Acta biomaterialia最新文献

{"title":"Polymer conjugation benefits proteins beyond simply extended half-life.","authors":"Lingli Cao, Chaoxin Yang, Zhipeng Zeng","doi":"10.1016/j.actbio.2025.05.053","DOIUrl":"10.1016/j.actbio.2025.05.053","url":null,"abstract":"<p><p>Polymer conjugation is well known to extend the half-life of proteins in the bloodstream. The resulting protein-polymer conjugates have gained tremendous success due to this benefit, most prominently with the numerous PEGylated protein therapeutics that have been approved by the Food and Drug Administration (FDA). Prolonged half-life of protein therapeutics is usually accompanied by improved therapeutic outcome and patient compliance. However, simply extending the half-life of proteins is no longer sufficient to address the different therapeutic requirements of different diseases. Modern medicine has placed higher functional demands for protein therapeutics, such as biological barrier permeability, lower off-target effects, and higher biosafety. Indeed, the benefits of polymer conjugation for proteins have been greatly expanded beyond just extending the half-life, such as improving therapeutic index, facilitating intracellular delivery, remodeling biodistribution, penetrating the blood-brain barrier, and promoting oral absorption. Therefore, this short review will aim to systematically reveal the benefits of polymer conjugation for proteins at molecular, nanoscale, cellular, tissue, organ, and organ system level. The challenge and new direction for the development and clinical translation of protein-polymer conjugates are also covered. STATEMENT OF SIGNIFICANCE: Since the concept was pioneered by Frank Davis in the late 1960s, protein-polymer conjugates have gained tremendous success. Therapeutics based on protein-polymer conjugates have longer half-lives in the bloodstream compared to their native forms, which reduces dosing frequency and greatly enhances patient compliance. Indeed, beyond improved pharmacokinetic, protein-polymer conjugates have demonstrated multifaceted biological benefits, such as facilitating intracellular delivery, penetrating tissue barriers, remodeling biodistribution, and promoting oral absorption. This review aims to systematically reveal the benefits of polymer conjugation for proteins at the molecular, nanoscale, cellular, tissue, organ, and organ system level. Such comprehensive understanding will not only broaden the impact of protein-polymer conjugates, but also enable researchers to advance their development in the desired direction.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144872","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":"Natural regeneration-inspired sequential delivery of synergistic growth factors for structural and functional endometrial regeneration.","authors":"Cheng Zhang, Chengcheng Zhu, Xiao Chen, Xuzhi Chen, Di Zhang, Huafei Zhao, Junwen Zhang, Yu Zhang, Wanwan Xu, Xiaofeng Zhao, Yingying Hu, Wei Wei, Jian Xu, Yu Li, Bingbing Wu","doi":"10.1016/j.actbio.2025.05.050","DOIUrl":"10.1016/j.actbio.2025.05.050","url":null,"abstract":"<p><p>Large-scale deep endometrial injury has a serious impact on the reproductive health of women, necessitating the development of novel therapeutic approaches. Treatment strategies using single factor may not perfectly match the intricate and dynamic process of endometrial regeneration. In light of the sequential progression of vascularization and endometrial remodeling observed during the regeneration of injured endometrium, a dual growth factor sequential delivery system is prepared by loading IGF-1 onto hydrogel microspheres and blending with an outer bulk hydrogel containing VEGF. The controlled degradation of hydrogel facilitates the sequential release of the two factors, thereby fostering the vascularization, migration and proliferation of endometrial cells in vitro. Animal experiments have proved that the hydrogel system can promote the regeneration of endometrial structure through vascular remodeling, glandular regeneration, and proliferation of endometrial cells, and simultaneously improve the rate of embryo implantation and live birth, which further indicates the functional reconstruction of the injured endometrium. Consequently, drawing inspiration from the sequential process of endometrial regeneration, this study provides innovative strategies for structural and functional restoration of the endometrium. STATEMENT OF SIGNIFICANCE: This research presents an innovative approach to the treatment of injured endometrium through a sequential dual growth factor delivery system. The system involves the incorporation of IGF-1 onto hydrogel microspheres, which are subsequently embedded within a GelMA hydrogel matrix containing VEGF. Unlike conventional hydrogel-based therapeutic strategies that involve the loading of growth factors, the developed delivery system is engineered in accordance with the vascularization and endometrial remodeling processes inherent to the regeneration of injured endometrial tissue. It facilitates the initial release of VEGF to stimulate the formation of blood vessels, followed by a gradual release of IGF-1 during the intermediate phase of endometrial regeneration to promote tissue remodeling. Pre-clinical animal studies have demonstrated that this innovative delivery strategy effectively restores the structure and function of the endometrium, suggesting significant potential for clinical application.