Journal of Materials Chemistry B最新文献

{"title":"Magnetic lanthanide sensor with self-ratiometric time-resolved luminescence for accurate detection of epithelial cancerous exosomes†","authors":"Yating Zeng, Xuekang Wang, Nanhang Zhu, Yue Yu, Xingyou Wang, Ke Kang, Yao Wu and Qiangying Yi","doi":"10.1039/D4TB00497C","DOIUrl":"10.1039/D4TB00497C","url":null,"abstract":"<p >Fluorescence-based LB (liquid biopsy) offers a rapid means of detecting cancer non-invasively. However, the widespread issue of sample loss during purification steps will diminish the accuracy of detection results. Therefore, in this study, we introduce a magnetic lanthanide sensor (MLS) designed for sensitive detection of the characteristic protein, epithelial cell adhesion molecule (EpCAM), on epithelial tumor exosomes. By leveraging the inherent multi-peak emission and time-resolved properties of the sole-component lanthanide element, combined with the self-ratiometric strategy, MLS can overcome limitations imposed by manual operation and/or sample complexity, thereby providing more stable and reliable output results. Specifically, terbium-doped NaYF<small>₄</small> nanoparticles (NaYF<small>₄</small>:Tb) and deformable aptamers terminated with BHQ1 were sequentially introduced onto superparamagnetic silica-decorated Fe<small>₃</small>O<small>₄</small> nanoparticles. Prior to target binding, emission from NaYF<small>₄</small>:Tb at 543 nm was partially quenched due to the fluorescence resonance energy transfer (FRET) from NaYF<small>₄</small>:Tb to BHQ1. Upon target binding, changes in the secondary structure of aptamers led to the fluorescence intensity increasing since the deconfinement of distance-dependent FRET effect. The characteristic emission of NaYF<small>₄</small>:Tb at 543 nm was then utilized as the detection signal (<em>I</em><small>₁</small>), while the less changed emission at 583 nm served as the reference signal (<em>I</em><small>₂</small>), further reporting the self-ratiometric values of <em>I</em><small>₁</small> and <em>I</em><small>₂</small> (<em>I</em><small>₁</small>/<em>I</em><small>₂</small>) to illustrate the epithelial cancerous features of exosomes while ignoring possible sample loss. Consequently, over a wide range of exosome concentrations (2.28 × 10<small>²</small>–2.28 × 10<small>⁸</small> particles per mL), the <em>I</em><small>₁</small>/<em>I</em><small>₂</small> ratio exhibited a linear increase with exosome concentration [<em>Y</em>(<em>I</em><small>₁</small>/<em>I</em><small>₂</small>) = 0.166 lg (<em>N</em><small>_exosomes</small>) + 3.0269, <em>R</em><small>²</small> = 0.9915], achieving a theoretical detection limit as low as 24 particles per mL. Additionally, MLS effectively distinguished epithelial cancer samples from healthy samples, showcasing significant potential for clinical diagnosis.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 29","pages":" 7203-7214"},"PeriodicalIF":6.1,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and evaluation of nanoscale materials with programmed responsivity towards epigenetic enzymes†","authors":"Priyanka Ray, Abbas Sedigh, Matthew Confeld, Lina Alhalhooly, Kweeni Iduoku, Gerardo M. Casanola-Martin, Hai Pham-The, Bakhtiyor Rasulev, Yongki Choi, Zhongyu Yang, Sanku Mallik and Mohiuddin Quadir","doi":"10.1039/D4TB00514G","DOIUrl":"10.1039/D4TB00514G","url":null,"abstract":"<p >Self-assembled materials capable of modulating their assembly properties in response to specific enzymes play a pivotal role in advancing 'intelligent' encapsulation platforms for biotechnological applications. Here, we introduce a previously unreported class of synthetic nanomaterials that programmatically interact with histone deacetylase (HDAC) as the triggering stimulus for disassembly. These nanomaterials consist of co-polypeptides comprising poly(acetyl <small>L</small>-lysine) and poly(ethylene glycol) blocks. Under neutral pH conditions, they self-assemble into particles. The hydrodynamic diameters of particles were typically withing the range of 108–190 nm, depending on degree of acetylation of the hydrophobic block. However, their stability is compromised upon exposure to HDACs, depending on enzyme concentration and exposure time. Our investigation, utilizing HDAC8 as the model enzyme, revealed that the primary mechanism behind disassembly involves a decrease in amphiphilicity within the block copolymer due to the deacetylation of lysine residues within the particles' hydrophobic domains. To elucidate the response mechanism, we encapsulated a fluorescent dye within these nanoparticles. Upon incubation with HDAC, the nanoparticle structure collapsed, leading to controlled release of the dye over time. Notably, this release was not triggered by denatured HDAC8, other proteolytic enzymes like trypsin, or the co-presence of HDAC8 and its inhibitor. We