Acta biomaterialia最新文献

{"title":"Enhanced Delivery of Camptothecin to Colorectal Carcinoma Using a Tumor-Penetrating Peptide Targeting p32.","authors":"Yanhao Jiang, Zhiren Wang, Wenpan Li, Teng Ma, Mengwen Li, Shuang Wu, Ethan Lin, Karlie Elizabeth Flader, Mengjiao Ma, Mengyang Chang, Hongmin Li, Wei Wang, Jianqin Lu","doi":"10.1016/j.actbio.2025.05.036","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.036","url":null,"abstract":"<p><p>Camptothesome, a sphingomyelin (SM)-conjugated camptothecin (CPT) vesicular nanotherapeutic, addresses the poor solubility and lactone instability of CPT while enhancing drug loading, pharmacokinetics, and tumor distribution compared to CPT physically entrapped in conventional liposomes. Despite these improvements, the tumor uptake remains limited. To further enhance the tumor delivery efficiency and minimize the off-target distribution, we functionalize Camptothesome with the LinTT1 peptide, a CendR motif, which binds to overexpressed p32 proteins on tumor cell surface, initiating effective transcytosis for deep tumor penetration. Via systematic screening, the optimal peptide ratio on Camptothesome is identified. LinTT1/Camptothesome significantly increases cancer cell uptake without affecting normal cell internalization, resulting in enhanced anti-colorectal cancer cells activity. Additionally, decorating Camptothesome with the LinTT1 cell-penetrating peptide enables effective transcytosis via a Golgi-dependent intracellular trafficking mechanism, significantly improving the intratumoral delivery while reducing distribution to normal tissues. In a human HCT116 xenograft colorectal cancer (CRC) mouse model, LinTT1/Camptothesome demonstrates superior antitumor efficacy compared to both Camptothesome and Onivyde by upregulating cleaved caspase-3 and γH2AX. Our study substantiates the potential of leveraging a tumor-penetrating peptide to enhance the tumor delivery efficiency of Camptothesome, maximizing its therapeutic index for improved treatment of human CRC. STATEMENT OF SIGNIFICANCE: Despite the improved tumor delivery achieved by Camptothesome, its tumor distribution and penetration remain limited. This is because the enhanced permeability and retention effect only facilitates nanotherapeutic distribution to tumor periphery through leaky vasculature. The C-end Rule (CendR) motif-neuropilin receptor system enhances tumor-homing peptides by binding to cellular surface receptors, triggering transcytosis. Herein, LinTT1, the most potent CendR peptide that binds to the overexpressed p32 receptor on cancer cells, was effectively engineered onto Camptothesome using thiol-maleimide lipid chemistry. The LinTT1/Camptothesome significantly enhanced tumor uptake and penetration while minimizing accumulation in normal tissues, demonstrating remarkable anticancer efficacy in a human xenograft colorectal cancer model. Our findings highlight the critical role of tumor-homing peptides in unlocking the full therapeutic potential of Camptothesome.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086049","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 Chitosan-based Hydrogel to Modulate Immune Cells and Promote Periodontitis Healing in the High-Fat Diet-induced Periodontitis Rat Model.","authors":"Yi Zhu, Aiman Ali, Gabriel Mulinari Dos Santos, João Paulo Soares Franciscon, Rafael Scaf de Molon, Cynthia Goh, Edilson Erovolino, Leticia Helena Theodoro, Annie Shrestha","doi":"10.1016/j.actbio.2025.05.034","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.034","url":null,"abstract":"<p><p>Periodontitis is a multifactorial inflammatory disease driven by prolonged, dysregulated inflammation between dysbiotic microbiota and the host immune system. Risk factors such as metabolic syndrome exacerbate periodontitis progression through systemic inflammation. Current treatments primarily focus on removing pathogenic dental plaque, but subsequent healing relies mainly on the host immune response. Modulating the local immune environment, particularly dendritic cells (DCs) and T-cells, in periodontitis complicated by metabolic syndrome could enhance the healing process. The objective of this study is to develop a biomaterial-based adjuvant therapy to immunomodulate DCs and T-cells and promote healing in periodontitis complicated by metabolic syndrome. We developed and characterized a chitosan-based thermosensitive injectable self-assembled hydrogel (TISH), which exhibited an interconnected porous structure conducive to cell migration and adhesion. TISH was loaded with granulocyte-macrophage colony-stimulating factor (GM-CSF) and resveratrol (TISH(GR)), enabling sustained release over time. Mechanistically, TISH(GR) suppressed inflammatory signalling pathways (MAPKs and NF-κB) downstream of Toll-like receptor-4 in DCs. In a high-fat diet-induced