Acta Biomaterialia最新文献

{"title":"A multifunctional PD-L1 modulator for metabolic reprogramming to induce pyroptosis and enhance glutamine inhibition-mediated antitumor immunotherapy","authors":"Jialing Guo ,&nbsp;Ligang Wu ,&nbsp;Jieke Zhang ,&nbsp;Xiaodi Zhang ,&nbsp;Bin Du","doi":"10.1016/j.actbio.2026.01.004","DOIUrl":"10.1016/j.actbio.2026.01.004","url":null,"abstract":"<div><div>Metabolic interference strategies offer promising interventions in tumor therapy. However, inhibiting glutamine metabolism can upregulate Programmed Cell Death Ligand 1 (PD-L1), resulting in immune evasion and limiting the efficacy of glutamine inhibitors. Here, a nano-modulator with multi-enzyme interactions, DPG@COD/CuMOF@Dz, is introduced. It combines metabolic management and immunotherapy by incorporating copper metal-organic framework nanoparticles containing cholesterol oxidase (COD) and DNAzyme (Dz), as well as particles modified with DSPE-PEG-glutamine (DPG). Once internalized, the nano-modulator releases COD, Cu²⁺, and Dz in response to the high intracellular GSH environment. Cu²⁺ activates Dz, which inhibits glutaminase production and glutamine metabolism in cancer cells. Meanwhile, COD depletes cholesterol from cancer cell membranes, decreasing PD-L1 stability and abundance. COD produces hydrogen peroxide, which combines with Cu²⁺ via Fenton-like processes to produce ·OH, raising intracellular reactive oxygen species (ROS) levels. Additionally, GLS Dz effectively suppresses glutamine metabolism, thereby diminishing intracellular glutathione (GSH) synthesis and disrupting the redox homeostasis in cancer cells. These cascading events collectively initiate pyroptosis and immunogenic cell death (ICD), which not only attenuates PD-L1-mediated immune evasion but also provokes a robust antitumor immune response. Notably, combination therapy employing the nano-modulator and an αPD-1 antibody achieved a remarkable tumor inhibition rate of 93.7%. This work presents a promising strategy to overcome the challenges associated with glutamine blockade, offering an innovative therapeutic paradigm for the treatment of breast cancer.</div></div><div><h3>Statement of significance</h3><div>This study develops a novel nano-modulator (DPG@COD/CuMOF@Dz) that co-targets glutamine metabolism and PD-L1 stability via cholesterol depletion for enhanced cancer immunotherapy. By integrating enzymatic activity and metal-organic frameworks for synergistic redox disruption and immune activation, it overcomes limitations of conventional inhibitors and offers a “three-in-one” strategy to reverse immunosuppression. This work provides new insights into metabolic-immune crosstalk and presents a promising combinatory platform to boost immune checkpoint therapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 770-785"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D digital light processing bioprinting and in situ differentiation of hiPSCs for engineering cardiac tissue","authors":"Aihik Banerjee ,&nbsp;Kevin Dalsania ,&nbsp;Jonah Damian ,&nbsp;Jarnett Asuncion ,&nbsp;Arameh Masoumi ,&nbsp;Iman Noshadi","doi":"10.1016/j.actbio.2026.01.018","DOIUrl":"10.1016/j.actbio.2026.01.018","url":null,"abstract":"<div><div>The lack of physiologically relevant, reliable, scalable human cardiac tissue models remains a major barrier in cardiovascular disease research and drug development. Conventional 2D culture systems and animal models fail to accurately recapitulate the complex structure and function of the human myocardium, while current 3D strategies utilizing pre-differentiated cells face challenges in cell survival, integration, and tissue maturation. To address this critical gap, we developed FiBGel, a photocrosslinkable, choline bio-ionic liquid (BIL)-functionalized cold water fish gelatin methacryloyl (GelMA), optimized for direct 3D bioprinting of undifferentiated human induced pluripotent stem cells (hiPSCs) and subsequent <em>in situ</em> cardiac differentiation. FiBGel offered tunable mechanical and electrochemical properties, high cytocompatibility, and printability on a 3D digital light processing (DLP) bioprinter. For the first time, we report 3D DLP bioprinting of hiPSCs within FiBGel bio-ink, resulting in functional 3D cardiac tissue constructs. In contrast to 2D pre-differentiated cardiac cell encapsulation, <em>in situ</em> 3D cardiac differentiation of encapsulated hiPSCs in FiBGel constructs exhibited superior cardiac biomarker expression, sustained synchronous contractility, and long-term viability up to 4 months. This platform represents a significant advancement in stem cell-based biofabrication strategies for generating functional human tissue models for pharmacological screening, personalized disease modeling, and regenerative therapies.