ACS Biomaterials Science & Engineering最新文献

{"title":"Click-Chemistry-Enabled Functionalization of Cellulose Nanocrystals with Single-Stranded DNA for Directed Assembly","authors":"Daria Bukharina, Katherine Cauffiel, Laura Mae Killingsworth, Justin A. Brackenridge, Valeriia Poliukhova, Minkyu Kim, Justin Brower, Julio Bernal-Chanchavac, Nicholas Stephanopoulos, Vladimir V. Tsukruk","doi":"10.1021/acsbiomaterials.4c01518","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01518","url":null,"abstract":"Controlling the self-assembly of cellulose nanocrystals (CNCs) requires precise control over their surface chemistry for the directed assembly of advanced nanocomposites with tailored mechanical, thermal, and optical properties. In this work, in contrast to traditional chemistries, we conducted highly selective click-chemistry functionalization of cellulose nanocrystals with complementary DNA strands via a three-step hybridization-guided process. By grafting terminally functionalized oligonucleotides through copper-free click chemistry, we successfully facilitated the assembly of brushlike DNA-modified CNCs into bundled nanostructures with distinct chiral optical dichroism in thin films. The complexation behavior of grafted DNA chains during the evaporation-driven formation of ultrathin films demonstrates the potential for mediating chiral interactions between the DNA-branched nanocrystals and their assembly into chiral bundles. Furthermore, we discuss the future directions and challenges that include new avenues for the development of functional, responsive, and bioderived nanostructures capable of dynamic reconfiguration via selective complexation, further surface modification strategies, mitigating diverse CNC aggregation, and exploring environmental conditions for the CNC–DNA assembly.","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142205665","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":"Development of Tissue-Engineered Model of Fibrotic Scarring after Spinal Cord Injury to Study Astrocyte Activation and Neurite Outgrowth In Vitro","authors":"Nikolas Ala-Kokko, Inha Baek, Younghye Song","doi":"10.1021/acsbiomaterials.4c01100","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01100","url":null,"abstract":"Traumatic spinal cord injuries (SCI) are debilitating injuries affecting twenty-seven million people worldwide and cause functional impairments. Despite decades of research and medical advancements, current treatment options for SCI remain limited, in part due to the complex pathophysiology of spinal cord lesions including cellular transformation and extracellular matrix (ECM) remodeling. Recent studies have increased focus on fibrotic scarring after SCI, and yet much remains unclear about the impact of fibrotic scarring on SCI lesion progression. Here, using collagen and decellularized spinal cord-based composite hydrogels, a three-dimensional (3D) cell culture model mimicking the fibrous core of spinal cord lesions was implemented to investigate its influence on the surrounding astrocytes. To mimic the fibrotic milieu, collagen fibril thickness was tuned using previously established temperature-controlled casting methods. In our platforms, astrocytes in fibro-mimetic hydrogels exhibited increased levels of activation markers such as glial fibrillary acidic protein and N-cadherin. Furthermore, astrocytes in fibro-mimetic hydrogels deposited more fibronectin and laminin, further hinting that astrocytes may also contribute to fibrotic scarring. These markers were decreased when Rho-ROCK and integrin β1 were inhibited via pharmacological inhibitors. Mechanistic analysis of Yes-associated protein reveals that blocking integrin β1 prevents mechanosensing of astrocytes, contributing to altered phenotypes in variable culture conditions. In the presence of these inhibitors, astrocytes increased the secretion of brain-derived neurotrophic factor, and a greater degree of dorsal root ganglia neurite infiltration into the underlying hydrogels was observed. Altogether, this study presents a novel tissue-engineered platform to study fibrotic scarring after SCI and may be a useful platform to advance our understanding of SCI lesion aggravation.","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142205664","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":"Doxorubicin-Intercalated Li–Al-Based LDHs as Potential Drug Delivery Nanovehicle with pH-Responsive Therapeutic Cargo for Tumor Treatment","authors":"Swapan Maity, Dipesh Kumar Dubey, Jairam Meena, Anusmita Shekher, Ram Sharan Singh, Pralay Maiti","doi":"10.1021/acsbiomaterials.4c01289","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01289","url":null,"abstract":"Clinical oncology is currently experiencing a technology bottleneck due to the expeditious evolution of therapy defiance in tumors. Although drugs used in chemotherapy work for a sort of cell death with potential clinical application, the effectiveness of chemotherapy-inducing drugs is subject to several endogenous conditions when used alone, necessitating the urgent need for controlled mechanisms. A tumor-targeted drug delivery therapy using Li–Al (M⁺/M³⁺)-based layered double hydroxide (LDHs) family has been proposed with the general chemical formula [M⁺_1–<i>x</i> M³⁺_<i>x</i> (OH)]^2<i>x</i>+[(A^<i>m–</i>)_{2<i>x</i>/<i>m</i>}. <i>n</i>(H₂O)]^2<i>x</i>−, which