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144869","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":"Programmed drug delivering Janus hydrogel adapted to the spatio-temporal therapeutic window for Achilles tendon repair.","authors":"Zekun Zhou, Xiaoduo Tang, Dongxu Huang, Miao Chen, Xin Wei, Yongxin Zhan, Meijun Jiang, Xiang Chen, Xingyao Cui, Junhu Zhang, Xu Gong","doi":"10.1016/j.actbio.2025.05.052","DOIUrl":"10.1016/j.actbio.2025.05.052","url":null,"abstract":"<p><p>Peritendinous adhesion formation and tendon re-rupture are prevalent clinical complications following tendon repair surgery. The key to reducing adhesions and enhancing the biomechanical strength of injured tendons lies in suppressing inflammation and extrinsic fibroblast activation while promoting intrinsic tenocyte proliferation. However, as tenocytes are inherently a type of fibroblast, it remains challenging for a single drug to reduce adhesion and improve tendon strength simultaneously. To address this challenge, a Janus hydrogel was designed for spatiotemporal programmed drug delivery specifically tailored to Achilles tendon repair. The outer layer of the Janus hydrogel rapidly releases melatonin (MT) via poly(N-acryloyl alaninamide) (PNAAA), effectively suppressing inflammation and extrinsic fibroblast activation. The inner layer gel, formed by thiol-modified gelatin (GelSH) and norbornene-modified hyaluronic acid (HANB), incorporates protein-binding AAc-NHS and gradually releases platelet-derived growth factor-BB (PDGF-BB), thereby promoting tenocyte proliferation. In the rat Achilles tendon injury model, the spatiotemporal programmed drug delivery Janus hydrogel successfully reduced adhesion while enhancing tendon healing strength. This work promoted Achilles tendon repair by meeting the distinct spatiotemporal therapeutic needs. STATEMENT OF SIGNIFICANCE: Melatonin may inhibit fibroblast proliferation and differentiation via the PI3K/AKT pathway, whereas PDGF-BB promotes tenocyte proliferation and differentiation through the same pathway. Consequently, the effects of these two drugs on fibroblasts and tenocytes may be conflicting. In this study, the programmed drug delivery Janus hydrogel was designed to match the different stages of tendon repair and achieved staggered release of melatonin and PDGF-BB. Melatonin@PNAAA primarily targets the extrinsic healing pathway, focusing on inflammatory cells during the inflammatory phase and fibroblasts during the proliferative phase. PDGF-BB@SHNB mainly targets intrinsic healing pathway, focusing on tenocytes during the proliferative phase and collagen synthesis during the remodeling phase. This spatiotemporal delivery system alleviates adhesion while promoting tendon healing.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144917","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":"Exoskeletal cuticle proteins enable Drosophila locomotion.","authors":"Maximilian Göpfert, Jing Yang, Dhyeykumar Rabadiya, Dietmar Riedel, Bernard Moussian, Matthias Behr","doi":"10.1016/j.actbio.2025.05.046","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.046","url":null,"abstract":"<p><p>Exo- and Endoskeleton function enables muscle-mediated locomotion in animals. In mammals, the defective protein matrix of bones found in systematic skeletal disorders such as osteoporosis causes fractures and severe skeletal deformations under high muscle tension. We identified an analogous mechanism for integrating muscle-mediated tension into the apical extracellular matrix (aECM) of the invertebrate body wall exoskeleton. Obstructor chitin-binding proteins, the chitin deacetylases, Chitinases, and the matrix-protecting proteins Knickkopf and Retroactive are epidermally expressed during late embryogenesis. Their control of forming epidermal chitinous structures protects the exoskeletal aECM from collapsing when embryos start moving and hatch as larvae. In a larval locomotion assay we tested the function of these cuticle related genes. Gene mutations and knockdowns caused changes in normal movement behavior and lower the speed of larvae. Moreover, we found that the transmembrane Zona Pellucida domain protein Piopio provides the adhesion between the epidermal apical membrane