</div></div><div><h3>Statement of Significance</h3><div>This study reports the first ever demonstration of 3D digital light processing (DLP) bioprinting of undifferentiated human induced pluripotent stem cells (hiPSCs) encapsulated within a choline bio-ionic liquid-functionalized gelatin methacryloyl hydrogel, termed FiBGel. The bioprinted hiPSCs underwent <em>in situ</em> cardiac differentiation into functional engineered cardiac constructs. Unlike traditional methods reliant on pre-differentiated cell encapsulation, this strategy enables superior structural organization, sustained contractility, and viability over four months, an unprecedented duration for hiPSC-derived millimeter-scale cardiac constructs without external stimulation or perfusion. FiBGel combines tunable stiffness, electrochemistry, and cytocompatibility, addressing key limitations of current bio-inks. This work integrates stem cell biology, advanced biomaterials, and bioprinting to establish an <em>in vitro</em> system with strong potential for drug screening, disease modeling, and regeneration.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 341-356"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering shape-memory polymer microspheres as tunable curved surfaces for stem cell fate manipulation","authors":"Ruihui Liu ,&nbsp;Hao Liu ,&nbsp;Jiajie Li ,&nbsp;Hui Xie ,&nbsp;Shaobing Zhou","doi":"10.1016/j.actbio.2026.01.024","DOIUrl":"10.1016/j.actbio.2026.01.024","url":null,"abstract":"<div><div>Biomaterials mimic extracellular matrix (ECM) in tissue regeneration by providing essential physical and biochemical cues for stem cell growth; many studies have revealed the influence of such cues on stem cell fate. However, curved surfaces, the basic geometry of organisms, have rarely been considered. Besides, existing curved platforms generally offer only fixed, non-adjustable curvatures, hindering systematic investigation of their effects on stem cell fate. Here, we design and propose shape-memory polymer (SMP) microspheres as a tunable curved platform for culturing bone marrow stromal cells (BMSCs), a good candidate in tissue engineering owing to their self-renewal capacity and multi-lineage differentiation potential. After programming by controlling deformation strains, SMP microspheres transform into ellipsoidal shapes with different curvatures (aspect ratios), constructing tunable curved surfaces for BMSCs. Results indicate that BMSCs cultured on surfaces with larger curvature (smaller aspect ratio) undergo greater nuclear deformation, and vice versa. Furthermore, the curved surfaces provided by the microspheres enhance osteogenic differentiation more effectively than flat films; the larger the curvature (the smaller the aspect ratio), the stronger the promoting effect on osteogenic differentiation. This work will inspire the integration of curved surfaces into cell platforms and scaffolds and provide a shape-memory strategy for curvature adjustment.</div></div><div><h3>Statement of significance</h3><div>This work aims at the overlooked role of substrate curvature in regulating bone marrow stromal cells (BMSCs) fate by engineering shape-memory polymer (SMP) microspheres as an emerging platform for providing tunable curvatures, overcoming the limitation that existing platforms usually offer non-adjustable curvatures, hindering systematic analysis of the effects of curvature on BMSCs fate. SMP microspheres are programmed into ellipsoidal shapes with varying curvatures, and it is found that larger curvature induces greater BMSCs nuclear deformation. Crucially, curved surfaces significantly enhance BMSCs osteogenic differentiation compared to flat surfaces, with a curvature-dependent manner; larger curvature shows stronger promotion effect on osteogenic differentiation. This work develops a curvature-tunable cell substrate using SMP microspheres; it will inspire the integration of curvature cues into tissue scaffolds and curvature adjustment by shape-memory technology.