also demonstrated the biocompatibility and cellular effects of these materials in the context of drug delivery in different types of anticancer cell lines, such as MIA PaCa-2, PANC-1, cancer like stem cells (CSCs), and non-cancerous HPNE cells. We observed that the release of a model drug (such as a STAT3 pathway inhibitor, Napabucasin) can be loaded into these nanoparticles, with &gt;90% of the dosage can be released over 3 h under the influence of HDAC8 enzyme in a controlled fashion. Further, we conducted a comprehensive computational study to unveil the possible interaction mechanism between enzymes and particles. By drawing parallels to the mechanism of naturally occurring histone proteins, this research represents a pioneering step toward developing functional materials capable of harnessing the activity of epigenetic enzymes such as HDACs.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 39","pages":" 9905-9920"},"PeriodicalIF":6.1,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heparin binding induced supramolecular chirality into the self-assembly of perylenediimide bolaamphiphile†","authors":"Poonam Sharma, Akhil Venugopal, Claudia Martínez Verdi, Mauri Serra Roger, Annalisa Calò and Mohit Kumar","doi":"10.1039/D4TB00862F","DOIUrl":"10.1039/D4TB00862F","url":null,"abstract":"<p >Chirality is one of the hallmarks of biomolecules. Herein, we utilize heparin, a chiral biomolecule and potent drug, to induce chiral organization into the assembly of an achiral molecule. Polyanionic heparin binds with a dicationic perylenediimide derivative to induce supramolecular helical organization in aqueous medium as well as in a highly competitive cell culture medium.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 30","pages":" 7292-7297"},"PeriodicalIF":6.1,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/tb/d4tb00862f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flexible and transparent nanohole-patterned films with antibacterial properties against Staphylococcus aureus†","authors":"Hee-Kyeong Kim, Jeong-Hun Park, Min-Jun Jang, Su-Ji Han, Young-Sam Cho and Hyun-Ha Park","doi":"10.1039/D4TB00434E","DOIUrl":"10.1039/D4TB00434E","url":null,"abstract":"<p >In this paper, we explore the development of a multi-functional surface designed to tackle the challenges posed by <em>Staphylococcus aureus</em> (<em>S. aureus</em>), a common opportunistic pathogen. Infections caused by <em>S. aureus</em> during surgical procedures highlight the need for effective strategies to inhibit its adhesion, growth, and colonization, particularly on the surfaces of invasive medical devices. Until now, most existing research has focused on nanopillar structures (positive topographies). Uniform nanopillar arrays have been shown to control bacterial behavior based on the spacing between nanopillars. However, nanopillar structures are susceptible to external friction, impact, and force, making it challenging to maintain their antibacterial properties. Therefore, in this study, we investigate the antibacterial behavior of nanohole structures, which offer relatively superior mechanical robustness compared to nanopillars. Moreover, for applications in medical devices such as laparoscopes, there is a pressing need for surfaces that are not only transparent and flexible (or curved) but are also equipped with antibacterial properties. Our study introduces a scalable multi-functional surface that synergistically combines antibacterial and anti-fog properties. This is achieved by fabricating thin films with variously sized holes (ranging from 0.3 μm to 4 μm) using polyurethane acrylate (PUA). We assessed the activity of <em>S. aureus</em> on these surfaces and found that a 1 μm-diameter-hole pattern significantly reduced the presence of live <em>S. aureus</em>, without any detection of dead <em>S. aureus</em>. This bacteriostatic effect is attributed to the restricted proliferation due to the confined area provided by the hole pattern. However, the persistence of some live <em>S. aureus</em> on the surface necessitates further measures to minimize bacterial adhesion and enhance antibacterial effectiveness. To address this challenge, we coated the zwitterionic polymer 2-methacryloyloxyethyl phosphorylcholine (MPC) onto the nanohole pattern surface to reduce <em>S. aureus</em> adhesion. Moreover, in long-term experiments on surfaces, the MPC-coated effectively inhibited the colonization of <em>S. aureus</em> (18 h; 82%, 7 days; 83%, and 14 days; 68% antibacterial rate). By integrating PUA, MPC, and nanohole architectures into a single, flexible platform, we achieved a multi-functional surface catering to transparency, anti-fogging, and anti-biofouling requirements. This innovative approach marks a significant advancement in surface engineering, offering a versatile solution applicable in various fields, particularly in preventing <em>S. aureus</em> contamination in invasive medical devices like laparoscopes. The resultant surface, characterized by its transparency, flexibility, and antibacterial functionality, stands out as a promising candidate for mitigating <em>S. aureus</em>-related risks in medical applications.