periodontitis rat model, TISH(GR) administered as an adjuvant to SRP significantly alleviated periodontal inflammation and tissue destruction compared to SRP alone. TISH(GR) treatment was associated with decreased TH17 cell infiltration and elevated expression of the Tregs-associated cytokine IL-10 in the periodontium. In conclusion, TISH(GR) was developed and optimized as an injectable immunomodulatory hydrogel targeting DCs and T-cells. It demonstrated promising potential to attenuate inflammation and enhance periodontal healing, particularly in immunocompromised patients with metabolic syndrome. STATEMENT OF SIGNIFICANCE: Current treatments for periodontitis primarily focus on dental plaque removal, with healing heavily dependent on the host immune system. However, metabolic diseases can dysregulate the local immune response, exacerbating periodontal inflammation and impairing post-treatment healing. In this study, we developed a chitosan-based hydrogel designed to immunomodulate dendritic cells and T-cells, polarizing them toward an anti-inflammatory phenotype that promotes tissue repair. When administered as an adjuvant to scaling and root planing, this combination therapy significantly enhanced periodontal healing and reduced tissue damage in a high-fat diet complicated periodontitis model. These findings highlight the clinical potential of this hydrogel formulation to improve treatment outcomes, particularly in challenging clinical cases involving metabolic comorbidities.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087089","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":"The phospholipid composition of artificial lipid droplets enhances their deliverability and facilitates a broad Biodistribution in vivo and in vitro.","authors":"Z Telikani, I Amarasinghe, V Impicciche, A Nalbantlar, J Whan, K Caracciolo, J I Phillips, J L Dutton, L A Wallace, A Jamal, T A Gibson Hughes, K S Okuda, A Mechler, E A Monson, K J Helbig","doi":"10.1016/j.actbio.2025.05.002","DOIUrl":"10.1016/j.actbio.2025.05.002","url":null,"abstract":"<p><p>Artificial lipid droplets (aLDs) provide a useful tool to explore the multiple functionalities of intracellular lipid droplets (LDs). In this study we explored the dynamics and potential multidisciplinary applications of these lipid particles. We have optimised construction of fluorescently labelled aLDs to allow their tracking in various in vitro and in vivo models. Modifying the phospholipid membrane of aLDs achieved enhanced delivery efficiency to a broad range of cells with various origins leading to a wide biodistribution of aLDs to organ systems in both mice and zebrafish models. The broad targeting and stability of this new generation of aLDs holds promise to now utilise aLDs as a novel delivery system as well as offering a toolset for further investigation on intracellular LD dynamics and function. STATEMENT OF SIGNIFICANCE: Artificial lipid droplets (aLDs) are a novel nanoparticle tool for biomedical research, consisting of a phospholipid monolayer with a neutral core interior. They offer new opportunities for the delivery of lipids and proteins in vivo; however, the ability of aLD lipid composition to drive enhanced cellular delivery remains unexplored. Here, we demonstrate that enhancing aLD phospholipid complexity significantly increases in vitro cellular delivery across multiple cell types and offers broad organ biodistribution, including delivery to the brain, in both mice and zebrafish. These findings highlight aLDs as potential vehicles in both basic biological studies and therapeutic interventions. Additionally, increasing the complexity of phospholipids into alternate nanoparticles such as LNPs may enhance organ biodistribution, thus opening the field up to new opportunities for cargo to reach previously undeliverable areas.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053600","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":"Dextran guanidinylated carbon dots with antibacterial and immunomodulatory activities as eye drops for the topical treatment of MRSA-induced infectious keratitis.","authors":"Menghan Zhang, Yiyang Wang, Chenfang Miao, Shuwei Lin, Ying Zheng, Xiaoyan Lin, Yao Wang, Xinhua Lin, Xiaofeng Zhu, Shaohuang Weng","doi":"10.1016/j.actbio.2025.05.032","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.032","url":null,"abstract":"<p><p>Bacterial keratitis (BK) develops rapidly and can cause serious consequences, requiring timely and efficient treatment. As the main treatment strategy, antibiotic eye drops are still plagued by bacterial resistance by biofilms and failure to modulate immunity. Herein, dextran guanidinylated carbon dots (DG-CDs) with antimicrobial and immunomodulatory properties were developed. DG-CDs with the graphitized core-like structure with the ordered