and the overlaying chitinous aECM in a matriptase-dependent manner. A failure of Pio and chitin-associated proteins leads to exoskeletal deformations and detachment from the epidermal membrane, destabilizing muscle forces and impairing larval mobility. Our data identifies a protein network that transforms the chitinous aECM into a stable exoskeleton that directly resists muscle impact at epidermal tendon cells, thereby serving locomotion. Demonstrating the importance of these proteins in producing aECM as a three-dimensional cuticular scaffold for exoskeletal function opens up opportunities for the development of biomimetic applications of synthetic materials. STATEMENT OF SIGNIFICANCE: Chitin-based materials include hydrogels, microcapsules, membranous films, sponges, tubes, and various porous structures. In nature, chitin structures form cuticles, which serves as the exoskeleton of arthropods. Using Drosophila melanogaster, we have performed systematic analyses to identify the proteins and enzymes that organize chitin polymers in 3D structures of the cuticle exoskeleton. Three-dimensional laser-scanning and ultrastructural electron microscopy revealed deformations of the cuticle structure, lack of cellular cuticle adhesion, and overall changes in the flexibility of the chitin-based material, leading to insufficient function of the exoskeleton. Components such as the identified proteins and enzymes, which play a unique role in the organization of the chitin fibers and the formation of the exoskeleton, offer suitable materials for tissue engineering for biomimetic applications.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144866","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":"Effect of electrical stimulation generated by self-powered systems for tissue repair.","authors":"Mengnan Chai, Yufan Li, Yubao Li, Yi Zuo, Jidong Li","doi":"10.1016/j.actbio.2025.05.047","DOIUrl":"10.1016/j.actbio.2025.05.047","url":null,"abstract":"<p><p>Bioelectricity plays an important role in tissue repair. Nanogenerators can harvest biomechanical energy and convert it into electrical signals, producing electrical stimulation (ES) for diverse biomedical applications including sensing, tissue repair, cardiac pacing, etc. This review focuses on the overview of the single or multifunctional role of ES generated by self-powered nanogenerators in bone and tendon, nerve, skin, and myocardial tissue repair. Particularly, to elucidate the differential cellular responses and effects on endogenous electric fields between conventional repair and ES-enhanced tissue regeneration, the possible mechanisms by which ES promotes repair in different tissues are summarized. Eventually, the ES parameters and the matching between the type of ES produced by the nanogenerator and the practical application scenario of biological tissue are discussed. The main challenges and future perspectives of nanogenerators in tissue therapy are also proposed, expecting to promote the development of this emerging restoration method. STATEMENT OF SIGNIFICANCE: As miniature devices for tissue repair, self-powered nanogenerators can achieve the ambitious goal of self-supplying energy and efficient tissue repair. This review article details the electrical stimulation generated by self-powered nanogenerators in different tissue repair by simulating and augmenting endogenous bioelectrical signals. Introducing the classification and mechanisms of nanogenerators and reviewing the influence of the electrical stimulation and electric field in bone and tendon, nerve, skin, and myocardial tissue repair. Notably, the possible mechanisms by which electrical stimulation acts on different tissues are concluded. Lastly, the match between types of nanogenerators and different tissues is proposed, and the main challenges and perspectives of nanogenerators in tissue therapy are also discussed.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133339","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":"Corrigendum to \"Nanoengineered injectable hydrogels for wound healing application\" [Acta Biomaterialia 2018, 70, 35-47].","authors":"Giriraj Lokhande, James K Carrow, Teena Thakur, Janet R Xavier, Madasamy Parani, Kayla J Bayless, Akhilesh K Gaharwar","doi":"10.1016/j.actbio.2025.05.005","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.005","url":null,"abstract":"","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111507","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":"Corrigendum to \"AKR1B10 (Aldo-keto reductase family 1 B10) promotes brain metastasis of lung cancer cells in a multi-organ microfluidic chip model\" [Acta Biomaterialia 2019, 91, 195-208].","authors":"Wenwen Liu, Jing Song, Xiaohui Du, Yang Zhou, Yang Li, Rui Li, Li Lyu, Yeting He, Junxia Hao, Jing Ben, Wei Wang, Haibin Shi, Qi