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 30","pages":" 7298-7310"},"PeriodicalIF":6.1,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Europium–tannic acid nanocomplexes devised for bone regeneration under oxidative or inflammatory environments†","authors":"Daniel Fernández-Villa, María Rosa Aguilar and Luis Rojo","doi":"10.1039/D4TB00697F","DOIUrl":"10.1039/D4TB00697F","url":null,"abstract":"<p >Europium ions (Eu<small>³⁺</small>) are gaining attention in the field of regenerative medicine due to increasing evidence of their osteogenic properties. However, inflammatory and oxidative environments present in many bone diseases, such as osteoporosis or rheumatoid arthritis, are known to hinder this regenerative process. Herein, we describe a straightforward synthetic procedure to prepare Eu<small>³⁺</small>–tannic acid nanocomplexes (EuTA NCs) with modulable physicochemical characteristics, as well as antioxidant, anti-inflammatory, and osteogenic properties. EuTA NCs were rationally synthesized to present different contents of Eu<small>³⁺</small> on their structure to evaluate the effect of the cation on the biological properties of the formulations. In all the cases, EuTA NCs were stable in distilled water at physiological pH, had a highly negative surface charge (<em>ζ</em> ≈ −25.4 mV), and controllable size (80 &lt; <em>D</em><small>_h</small> &lt; 160 nm). <em>In vitro</em> antioxidant tests revealed that Eu<small>³⁺</small> complexation did not significantly alter the total radical scavenging activity (RSA) of TA but enhanced its ability to scavenge H<small>₂</small>O<small>₂</small> and ferrous ions, thus improving its overall antioxidant potential. At the cellular level, EuTA NCs reduced the instantaneous toxicity of high concentrations of free TA, resulting in better antioxidant (13.3% increase of RSA <em>vs.</em> TA) and anti-inflammatory responses (17.6% reduction of nitric oxide production <em>vs.</em> TA) on cultures of H<small>₂</small>O<small>₂</small>- and LPS-stimulated macrophages, respectively. Furthermore, the short-term treatment of osteoblasts with EuTA NCs was found to increase their alkaline phosphatase activity and their matrix mineralization capacity. Overall, this simple and tunable platform is a potential candidate to promote bone growth in complex environments by simultaneously targeting multiple pathophysiological mechanisms of disease.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 29","pages":" 7153-7170"},"PeriodicalIF":6.1,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/tb/d4tb00697f?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141478265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cationic-motif-modified exosomes for mRNA delivery to retinal photoreceptors†","authors":"Héctor A. Millán Cotto, Tanvi Vinod Pathrikar, Bill Hakim, Helna M. Baby, Hengli Zhang, Peng Zhao, Ronak Ansaripour, Rouzbeh Amini, Rebecca L. Carrier and Ambika G. Bajpayee","doi":"10.1039/D4TB00849A","DOIUrl":"10.1039/D4TB00849A","url":null,"abstract":"<p >Topical treatment of vitreoretinal diseases remains a challenge due to slow corneal uptake and systemic clearance. Exosomes are emerging nanocarriers for drug delivery due to biocompatibility and cellular targeting properties. To apply them for retinal targeting <em>via</em> the topical route, exosomes must traverse various ocular barriers including the cornea, lens, vitreous humor (VH), and the retina itself. Here we engineered high-purity milk-derived exosomes by anchoring arginine-rich cationic motifs <em>via</em> PEG<small>₂₀₀₀</small> lipid insertion on their surface. Modification enabled exosomes to use weak-reversible electrostatic interactions with anionic glycosaminoglycan (GAG) and water content of the tissue to enhance their transport rate and retention. Addition of cationic motifs neutralized the anionic surface charge of exosomes (−24 to −2 mV) without impacting size or morphology. Cationic-motif-modified exosomes exhibited two-fold faster steady state diffusivity through bovine corneas compared to unmodified exosomes. Fluorescence recovery after photobleaching confirmed that cationic-motif-modified exosomes can diffuse through VH without steric hindrance. In healthy VH, cationic-motif-modified exosomes demonstrated stronger binding resulting in three-fold lower average diffusivity that enhanced by six-fold in 50% GAG-depleted VH recapitulating advanced liquefaction. Cationic-motif-modified exosomes penetrated through the full-thickness of porcine retinal explants resulting in ten-fold higher uptake in photoreceptors and three-fold greater transfection with encapsulated eGFP mRNA compared to unmodified exosomes. Cationic-motif-modified exosomes are safe to use as they did not adversely affect the mechanical swelling properties of the cornea or lens nor impact retinal cell viability. Cationic-motif-modified exosomes, therefore, offer themselves as a cell-free nanocarrier platform for gene delivery to retinal photoreceptors potentially <em>via</em> the topical route.