arrangement of carbon atoms and surface groups of C-N, C-O-C, and -OH were thoroughly characterized and modeled as a graphene-like sheet. DG-CDs exhibited strong antimicrobial and anti-biofilm activities with a minimum inhibitory concentration (MIC) of 5 μg/mL against methicillin-resistant Staphylococcus aureus (MRSA). Molecular docking based on well-characterized structures of DG-CDs revealed that DG-CDs had strong affinity for key bacterial proteins including FtsA, IcaA and ArgA, which were confirmed by corresponding RT-PCR and transcriptomics. Furthermore, DG-CDs regulated macrophage polarization by inhibiting the M1 subtype and promoting the transition to the M2 subtype. In vivo experiments illustrated that DG-CDs used as eye drops significantly attenuated corneal infection, enhanced the expression of anti-inflammatory factors, and effectively promoted corneal repair in MRSA-infected BK. Overall, this study provides a promising antibacterial nanomaterial with clarified properties and acting mechanism for treating BK as eye drops. STATEMENT OF SIGNIFICANCE: Besides bacterial invasion, bacterial keratitis (BK) also suffers from immune imbalance, which further impairs corneal healing. Current antibiotic eye drops are plagued by bacterial resistance and their inability to modulate immunity. Herein, dextran guanidinylated carbon dots (DG-CDs) with dual functions of antimicrobial and immunomodulatory were developed for treating MRSA infected BK. DG-CDs, with clarified structure and surface groups, exhibited strong antimicrobial activity and no detectable resistance. Molecular docking, based on well-characterized structures of DG-CDs, was achieved to reveal the antibacterial mechanism, which was subsequently confirmed by RT-PCR and transcriptomics. In addition, DG-CDs exhibited an effective healing ability in an MRSA-infected rat keratitis model by exerting antibacterial activity and regulating macrophage polarization from M1 type to M2 type. DG-CDs represent a promising antibacterial nanomedicine with clarified properties and acting mechanism for treating bacterial infection.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082733","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":"The multifunctional role of hydroxyapatite nanoparticles as an emerging tool in tumor therapy.","authors":"Shu Li, Ruinan Yang, Zhengyi Zhao, Mengzhang Xie, Yong Zhou, Qin Zeng, Xiangdong Zhu, Xingdong Zhang","doi":"10.1016/j.actbio.2025.05.019","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.019","url":null,"abstract":"<p><p>Hydroxyapatite nanoparticles (HANPs) are well-known nanomaterials for bone regeneration or repair. In recent years, HANPs have emerged as a potential tool in tumor therapy because of the numerous advantages the nanoparticles offer, including the diverse physicochemical properties, the selective anti-tumor effect, intrinsic immunomodulatory activity, ability to reverse of drug or immune tolerance, allowance of ion substation, good drug-loading capabilities, etc. Notably, the physicochemical properties of the particles, such as size and shape, significantly influence their anti-tumor efficacy. Therefore, to offer a comprehensive understanding of the key properties of HANPs and the involving molecular mechanisms, and provide crucial cues for rational design and development of novel HANPs-based anti-tumor platforms, this review summarizes various synthesis methods of HANPs with controlled physiochemical characteristics and highlights the multifaceted effects such as interactions with tumor cells and immune cells, regulation of the tumor microenvironment (TME), overcoming drug or immune resistance, and their potentials as effective drug carriers. This review also outlines the emerging strategies leveraging HANPs for tumor therapy and diagnostic imaging. At last, we discuss the challenges HANPs face when used for tumor treatment. STATEMENT OF SIGNIFICANCE: Hydroxyapatite nanoparticles (HANPs) have emerged as a promising tool in tumor therapy without compromising biocompatibility. This review highlights the unique and multifaceted features of HANPs in tumor therapy, including the selective induction of tumor cell apoptosis, engagement in immune regulation, reversal of drug or immune resistance, and the loading of diverse anti-tumor drugs or biomaterials. Additionally, this review emphasizes the influence of the intrinsic physicochemical properties of HANPs on their anti-tumor activity, and explores the emerging strategies that leverage HANPs for tumor therapy and diagnostic imaging. In summary, this work aims to provide a comprehensive and deep understanding of the role of HANPs in tumor therapy and is significant for the improved design of HANP-based platforms for tumor therapy.