (HUVEC)-MSC co-cultures (10:1), actuation reduced pattern width by 27.5 ​% (<em>p</em> ​= ​0.0236), promoted early protrusions, and decreased cell circularity (vs. 2 ​% increase in static, <em>p</em> ​= ​0.0173), indicating enhanced elongation and potential vascularization. EXPECT's dynamic, actuation-mediated control of anisotropic cell organization overcomes limitations of static hydrogels, offering significant potential for engineering complex, organized tissues in regenerative medicine.</div></div>","PeriodicalId":22019,"journal":{"name":"Smart Materials in Medicine","volume":"6 3","pages":"Pages 347-367"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145424472","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}