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 30","pages":" 7384-7400"},"PeriodicalIF":6.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A polymeric 1H/19F dual-modal MRI contrast agent with a snowman-like Janus nanostructure†","authors":"Ziwei Duan, Jialei Han, Yadong Liu, Xinyu Zhao, Bo Wang, Shuaishuai Cao and Dalin Wu","doi":"10.1039/D4TB00923A","DOIUrl":"10.1039/D4TB00923A","url":null,"abstract":"<p >Magnetic resonance imaging (MRI) has emerged as a pivotal tool in contemporary medical diagnostics, offering non-invasive and high-resolution visualization of internal structures. Contrast agents are essential for enhancing MRI resolution, accurate lesion detection, and early pathology identification. While gadolinium-based contrast agents are widely used in clinics, safety concerns have prompted exploration of metal-free alternatives, including fluorine and nitroxide radical-based MRI contrast agents. Fluorine-containing compounds exhibit excellent MRI capabilities, with <small>¹⁹</small>F MRI providing enhanced resolution and quantitative assessment. Nitroxide radicals, such as PROXYL and TEMPO, offer paramagnetic properties for MRI contrast. Despite their versatility, nitroxide radicals suffer from lower relaxivity values (<em>r</em><small>₁</small>) compared to gadolinium. Dual-modal imaging, combining <small>¹</small>H and <small>¹⁹</small>F MRI, has gained prominence for its comprehensive insights into biological processes and disease states. However, existing dual-modal agents predominantly utilize gadolinium-organic ligands without incorporating nitroxide radicals. Here, we introduce a novel dual-modal MRI contrast agent (J-CA) featuring a Janus asymmetric nanostructure synthesized <em>via</em> seeded emulsion polymerization and post-modification. J-CA demonstrates excellent <em>in vitro</em> and <em>in vivo</em> performance in both <small>¹⁹</small>F and <small>¹</small>H MRI, with a <em>T</em><small>₂</small> relaxation time of 5 ms and an <em>r</em><small>₁</small> value of 0.31 mM<small>⁻¹</small> s<small>⁻¹</small>, ensuring dual-modal imaging capability. Moreover, J-CA exhibits superior biocompatibility and organ targeting, making it a promising candidate for precise lesion imaging and disease diagnosis. This work introduces a new avenue for metal-free dual-modal MRI, addressing safety concerns associated with traditional contrast agents.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 29","pages":" 7090-7102"},"PeriodicalIF":6.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitrogen-doped carbon dots: a novel biosensing platform for selective norfloxacin detection and bioimaging†","authors":"S. Sivaselvam, R. S. Anjana, N. S. Dhujana, Marina Victor and Ramapurath S. Jayasree","doi":"10.1039/D4TB01006J","DOIUrl":"10.1039/D4TB01006J","url":null,"abstract":"<p >Incomplete metabolism and non-biodegradable nature of norfloxacin (NORx) lead to its persistent residues in the environment and food, potentially fostering the emergence of antibiotic resistance and posing a significant threat to public health. Hence, we developed a norfloxacin sensor employing hydrothermally synthesized N-doped carbon dots (N-Ch-CQDs) from chitosan and PEI demonstrated high sensitivity and specificity towards the antibiotic detection. The quantum yield of excitation-dependent emission of N-Ch-CQDs was effectively tuned from 4.6 to 21.5% by varying the concentration of PEI (5–15%). With the enhanced fluorescence in the presence of norfloxacin, N-Ch-CQDs exhibited a linear detection range of 20–1400 nM with a limit of detection (LoD) of 9.3 nM. The high biocompatibility of N-Ch-CQDs was confirmed in the <em>in vitro</em> and <em>in vivo</em> model and showed the environment-friendly nature of the sensor. Detailed study elucidated the formation of strong hydrogen bonds between N-Ch-CQDs and NORx, leading to fluorescence enhancement. The developed sensor's capability to detect NORx was evaluated in water and milk samples. The recovery rate ranged from 98.5% to 103.5%, demonstrating the sensor's practical applicability. Further, the bioimaging potential of N-Ch-CQDs was demonstrated in both the <em>in vitro</em> (L929 cells) and <em>in vivo</em> model (<em>C. elegans</em>). The synergistic influence of the defecation pattern and functioning of intestinal barrier mitigates the translocation of N-Ch-CQDs into the reproductive organ of nematodes. This study revealed the bioimaging and fluorescent sensing ability of N-Ch-CQDs, which holds significant promise for extensive application in the biomedical field.