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082735","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":"Collagen fiber density observed in metastatic ovarian cancer promotes tumor cell adhesion.","authors":"Ali Abbaspour, Ana L Martinez Cavazos, Roshan Patel, Ning Yang, Stephanie M McGregor, Erin G Brooks, Kristyn S Masters, Pamela K Kreeger","doi":"10.1016/j.actbio.2025.05.035","DOIUrl":"10.1016/j.actbio.2025.05.035","url":null,"abstract":"<p><p>Collagen type I, a key structural component of the extracellular matrix (ECM), is frequently altered in cancer, with altered fiber organization at the primary tumor site linked to metastasis and poor patient outcomes. Here, we demonstrate that collagen fibers are also altered in metastatic sites such as the omentum of patients with high-grade serous ovarian cancer (HGSOC). Specifically, we observed a significant increase in fiber density, alignment, and width. To determine if the increase in fiber density supports metastasis, we used a semi-interpenetrating methacrylated gelatin (gelMA) network in combination with increasing fibrillar collagen. Cancer cells had significantly increased adhesion as collagen fiber density increased. To determine the responsible mechanisms, we used orthogonal systems to examine 1) the different adhesion peptides exposed in collagen (GFOGER) and gelatin (RGD), and 2) the physical structure of fibers. Cells had minimal response to GFOGER, either alone or in combination with RGD, suggesting that increased adhesion did not result from this collagen-specific interaction. Cell adhesion was significantly higher on electrospun PCL-gelatin fibers compared to flat PCL-gelatin substrates, suggesting that increased cell adhesion resulted from fiber structure. We next investigated the cellular mechanisms involved in increased adhesion on gelMA/coll and found that actin polymerization, but not myosin II contractility, was needed. We further demonstrated that cells on fibrous gels had more robust actin polymerization, and that this resulted in greater adhesion strength. Combined, these results suggest that the increase in collagen fibers with tumor metastasis will support the development of additional metastases. STATEMENT OF SIGNIFICANCE: This work advances the evaluation of the matrisome of the omentum, the most common metastatic site in advanced ovarian cancer by characterizing how collagen fibers change with disease progression. To examine the effect of collagen fibers on metastasis, we utilized a suite of in vitro biomaterials to identify a novel role for collagen fibers in supporting cell adhesion through increased actin dynamics during nascent adhesion formation, which results in increased adhesion strength at later times.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082696","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 photothermal-enhanced thermoelectric nanosheet incorporated with zwitterionic hydrogels for wound repair and bioelectronics.","authors":"Jiamu Xiao, Wei Lu, Ziyi Li, Song Zhang, Xiaolong Zhu, Jiang Yuan, Donglin Gan, Jian Shen, Mingqian Wang","doi":"10.1016/j.actbio.2025.05.033","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.033","url":null,"abstract":"<p><p>The new generation of smart wound dressings aims to encompass sensory restoration capabilities through multi-stimulation rather than merely focusing on skin rebuilding and repair. Wound dressings integrated with real-time measurement of wound motion can improve healing efficiency considerably by providing crucial guidance during the skin regeneration process. Herein, we report a conductive zwitterionic hydrogel dressing with photothermal and thermoelectric properties prepared using a poly(3,4-ethylenedioxythiophene)-modified polydopamine-functionalized bismuth telluride (PEDOT@PBT) sandwich-like nanosheet-incorporated poly(sulfobetaine methacrylate)/silk fibroin (PEDOT@PBT-PSBMA/SF) semi-interpenetrating polymer network hydrogel, which can accelerate chronic wound healing and monitor motion. With the incorporation of PEDOT@PBT nanosheets, the hydrogel exhibits remarkable photothermal and thermoelectric effects, endowing it with broad-spectrum antibacterial properties against Escherichia coli (E. coli, 99.02 %), Staphylococcus aureus (S. aureus, 99.14 %), and methicillin-resistant Staphylococcus aureus (MRSA, 97.70 %). Additionally, the PEDOT@PBT-PSBMA/SF hydrogel can be employed in bioelectronics because of its good conductivity (0.13 S/m). In-vivo experiments show that the PEDOT@PBT-PSBMA/SF hydrogel actively promotes the regeneration of MRSA-infected wounds through immunomodulation, collagen deposition, and vascularization. Consequently, this study presents a promising strategy for the development of next-generation multifunctional hydrogel dressings with considerable potential for application in chronic skin wound therapy and bioelectronics. STATEMENT OF SIGNIFICANCE: Thermoelectric materials are increasingly being incorporated into hydrogels to enhance tissue regeneration. However, improving the thermoelectric efficiency while effectively harnessing the generated electricity for tissue regeneration remains a significant challenge. This study presents a multifunctional hydrogel dressing that integrates advanced photothermal and thermoelectric properties with real-time motion sensing, offering a breakthrough in chronic wound therapy. The PEDOT@PBT-PSBMA/SF hydrogel demonstrates exceptional antibacterial efficacy against E. coli, S. aureus, and MRSA, along with remarkable conductivity suitable for bioelectronic applications. In vivo results highlight its ability to accelerate wound healing through immunomodulation, enhanced collagen deposition, and improved vascularization. In conclusion, this multifunctional hydrogel holds great promise for future development as an integrated platform for diabetic skin wound repair and real-time monitoring.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082692","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":"Effects of iron accumulation and its chelation on oxidative stress in intracortical implants.","authors":"Melissa E Franklin, Jordan L Grant, Grant Lee, Anabel Alvarez Ciara, Cassie Bennett, Serene Mattis, Nicolas Gallardo, Natalie Corrales, Xinyan Tracy Cui, Jeffrey R Capadona, Wolfgang J Streit, Jean-Hubert Olivier, Robert W Keane, W Dalton Dietrich, Juan Pablo de Rivero Vaccari, Abhishek Prasad","doi":"10.1016/j.actbio.2025.05.026","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.026","url":null,"abstract":"<p><p>Long-term reliability of microelectrodes implanted in the cortex is hindered due to the foreign body response that occurs at the electrode-tissue interface. Following implantation, there is disruption of the blood-brain-barrier and vasculature, resulting in activation of immune cells and release of erythrocytes. As a result of hemolysis, erythrocytes degrade to heme and then to free iron. Excess free iron can participate in the Fenton Reaction, producing reactive oxygen species (ROS). Iron-mediated ROS production can contribute to oxidation of lipids, proteins, and DNA, facilitating a hostile environment of oxidative stress leading to oxidative cellular damage, cytotoxicity, and cell death. The objective of this study was to show the iron accumulation and the downstream effects of oxidative stress at the injury site. A 16-channel microelectrode array (MEA) was implanted in the rat somatosensory cortex. Our results indicated significant elevation of NOX complex subunits across timepoints, suggesting sustained oxidative stress. In a separate group of animals, we administered an iron chelator, deferoxamine mesylate (DFX), to evaluate the effects of chelation on iron accumulation, oxidative stress and damage, and neuronal survival. Results indicate that animals with iron chelation showed reduced ferric iron and markers of oxidative stress and damage corresponding with increased expression of neuronal cell bodies and electrophysiological functional performance. In summary, the study reveals the role of iron in mediating oxidative stress and the effects of modulating iron levels using iron chelation at the electrode-tissue interface. STATEMENT OF SIGNIFICANCE: Iron accumulation has been observed in central nervous system injuries and in neurodegenerative diseases such as Alzheimer's and Parkinson's disease. While the role of iron is studied in various neurodegenerative diseases and traumatic brain injury, iron accumulation and its effect on oxidative stress is not known for intracortical implants where there is a persistent injury due to the presence of a foreign device in the brain tissue. The study seeks to understand the effects of iron accumulation on oxidative stress and damage at the electrode-tissue interface in intracortical implants by using iron chelation as a method of modulating iron levels at the interface.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047859","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":"Design and characterization of metallic microfasteners for mechanical adhesion to soft tissues.","authors":"Joseph N Urban, J Scott Malloy, Peyton Fitzgerald, Ernest S Kim, Beau Landis, Anthony Quinnert, Gianna Dafflisio, Sitaram M Emani, Daniel F King, David J D Carter, Corin Williams","doi":"10.1016/j.actbio.2025.05.030","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.030","url":null,"abstract":"<p><p>Suturing by hand remains the gold standard for the manufacturing of bioprosthetic heart valves (BHVs), which is a time- and skill-intensive process to attach tissue valve grafts to stents. Suturing becomes even more challenging for the assembly of small devices, such as pediatric BHVs. Here, we report the development of a