is fully biodegradable and works in connection with the therapeutic interaction between LDH nanocarriers and anticancerous doxorubicin (DOX). Compositional variation of Li and Al in LDHs has been used as a nanoplatform, which provides a functional balance between circulation lifetime, drug loading capacity, encapsulation efficiency, and tumor-specific uptake to act as self-regulatory therapeutic cargo to be released intracellularly. First-principle analyses based on DFT have been employed to investigate the interaction of bonding and electronic structure of LDH with DOX and assess its capability and potential for a superior drug carrier. Following the internalization into cancer cells, nanoformulations are carried to the nucleus via lysosomes, and the mechanistic pathways have been revealed. Additionally, in vitro along with in vivo therapeutic assessments on melanoma-bearing mice show a dimensional effect of nanoformulation for better biocompatibility and excellent synergetic anticancer activity. Further, the severe toxic consequences associated with traditional chemotherapy have been eradicated by using injectable hydrogel placed just beneath the tumor site, and regulated release of the drug has been confirmed through protein expression applying various markers. However, Li–Al-based LDH nanocarriers open up new design options for multifunctional nanomedicine, which has intriguing potential for use in cancer treatment through sustained drug delivery.","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142205669","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":"Aggregation-Induced Emission-Active Organic Nanoagent with High Photothermal Conversion Efficiency for Near-Infrared Imaging-Guided Tumor Photothermal Therapy","authors":"Qiang Zhang, Enqi Li, Youwei Zhang, Yunyan Chen, Dongmei Wang, Shaozhen Wang","doi":"10.1021/acsbiomaterials.4c00959","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c00959","url":null,"abstract":"Photothermal therapy (PTT) provides a great prospect for noninvasive cancer therapy. However, it is still highly challenging to construct photothermal agents (PTAs) with the desired performances for imaging-guided PTT applications. Herein, a D–A–D-type naphthalene diamine (NDI)-based photothermal nano-PTAs NDS-BPN NP with near-infrared region (NIR) emission at 822 nm, aggregation-induced emission (AIE), high photothermal conversion efficiency (55.05%), and excellent photothermal stability is successfully designed and prepared through a simple two-step engineering method by using a new AIE molecule NDS-BPN and DSPE-PEG2000 as precursors. The prepared PTT nanoagents NDS-BPN NPs have been further applied for efficient photothermal ablation of cancer cells in vitro and also achieved the NIR fluorescent image-guided PTT tumor therapy in vivo with satisfactory results. We believe that this work provides an attractive NIR AIE NDI-based nano-PTA for the phototherapy of tumors as well as develops the construction strategy of NDI molecular-based photothermal nanoagents with desired performances for imaging-guided PTT.","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142205670","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":"Advances in Mussel Adhesion Proteins and Mussel-Inspired Material Electrospun Nanofibers for Their Application in Wound Repair","authors":"Qiqi Dai, Huazhen Liu, Chuang Gao, Wenbin Sun, Chunxiang Lu, Yi Zhang, Weihuang Cai, Hao Qiao, Aoxiang Jin, Yeping Wang, Yuanyuan Liu","doi":"10.1021/acsbiomaterials.4c01378","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01378","url":null,"abstract":"Mussel refers to a marine organism with strong adhesive properties, and it secretes mussel adhesion protein (MAP). The most vital feature of MAP is the abundance of the 3,4-dihydroxyphenylalanine (DOPA) group and lysine, which have antimicrobial, anti-inflammatory, antioxidant, and cell adhesion-promoting properties and can accelerate wound healing. Polydopamine (PDA) is currently the most widely used mussel-inspired material characterized by good adhesion, biocompatibility, and biodegradability. It can mediate various interactions to form functional coatings on cell-material surfaces. Nanofibers based on MAP and mussel-inspired materials have been exerting a vital role in wound repair, while there is no comprehensive review presenting them. This Review introduces the structure of MAPs and their adhesion mechanisms and mussel-inspired materials. Second, it introduces the functionalized modification of MAPs and their inspired materials in electrospun nanofibers and application in wound repair. Finally, the future development direction and coping strategies of MAP and mussel-inspired materials are discussed. Moreover, this Review can offer novel strategies for the application of nanofibers in wound repair and bring about new breakthroughs and innovations in tissue engineering and regenerative medicine.","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142205671","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":"Functionalized Polysaccharides Improve Sensitivity of Tyramide/Peroxidase Proximity Labeling Assays through Electrostatic Interactions.","authors":"Malvina Heiniger, Rosario Vanella, Zarah Walsh-Korb, Michael A