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 551-561"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-mediated blockade of nociceptive transmission by targeted liposomes for efficient cancer pain therapy","authors":"Yaqian Du ,&nbsp;Zixuan Huang ,&nbsp;Xiaodan Xu ,&nbsp;Yijie Chen ,&nbsp;Jifan Chen ,&nbsp;Tao Lin ,&nbsp;Lina Tang ,&nbsp;Guowei Wang ,&nbsp;Pintong Huang","doi":"10.1016/j.actbio.2026.01.022","DOIUrl":"10.1016/j.actbio.2026.01.022","url":null,"abstract":"<div><div>The lack of pain management for advanced pancreatic cancer resulted in severe suffering for patients at the final stage of life. Pain relief can be achieved through local injection of nerve-blocking agents, but the efficiency was attenuated by perineural barriers due to drug could hardly penetrate into peripheral nerves. To address this challenge, we here proposed a strategy of ultrasound-mediated blockade of nociceptive transmission for treating the cancer pain. To demonstrate the feasibility and effectiveness of the method, a kind of transferrin-modified liposome (TLAP) loaded with AZ23 (a TrkA inhibitor) and perfluoropentane was developed and capable of ultrasound imaging guidance and ultrasonic cavitation. After local injection around the pancreatic cancer, TLAP targets the nerves via recognizing transferrin receptor, and transforms from nanosized liposome into microbubble via liquid-to-gas phase transition when exposed to ultrasound irradiation. The following ultrasonic cavitation opens the perineural barriers, and facilitates AZ23 delivery into the nerve interior, which can be visualized under ultrasound imaging, and leads to superior efficacy of pain relief in mouse cancer pain model of pancreatic cancer. In addition, sustained retention at the injection site can be maintained for over two days, and analgesia is further reinforced through repeated ultrasound exposures, enabling effective and intensity-tunable pain control. Meanwhile, no significant systemic or local tissue damage was observed after treatment. This study presents an effective strategy to tackle the perineural barriers and provides an effective nanoplatform for cancer pain management using ultrasound.</div></div><div><h3>Statement of Significance</h3><div>Pain relief of pancreatic cancer patients can be achieved through local injection of nerve-blocking agents, but the efficiency is attenuated by perineural barriers due to drug could hardly penetrate into peripheral nerves. This study developed a kind of transferrin-modified liposome (TLAP) loaded with a TrkA inhibitor and perfluoropentane to achieve ultrasonic cavitation-induced perineural barriers destruction, and ultrasound-guided cancer pain management, which led to superior efficacy of pain relief in cancer pain model of pancreatic cancer. This study presents an effective strategy of ultrasound-mediated blockade of nociceptive transmission to tackle the perineural barriers and provides an effective nanoplatform for cancer pain management of pancreatic cancer using ultrasound.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 709-723"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Mitochondria-targeted manganese-based mesoporous silica nanoplatforms trigger cGAS-STING activation and sensitize anti PD-L1 therapy in triple-negative breast cancer” [Acta Biomaterialia 199 (2025) 374–386]","authors":"Nan Zhong ,&nbsp;Ziyue Zu ,&nbsp;Yishi Lu ,&nbsp;Xuan Sha ,&nbsp;Yang Li ,&nbsp;Yang Liu ,&nbsp;Shangyu Lu ,&nbsp;Xi Luo ,&nbsp;Yan Zhou ,&nbsp;Jun Tao ,&nbsp;Feiyun Wu ,&nbsp;Zhaogang Teng ,&nbsp;Yuxia Tang ,&nbsp;Shouju Wang","doi":"10.1016/j.actbio.2026.01.008","DOIUrl":"10.1016/j.actbio.2026.01.008","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 870-871"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146004975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanotechnology-driven biomaterials for chronic liver diseases: Stage-specific strategies for advanced theranostics","authors":"Yishui Cai ,&nbsp;Tianqi Nie ,&nbsp;Xi Luo ,&nbsp;Yiqun Wu ,&nbsp;Jun Wu","doi":"10.1016/j.actbio.2026.01.043","DOIUrl":"10.1016/j.actbio.2026.01.043","url":null,"abstract":"<div><div>Chronic liver diseases (CLDs), encompassing a spectrum from steatosis and inflammation to fibrosis, cirrhosis, represent a major global health burden, causing approximately 2 million deaths annually [<span><span>1</span></span>]. The management of CLDs is significantly hampered by the limitations of conventional approaches, including non-targeted drug delivery, systemic toxicity, and inadequate diagnostic sensitivity for early-stage lesions. Nanotechnology-driven biomaterial platforms have emerged as pioneering solutions to these challenges, enabling precise theranostic strategies tailored to the distinct pathophysiology of each disease stage. This review systematically elaborates on these advancements by aligning with the natural progression of CLDs [non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatitis B, liver fibrosis, and cirrhosis]. We detail how engineered platforms enhance therapeutic efficacy by achieving superior hepatic accumulation, controlled drug release, and improved metabolic, antiviral, and antifibrotic effects. Concurrently, we explore their role in diagnostics, where nanotechnology-enhanced imaging agents and nanosensors provide unprecedented sensitivity for early detection and accurate staging. By structuring the discussion around the evolving clinical needs from NAFLD and hepatitis to advanced fibrosis and cirrhosis, this review offers a stage-specific roadmap of biomaterial design principles. It aims to provide a foundational theory and forward-looking perspectives for developing next-generation, precision medicine solutions for CLDs, ultimately bridging the gap between benchtop innovation and clinical translation.</div></div><div><h3>Statement of Significance</h3><div>This review establishes a stage-specific design paradigm that bridges the gap between biomaterial innovation and the clinical continuum of chronic liver diseases (CLDs). Its significance lies in aligning cutting-edge biomaterial strategies from targeted, stimuli-responsive nanotherapeutics to engineered exosomes and gene delivery systems with the distinct pathophysiological features of each disease stage. This approach moves beyond cataloging materials to critically evaluating their translational feasibility. We analyze how rational material design addresses specific clinical bottlenecks, such as improving drug bioavailability to diseased tissue or enabling sensitive, non-invasive diagnostics for early detection. By providing this clinically focused roadmap, this review aims to accelerate the development of personalized therapies and reshape the theranostic landscape, striving to improve therapeutic outcomes of CLDs.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 103-123"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decellularized liver matrix-based bioactive beads induce host-vasculature integrated embolization","authors":"Yutao Ma ,&nbsp;Zeyong Liu ,&nbsp;Fan Yao ,&nbsp;Man Huang ,&nbsp;Yingnan Li ,&nbsp;Peng Shi ,&nbsp;Qiongyu Guo","doi":"10.1016/j.actbio.2025.12.042","DOIUrl":"10.1016/j.actbio.2025.12.042","url":null,"abstract":"<div><div>Particle-based embolic agents are widely utilized in transarterial embolization (TAE) treatment. Currently available embolic particles are predominantly categorized as either non-degradable materials designed for permanent vascular occlusion or purely degradable materials intended for temporary embolization. Nevertheless, these embolic agents generally possess no inherent bioactivity to regulate the vascular microenvironment, thereby limiting their therapeutic efficacy. Here we developed gelatin-based bioactive embolic beads chemically conjugated with decellularized liver extracellular matrix to enable stable delivery of abundant regenerative biomolecular cues to the locoregional intra-arterial environment. Endovascular embolization of the bioactive embolic beads allowed the delivered regenerative factors to promote significant intravascular collagen deposition and neotissue formation, thereby ultimately achieving host-vasculature integrated embolization. Rabbit ear embolization model revealed endovascular integration in surrounding fine vessels as early as 5 days post-embolization, followed by complete integration in main vascular branches and full removal of the embolized target tissue within 30 days, demonstrating a remarkable improvement over clinically-used purely-biodegradable embolic particles. Such bioactive composite embolic system presents a promising platform for enhancing endovascular embolization performance.</div></div><div><h3>Statement of significance</h3><div>This study explores the therapeutic potential of a decellularized liver extracellular matrix (ECM) as a bioactive component in embolic agents for transarterial embolization treatment. Unlike conventional embolic materials that solely induce physical occlusion, the ECM derived from a regenerative organ serves as a natural healing stimulus within the vascular microenvironment post-embolization. We demonstrate, for the first time, that encapsulation of the decellularized liver matrix promotes host-vasculature integration by enhancing collagen deposition and facilitating neotissue formation. This process induces a comprehensive embolization effect, effectively occluding not only the target vessels but also the surrounding microvasculature, thereby preventing revascularization