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 31","pages":" 7635-7645"},"PeriodicalIF":6.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conformal encapsulation of mammalian stem cells using modified hyaluronic acid†","authors":"Jack Whitewolf and Christopher B. Highley","doi":"10.1039/D4TB00223G","DOIUrl":"10.1039/D4TB00223G","url":null,"abstract":"<p >Micro- and nanoencapsulation of cells has been studied as a strategy to protect cells from environmental stress and promote survival during delivery. Hydrogels used in encapsulation can be modified to influence cell behaviors and direct assembly in their surroundings. Here, we report a system that conformally encapsulated stem cells using hyaluronic acid (HA). We successfully modified HA with lipid, thiol, and maleimide pendant groups to facilitate a hydrogel system in which HA was deposited onto cell plasma membranes and subsequently crosslinked through thiol-maleimide click chemistry. We demonstrated conformal encapsulation of both neural stem cells (NSCs) and mesenchymal stromal cells (MSCs), with viability of both cell types greater than 90% after encapsulation. Additional material could be added to the conformal hydrogel through alternating addition of thiol-modified and maleimide-modified HA in a layering process. After encapsulation, we tracked egress and viability of the cells over days and observed differential responses of cell types to conformal hydrogels both according to cell type and the amount of material deposited on the cell surfaces. Through the design of the conformal hydrogels, we showed that multicellular assembly could be created in suspension and that encapsulated cells could be immobilized on surfaces. In conjunction with photolithography, conformal hydrogels enabled rapid assembly of encapsulated cells on hydrogel substrates with resolution at the scale of 100 μm.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 29","pages":" 7122-7134"},"PeriodicalIF":6.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11268093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dapansutrile OLT1177 suppresses foreign body response inflammation while preserving vascularisation of implanted materials†","authors":"Alex H. P. Chan, Xueying S. Xu, Ian L. Chin, Angus J. Grant, Kieran Lau, Yunfei Hu, Praveesuda L. Michael, Yuen Ting Lam, Steven G. Wise and Richard P. Tan","doi":"10.1039/D4TB00705K","DOIUrl":"10.1039/D4TB00705K","url":null,"abstract":"<p >Mitigating inflammation associated with the foreign body response (FBR) remains a significant challenge in enhancing the performance of implantable medical devices. Current anti-inflammatory approaches aim to suppress implant fibrosis, the major outcome of the FBR, but also inadvertently inhibit beneficial immune signalling necessary for tissue healing and vascularization. In a previous study, we demonstrated the feasibility of ‘selective’ immunosuppression targeting the NLRP3 inflammasome using the small molecule inhibitor MCC950, leading to reduced implant fibrosis without compromising healing and leading to enhanced vascularization. However, the clinical potential of MCC950 is severely limited due to its failure to pass Phase I clinical safety trials. This has triggered substantial efforts to develop safer analogues of NLRP3 inhibitors. Dapansutrile (OLT1177) is emerging as a leading candidate amongst current NLRP3 inhibitors, demonstrating both safety and effectiveness in a growing number of clinical indications and Phase 2 trials. While the anti-inflammatory effects of OLT1177 have been shown, validation of these effects in the context of implanted materials and the FBR have not yet been demonstrated. In this study, we show OLT1177 possesses beneficial effects on key cell types which drive FBR outcomes, including macrophages, fibroblasts, and smooth muscle cells. Evaluation of OLT1177 in a 28 day subcutaneous implantation model showed OLT1177 reduced fibrotic capsule formation while promoting implant vascularization. Mechanistic studies revealed that this occurred through activation of early pro-angiogenic markers while suppressing late-stage anti-angiogenic markers. These findings establish OLT1177 as a promising therapeutic approach for mitigating implant fibrosis while supporting vascularisation, suggesting a highly promising selective immunosuppressive strategy for the FBR warranting further research to explore its optimal integration into medical materials and devices.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 30","pages":" 7334-7347"},"PeriodicalIF":6.1,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}