Nash","doi":"10.1021/acsbiomaterials.4c00895","DOIUrl":"10.1021/acsbiomaterials.4c00895","url":null,"abstract":"<p><p>High-throughput assays that efficiently link genotype and phenotype with high fidelity are key to successful enzyme engineering campaigns. Among these assays, the tyramide/peroxidase proximity labeling method converts the product of an enzymatic reaction of a surface expressed enzyme to a highly reactive fluorescent radical, which labels the cell surface. In this context, maintaining the proximity of the readout reagents to the cell surface is crucial to prevent crosstalk and ensure that short-lived radical species react before diffusing away. Here, we investigated improvements in tyramide/peroxidase proximity labeling for enzyme screening. We modified chitosan (Cs) chains with horseradish peroxidase (HRP) and evaluated the effects of these conjugates on the efficiency of proximity labeling reactions on yeast cells displaying d-amino acid oxidase. By tethering HRP to chitosan through different chemical approaches, we localized the auxiliary enzyme close to the cell surface and enhanced the sensitivity of tyramide-peroxidase labeling reactions. We found that immobilizing HRP onto chitosan through a 5 kDa PEG linker improved labeling sensitivity by over 3.5-fold for substrates processed with a low turnover rate (e.g., d-lysine), while the sensitivity of the labeling for high activity substrates (e.g., d-alanine) was enhanced by over 0.6-fold. Such improvements in labeling efficiency broaden the range of enzymes and conditions that can be studied and screened by tyramide/peroxidase proximity labeling.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141909684","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":"Cell-Material Interactions in Covalent Adaptable Thioester Hydrogels.","authors":"Shivani Desai, Benjamin Carberry, Kristi S Anseth, Kelly M Schultz","doi":"10.1021/acsbiomaterials.4c00884","DOIUrl":"10.1021/acsbiomaterials.4c00884","url":null,"abstract":"<p><p>Covalent adaptable networks (CANs) are polymeric networks with cross-links that can break and reform in response to external stimuli, including pH, shear, and temperature, making them potential materials for use as injectable cell delivery vehicles. In the native niche, cells rearrange the extracellular matrix (ECM) to undergo basic functions including migration, spreading, and proliferation. Bond rearrangement enables these hydrogels to mimic viscoelastic properties of the native ECM which promote migration and delivery from the material to the native tissue. In this work, we characterize thioester CANs to inform their design as effective cell delivery vehicles. Using bulk rheology, we characterize the rearrangement of these networks when they are subjected to strain, which mimics the strain applied by a syringe, and using multiple particle tracking microrheology (MPT) we measure cell-mediated remodeling of the pericellular region. Thioester networks are formed by photopolymerizing 8-arm poly(ethylene glycol) (PEG)-thiol and PEG-thioester norbornene. Bulk rheology measures scaffold properties during low and high strain and demonstrates that thioester scaffolds can recover rheological properties after high strain is applied. We then 3D encapsulated human mesenchymal stem cells (hMSCs) in thioester scaffolds. Using MPT, we characterize degradation in the pericellular region. Encapsulated hMSCs degrade these scaffolds within ≈4 days post-encapsulation. We hypothesize that this degradation is mainly due to cytoskeletal tension that cells apply to the matrix, causing adaptable thioester bonds to rearrange, leading to degradation. To verify this, we inhibited cytoskeletal tension using blebbistatin, a myosin-II inhibitor. Blebbistatin-treated cells can degrade these networks only by secreting enzymes including esterases. Esterases hydrolyze thioester bonds, which generate free thiols, leading to bond exchange. Around treated cells, we measure a decrease in the extent of pericellular degradation. We also compare cell area, eccentricity, and speed of untreated and treated cells. Inhibiting cytoskeletal tension results in significantly smaller cell area, more rounded cells, and lower cell speeds when compared to untreated cells. Overall, this work shows that cytoskeletal tension plays a major role in hMSC-mediated degradation of thioester networks. Cytoskeletal tension is also important for the spreading and motility of hMSCs in these networks. This work informs the design of thioester scaffolds for tissue regeneration and cell delivery.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015459","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":"Visible-Light-Induced Silk Fibroin Hydrogels with Carbon Quantum Dots as Initiators for 3D Bioprinting Applications.","authors":"Shuming Liu, Chunhua Ge, Zhiqiang Li, Jinyao Shan, Keke Chen, Xuefeng Li, Yu Liu, Xiangdong Zhang","doi":"10.1021/acsbiomaterials.4c01189","DOIUrl":"10.1021/acsbiomaterials.4c01189","url":null,"abstract":"<p><p>Digital light processing (DLP) 3D bioprinting technology has attracted increasing attention in tissue engineering in recent years. However, it still faces significant technical and operational challenges such as cell carcinogenesis caused by prolonged exposure to ultraviolet light and the presence of heavy metal ions in complex photoinitiator systems. In this