through collateral feeding vessels and achieving superior therapeutic efficacy. This work opens a therapeutic avenue by enabling controlled vascular remodeling with bioactive embolic agents to enhance endovascular embolization therapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 327-340"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the egg glue protein from two belostomatidae family aquatic water bugs, Appasus japonicus and Lethocerus indicus","authors":"Nayoung Kwon ,&nbsp;SooHo Rho ,&nbsp;Ju-Yeong Yun ,&nbsp;Susie Cho ,&nbsp;Chae Won Park ,&nbsp;Si Hyeock Lee ,&nbsp;Ju Hyeon Kim ,&nbsp;SangYoun Park","doi":"10.1016/j.actbio.2025.12.052","DOIUrl":"10.1016/j.actbio.2025.12.052","url":null,"abstract":"<div><div>Egg glue proteins are essential for the survival of aquatic insects, as they provide the means for securely attaching eggs to substrates and preventing them from being dislodged by water. In this study, we aimed to identify and characterize the egg glue proteins from two species of Belostomatidae family aquatic insects, <em>Appasus japonicus</em> and <em>Lethocerus indicus</em>, which are both commonly known as \"toe biters\" or “(giant) water bugs”. Both species exhibit unique adhesive strategies to secure their eggs in their respective environments: <em>A. japonicus</em> lay eggs on the back of the male, often being submerged underwater, while <em>L. indicus</em> deposit eggs on vegetation above the waterline. Using proteomic approaches, including mass spectrometry and amino acid analysis, we identified the cysteine-rich glue protein from the egg mass of <em>A. japonicus</em>. Using this sequence, an orthologous protein in the <em>L. indicus</em> genome was found, and the two proteins recombinantly produced for further study. As expected, the <em>A. japonicus</em> egg glue protein showed greater water-resistance than that of <em>L. indicus</em> with similar adhesive strengths in both dry and wet conditions. In addition, circular dichroism experiment and infrared spectroscopy suggested that structural transition takes place during the curing process to result in a higher level of β-sheet in the solid form.</div></div><div><h3>Statement of Significance</h3><div>Aquatic insects keep their eggs securely attached near watery environments, but the glue they use has remained largely unstudied at the molecular level. This research identifies and analyzes the egg glue proteins of two “giant water bugs” with different egg-laying strategies: <em>Appasus japonicus</em>, which lays eggs on the backs of males, and <em>Lethocerus indicus</em>, which attaches eggs to plant stalks. We discovered that the cysteine-rich glue protein in each species is ∼13 kDa in size sharing ∼62% identity in their amino acid sequence. We also found that their adhesiveness relies on disulfide bonding between cysteine residues. This work expands our understanding of insect reproductive strategies and exemplifies another protein-based water-resistant adhesion, which may benefit in designing bioadhesives.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 535-550"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in ocular implants: From geometry design to controlled drug release mechanisms","authors":"Hongshuang Liu ,&nbsp;Jiani Zhou ,&nbsp;Lin Du ,&nbsp;Qi Chen ,&nbsp;Quanyong Yi ,&nbsp;Wei Sun","doi":"10.1016/j.actbio.2026.01.006","DOIUrl":"10.1016/j.actbio.2026.01.006","url":null,"abstract":"<div><div>The unique physiological barriers within the eye greatly impede the effective delivery of traditional drug therapies to specific intraocular target sites, leading to low bioavailability and a short duration of action. Intraocular implants placed at targeted locations via minimally invasive surgery can directly bypass these barriers. Moreover, these implants employ their morphological features to facilitate long-term, stable, and controlled drug release at the disease site. This review systematically covers the preparation processes and drug release characteristics of sheet-shaped, irregular-shaped, and cylindrical implants. Lamellar implants with a large surface area offer rapid drug release, thereby enhancing therapeutic efficiency; irregular implants provide more precise and personalized therapeutic solutions by adapting to the anatomical structure of the eye; and cylindrical implants demonstrate stable and slow release with a uniform diffusion pathway, which can maintain the drug concentration for several months. The in-depth discussion of the release mechanism regarding the implant-based drug delivery is also included. Nevertheless, contemporary research on ocular implants continues to encounter challenges, including limited drug-loading capacity and inadequate accuracy in predicting <em>in vivo</em> release kinetics. In the future, a combination of computational simulation, smart-responsive materials, and nanotechnology with the current strategies for implant preparation will be necessary to optimize implant design and accelerate their translation to clinical applications.