Wang","doi":"10.1016/j.actbio.2025.05.004","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.004","url":null,"abstract":"","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096220","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":"Sustained ROS Scavenging and Pericellular Oxygenation by Lignin Composites Rescue HIF-1α and VEGF Levels to Improve Diabetic Wound Neovascularization and Healing.","authors":"Jangwook P Jung, Oluyinka O Olutoye, Tanuj J Prajati, Olivia S Jung, Lane D Yutzy, Kenny L Nguyen, Stephen W Wheat, JoAnne Huang, Benjamin W Padon, Fayiz Faruk, Sonya S Keswani, Phillip Kogan, Aditya Kaul, Ling Yu, Hui Li, Shiyanth Thevasagayampillai, Mary E Guerra, Walker D Short, Preethi H Gunaratne, Swathi Balaji","doi":"10.1016/j.actbio.2025.04.047","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.047","url":null,"abstract":"<p><p>Although delayed wound healing is an important clinical complication in diabetic patients, few targeted treatments are available, and it remains a challenge to promote diabetic wound healing. Impaired neovascularization is one of the prime characteristics of the diabetic phenotype of delayed wound healing. Additionally, increased levels of reactive oxygen species (ROS) and chronic low-grade inflammation and hypoxia are associated with diabetes, which disrupts mechanisms of wound healing. We developed lignosulfonate composites with several wound healing properties, including sustained oxygen release through calcium peroxide nanoparticles and reactive oxygen species and free radical scavenging by thiolated lignosulfonate nanoparticles. Sustained release of oxygen and ROS-scavenging by these composites promoted endothelial cell (EC) branching and characteristic capillary-like network formation under high glucose conditions in vitro. Gene co-expression network analysis of RNA-sequencing results from ECs cultured on lignin composites showed regulation of inflammatory pathways, alongside the regulation of angiogenic hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth (VEGF) factor pathways. In vivo, lignosulfonate composite treatment promoted VEGF expression and angiogenesis in full thickness skin wounds in diabetic mice, a model of delayed wound healing. Treatment of diabetic wounds with lignosulfonate composites also promoted faster epithelial gap closure and increased granulation tissue deposition by day 7 post-wounding, with a higher presence of pro-healing type macrophages. Our findings demonstrate that lignosulfonate composites promote diabetic wound healing without requiring additional drugs. This highlights the potential of functionalized lignosulfonate for wound healing applications that require balanced antioxidation and controlled oxygen release. STATEMENT OF SIGNIFICANCE: The lignosulfonate composites developed in this study offer a promising solution for delayed wound healing in diabetic patients. By effectively addressing key factors contributing to the multifaceted pathophysiology of the diabetic wounds, including impaired neovascularization, increased ROS levels, and chronic inflammation and wound proteolysis, these composites demonstrate significant potential for promoting wound repair and reducing the complications associated with diabetic wounds. The unique combination of pro-angiogenic, oxygen-releasing, ECM remodeling and antioxidant properties in these lignosulfonate-based materials highlights their potential as a valuable therapeutic option, providing a multi-pronged approach to diabetic wound healing without the need for additional drugs.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038171","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":"Biomechanical insights into the development and optimization of small-diameter vascular grafts.","authors":"Xili Ding, Dongyu Sha, Kaixin Sun, Yubo Fan","doi":"10.1016/j.actbio.2025.04.028","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.028","url":null,"abstract":"<p><p>Small-diameter vascular grafts (SDVGs; inner diameter ≤6 mm) offer transformative potential for treating cardiovascular diseases, yet their clinical application remains limited due to high rates of complications such as acute thrombosis and intimal hyperplasia (IH), which compromise long-term patency. While advancements in biological and material science have driven progress, the critical role of biomechanical factors-such as hemodynamic forces and mechanical mismatch-in graft failure is often overlooked. This review presents insights from recent clinical trials of SDVG products and summarizes biomechanical contributors to failure, including disturbed flow patterns, mechanical mismatch, and insufficient mechanical strength. We outline essential mechanical performance criteria (e.g., compliance, burst pressure) and evaluation methodologies to assess SDVG performance. Furthermore, we present optimization strategies