study, a novel strategy is designed to introduce carbon quantum dots into visible-light-induced silk fibroin bioink as initiators (CDs/SilMA) applied for DLP 3D bioprinting technology. The incorporation of carbon quantum dots facilitates the formation of precise hydrogel structures at 415 nm visible wavelength, enabling the creation of brain, bronchus, spine, and ear models. Replacing heavy metal photoinitiators with carbon quantum dots imparts fluorescence properties to the bioink and enhances its mechanical properties. Meanwhile, the fibroin protein-based hydrogel exhibits favorable properties, such as drug loading, slow release, degradability, and biocompatibility. This is the first study to propose the application of carbon quantum dots in silk fibroin-based bioink. Moreover, the resulting product demonstrates excellent compatibility with the DLP printing process, making it promising for practical applications in various tissue engineering scenarios with specific requirements.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142015482","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":"Biological Functions of Macromolecular Protein Hydrogels in Constructing Osteogenic Microenvironment.","authors":"Yihan Wang, Huixin Lv, Sicong Ren, Jiameng Zhang, Xiuyu Liu, Sheng Chen, Jingjie Zhai, Yanmin Zhou","doi":"10.1021/acsbiomaterials.4c00910","DOIUrl":"10.1021/acsbiomaterials.4c00910","url":null,"abstract":"<p><p>Irreversible bone defects resulting from trauma, infection, and degenerative illnesses have emerged as a significant health concern. Structurally and functionally controllable hydrogels made by bone tissue engineering (BTE) have become promising biomaterials. Natural proteins are able to establish connections with autologous proteins through unique biologically active regions. Hydrogels based on proteins can simulate the bone microenvironment and regulate the biological behavior of stem cells in the tissue niche, making them candidates for research related to bone regeneration. This article reviews the biological functions of various natural macromolecular proteins (such as collagen, gelatin, fibrin, and silk fibroin) and highlights their special advantages as hydrogels. Then the latest research trends on cross-linking modified macromolecular protein hydrogels with improved mechanical properties and composite hydrogels loaded with exogenous micromolecular proteins have been discussed. Finally, the applications of protein hydrogels, such as 3D printed hydrogels, microspheres, and injectable hydrogels, were introduced, aiming to provide a reference for the repair of clinical bone defects.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034441","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":"Three-Dimensional Lymphatics-on-a-Chip Reveals Distinct, Size-Dependent Nanoparticle Transport Mechanisms in Lymphatic Drug Delivery.","authors":"Renhao Lu, Benjamin J Lee, Esak Lee","doi":"10.1021/acsbiomaterials.4c01005","DOIUrl":"10.1021/acsbiomaterials.4c01005","url":null,"abstract":"<p><p>Although nanoparticle-based lymphatic drug delivery systems promise better treatment of cancer, infectious disease, and immune disease, their clinical translations are limited by low delivery efficiencies and unclear transport mechanisms. Here, we employed a three-dimensional (3D) lymphatics-on-a-chip featuring an engineered lymphatic vessel (LV) capable of draining interstitial fluids including nanoparticles. We tested lymphatic drainage of different sizes (30, 50, and 70 nm) of PLGA-<i>b</i>-PEG nanoparticles (NPs) using the lymphatics-on-a-chip device. In this study, we discovered that smaller NPs (30 and 50 nm) transported faster than larger NPs (70 nm) through the interstitial space, as expected, but the smaller NPs were captured by lymphatic endothelial cells (LECs) and accumulated within their cytosol, delaying NP transport into the lymphatic lumen, which was not observed in larger NPs. To examine the mechanisms of size-dependent NP transports, we employed four inhibitors, dynasore, nystatin, amiloride, and adrenomedullin, to selectively block dynamin-, caveolin-, macropinocytosis-mediated endocytosis-, and cell junction-mediated paracellular transport. Inhibiting dynamin using dynasore enhanced the transport of smaller NPs (30 and 50 nm) into the lymphatic lumen, minimizing cytosolic accumulation, but showed no effect on larger NP transport. Interestingly, the inhibition of caveolin by nystatin decreased the lymphatic transport of larger NPs without affecting the smaller NP transport, indicating distinct endocytosis mechanisms used by different sizes of NPs. Macropinocytosis inhibition by amiloride did not change the drainage of all sizes of NPs; however, paracellular transport inhibition by adrenomedullin blocked the lymphatic transport of NPs of all sizes. We further revealed that smaller NPs were captured in the Rab7-positive late-stage lymphatic endosomes to delay their lymphatic drainage, which was reversed by dynamin inhibition, suggesting that Rab7 is a potential target to enhance the lymphatic delivery of smaller NPs. Together, our 3D lymphatics-on-a-chip model unveils size-dependent NP transport mechanisms in lymphatic drug delivery.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034443","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}