</div></div><div><h3>Statement of significance</h3><div>The field of ocular drug delivery faces persistent challenges in overcoming physiological barriers. Ocular implants, when placed at targeted sites via minimally invasive surgery, can bypass these barriers directly. Their tailored geometries and controlled release mechanisms further enable long-acting therapeutic strategies. The current review systematically elaborates on drug release kinetics and tissue integration capacity of ocular implants with different geometric characteristics, <em>e.g.</em>, sheet-shaped, cylindrical, and irregular implants. By stating current advances and addressing existing research gaps, this review aims to establish a theoretical framework for the rational design of ocular implants, ultimately facilitating the improvement of clinical outcomes in the management of ocular diseases.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 124-144"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local mechanobiological disruption in solid tumor-driven vascular permeability: A competition between mechanical vs chemical stimuli","authors":"Alejandro Martín-Contreras ,&nbsp;María Sarasquete-Martínez ,&nbsp;José Manuel García-Aznar ,&nbsp;Alejandra González-Loyola ,&nbsp;María José Gómez-Benito","doi":"10.1016/j.actbio.2026.01.013","DOIUrl":"10.1016/j.actbio.2026.01.013","url":null,"abstract":"<div><div>The tumor microenvironment imposes complex biochemical and biomechanical constraints on microvasculature, contributing to aberrant tumor blood vessels, characterized by abnormal endothelial proliferation, disrupted cell-to-cell junctions and increased permeability. While vascular normalization strategies have traditionally focused on biochemical modulation, the role of mechanical forces in endothelial dysfunction remains unclear. Here, we used a microfluidic platform to dissect the mechanobiological impact of two distinct solid tumor models —pancreatic ductal adenocarcinoma (PANC-1) and lung adenocarcinoma (A549)—on three-dimensional embedded endothelial vessels. Our findings reveal that PANC-1 spheroids exert significant mechanical forces, expanding vessel diameter and disrupting endothelial barrier integrity via cellular contractility. Conversely, A549 spheroids contribute to vascular destabilization through biochemical modulation, primarily via extracellular matrix degradation and inflammatory secretomes, leading to an altered and heterogeneous endothelial permeability. Proteomic analysis of both tumor cell lines highlights distinct pathways involved in endothelial remodeling: cytoskeletal alterations and consequent stresses in pancreatic ductal adenocarcinoma, while extracellular matrix remodeling and pro-inflammatory microenvironment are found in lung adenocarcinoma. These insights underscore the necessity of tumor-specific vascular normalization strategies, combining mechanobiological and biochemical approaches to restore endothelial barrier function. Our locally controlled microfluidic approach provides a versatile platform for evaluating innovative therapeutic strategies targeting tumor-specific vasculature.</div></div><div><h3>Statement of significance</h3><div>This study highlights the often-overlooked role of tumor-derived mechanical forces in vascular dysfunction. Within the tumor microenvironment, different tumor types disrupt the endothelial barrier through distinct, tumor-specific mechanisms, leading to varied patterns of vessel instability. Using confocal microscopy, we achieved spatially resolved analysis of local endothelial barrier damage, distinguishing focal from diffuse permeability changes. A 3D microfluidic platform was developed to replicate tumor endothelium interactions, combining live imaging, morphometric and biochemical assays, and proteomic profiling. This integrative model offers a versatile tool for evaluating drug responses under controlled mechanochemical conditions, supporting the development of personalized vascular-targeted therapies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 413-427"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}