based on biomechanical principles: (1) graft morphological design optimization to improve hemodynamic stability, (2) structural, material, and fabrication innovations to achieve compliance matching with native arteries, and (3) biomimetic approaches to mimic vascular tissue and promote endothelialization. By systematically addressing these biomechanical challenges, next-generation SDVGs may achieve superior patency, accelerating their clinical translation. This review highlights the necessity of considering biomechanical compatibility in SDVG development, thereby providing initial insights for the clinical translation of SDVG. STATEMENT OF SIGNIFICANCE: Small-diameter vascular grafts (SDVGs) offer transformative potential for cardiovascular disease treatment but face clinical limitations. While significant progress has been made in biological and material innovations, the critical role of biomechanical factors in graft failure has often been underestimated. This review highlights the importance of biomechanical compatibility in SDVG design and performance, emphasizing the need to address disturbed flow patterns, mechanical mismatch, and inadequate mechanical strength. By proposing optimization strategies based on biomechanical principles, such as graft morphological design, compliance matching, and biomimetic approaches, this work provides a roadmap for developing next-generation SDVGs with improved patency. These advancements have the potential to overcome current limitations, accelerate clinical translation, ultimately benefiting patients worldwide.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014216","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":"Magnetic capture of blood outgrowth endothelial cells to the luminal surface of magnetizable stent-grafts promotes healing in a porcine pseudoaneurysm model.","authors":"Alexander A Oliver, Kent D Carlson, Colin Price, Karolina Banaskiewicz, Amy Benike, Daying Dai, Robert A Brown, Gurpreet S Sandhu, Ramanathan Kadirvel, Roger J Guillory, Brandon J Tefft, David F Kallmes, Jonathan J Morrison, Dan Dragomir-Daescu","doi":"10.1016/j.actbio.2025.03.040","DOIUrl":"10.1016/j.actbio.2025.03.040","url":null,"abstract":"<p><p>Stent-grafts are endovascular devices used to treat many arterial conditions including carotid artery pseudoaneurysms. Stent-grafts are composed of a metal stent backbone covered by a synthetic membrane to form a conduit. Their deployment results in a large surface area of synthetic material in contact with blood, which increases the risk of thrombosis and occlusion of the device. The more rapidly the blood contacting surface becomes covered with an endothelium, acting as a barrier between the device and blood flow, the lower the risk of these complications. One approach to promote the rapid endothelialization of a stent-graft is with magnetic cell capture. In the current work, we develop magnetizable stent-grafts and generate autologous blood outgrowth endothelial cells from peripheral blood. The cells are labeled with superparamagnetic iron oxide nanoparticles to impart magnetic properties. The ability of the magnetic stent-grafts to occlude pseudoaneurysms and magnetically capture delivered cells is investigated relative to non-magnetic stent-graft controls in a porcine carotid pseudoaneurysm model. We demonstrated that at the study endpoints, the control and magnetic stent-grafts had occluded 7/9 and 9/9 of the pseudoaneurysms, respectively. Histological analysis demonstrated a higher degree of magnetic cell capture, endothelialization, and luminal tissue coverage in the magnetic stent-grafts compared to their non-magnetic controls. At the study endpoints, 2/9 control stent-grafts had completely thrombosed while 0/9 magnetic stent-grafts had. In conclusion, the magnetic stent-grafts facilitated the magnetic capture of blood outgrowth endothelial cells, which appeared to improve biological outcomes relative to non-magnetic stent-graft controls. STATEMENT OF SIGNIFICANCE: Stent-grafts are devices deployed in the arteries to restore blood flow. They are composed of a stent backbone covered by a membrane of synthetic material to form a conduit. Their deployment results in a large surface area of synthetic material in contact with blood. This increases the risk of thrombosis and the narrowing and occlusion of the device. The more rapidly the blood contacting surface becomes covered with an endothelium, acting as a barrier between the device and blood flow, the lower the risk of these complications. In the current study, we investigate an approach to magnetically adhere endothelial cells to the surface of magnetizable stent-grafts to promote the rapid development of an endothelium in a pig model.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694082","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}