sutureless mechanical adhesion to tissue (MANTIS), a microstructured tissue fastening technology that mediates rapid attachment of rigid materials to compliant biological tissues. Following characterization of BHV tissue wall thickness, we designed 4 distinct MANTIS microfastener geometries that were fabricated in stainless steel foils via a photochemical machining process. Bioinspired microfastener designs mimicked flexure of the praying mantis claw to provide enhanced tissue entrapment upon insertion via controlled buckling. Tissue adhesion testing was performed on individual microfasteners and microfastener arrays, with all 4 MANTIS designs outperforming controls across normal, 0° shear, and 180° peel loading orientations. Overall, MANTIS shows promise as a sutureless adhesive technology for integrating mechanically disparate materials such as tissues and medical device surfaces. STATEMENT OF SIGNIFICANCE: Attaching rigid materials to soft biological tissues is a challenging problem. Current options such as sutures, staples, and chemical adhesives often fail to simultaneously achieve strong, permanent coupling in a rapidly deployable and compact form factor. Here, we designed and characterized a family of microfastener designs which can quickly puncture and interlock with connective tissue fibers to form strong adhesion that can resist multi-directional loads. This approach is reminiscent of VELCRO® and its hook-and-loop principle of operation, though our work also incorporates a \"controllable deformation\" functionality inspired by the praying mantis claw. We anticipate MANTIS will provide a valuable new solution for a wide range of applications that require reliable and strong attachment of device surfaces to biological tissues.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033791","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":"Bacterial Extracellular Vesicles: Bridging Pathogen Biology and Therapeutic Innovation.","authors":"Zahra Salehi Moghaddam, Ashkan Dehghan, Saba Halimi, Fatemeh Najafi, Ali Nokhostin, Arya Eimagh Naeini, Iman Akbarzadeh, Qun Ren","doi":"10.1016/j.actbio.2025.05.028","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.028","url":null,"abstract":"<p><p>The main role of bacterial extracellular vesicles (BEVs) has been associated with various processes such as intercellular communication and host-pathogen interactions. This comprehensive review explores the multifaceted functions of BEVs across different biological domains, emphasizing their multifaceted functions as contributors both to disease and as carriers of therapeutic possibilities. We examine the intricate interactions of BEVs within bacterial communities and between bacteria and hosts, their involvement in disease development through cargo delivery mechanisms, and their beneficial impact to microbial ecology. The review places a strong emphasis on BEVs' applications in biomedical sciences, where they are revolutionizing vaccine development, targeted drug delivery, and cancer therapy. By utilizing the inherent properties of BEVs for controlled drug release, targeted antigen delivery, and immune modulation, they offer a promising frontier in precision medicine. In addition, the diagnostic potential of BEVs is explored through their biomarker capabilities, providing valuable insights into disease states and treatment efficacy. Looking forward, this review underscores the challenges and opportunities in translating BEV research to clinical practice, promoting the use of standardized methods in BEV characterization and scaling up production. The diverse abilities of BEVs, ranging from contributing to pathogen virulence to driving therapeutic innovation, highlight their potential as a cornerstone in the future of biomedical advancements. STATEMENT OF SIGNIFICANCE: Bacterial extracellular vesicles (BEVs) are emerging as pivotal players in both pathogenesis and therapeutic innovation. This review explores their dual nature as agents of disease and as promising biomaterials in biomedical applications, and provides a comprehensive survey on their involvement in disease mechanisms and microbial ecology, and their potential in biomedical applications such as vaccine development, targeted drug delivery, cancer therapy and diagnosis. It highlights the complex interactions of BEVs within bacterial communities and between bacteria and hosts. This review also addresses current advancements, challenges, and opportunities in translating BEV research into clinical practice. The insights presented here position BEVs as a cornerstone in the future of biomedical advancements, advocating for standardized methods in BEV characterization and scalable production techniques.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046260","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}