{"title":"Co-assembled polypeptides-adsorbing bridge molecules to enhance macrophage efferocytosis for the resolution of periodontitis inflammation.","authors":"Bang Li, Feng Liang, Ziyang Gao, Xianqing Zhou, Dujuan Zheng, Xinjing Zhang, Mengyao Sun, Xu Yan, Wanjia Li, Yuansong Wang, Xiaoxuan Lu, Leping Wu, Xiaoyu Sun, Hengguo Zhang, Jianguang Xu, Qingqing Wang","doi":"10.1016/j.actbio.2025.08.011","DOIUrl":"10.1016/j.actbio.2025.08.011","url":null,"abstract":"<p><p>Effective removal of apoptotic cells, namely efferocytosis, promotes inflammation resolution of periodontitis and tissue restoration. However, effective treatments to enhance macrophage efferocytosis in periodontitis are still lacking. Co-assembly of distinct building blocks is considered a versatile and effective method of modulating the structure and functionality of supramolecular materials. Herein, a biologically inert amphiphile peptide (PA) (C<sub>16</sub>H<sub>31</sub>ONNCCCCS, PAS) was designed based on a previous amphiphile peptide (C<sub>16</sub>H<sub>31</sub>ONNCCCCRRES(p), PARRES). We described those two peptides' co-assembly in modulating macrophage efferocytosis for periodontitis resolution. The results showed that individual PAS and PARRES co-assemble together and transform the secondary structure from α-helix to β-sheet pattern via hydrogen bonding. Compared with individual PAs, the composite PA adsorbed more \"bridging molecules\" that enhance apoptotic signal binding on macrophages. The enriched \"bridging molecules\" could bind to macrophages on one side via phagocytic receptors and attract the apoptotic cells on the other side, thus promoting efferocytosis. When injected into mice with periodontitis, composite PA promotes inflammation resolution and further promotes periodontal tissue regeneration. This study provided an easily adjustable supermolecular system that enhances efferocytosis for periodontitis and revealed insights into the relationship between physicochemical properties and biological effects of supermolecular materials. STATEMENT OF SIGNIFICANCE: Efferocytosis promotes periodontitis resolution and further tissue restoration. Nevertheless, high-performance therapeutics for promoting efferocytosis are still lacking. Peptides have desirable features, including biocompatibility and sequence-specific secondary structures. A biologically amphiphile peptide (PA) was designed with a similar structure to a previous PA. We described those PAs' co-assembly in modulating efferocytosis for periodontitis resolution. Specifically, those PAs co-assemble together and transform secondary structure from α-helix to β-sheet pattern. The composite PA adsorbs more \"bridging molecules,\" enhancing apoptotic signals binding to macrophages and attracting apoptotic cells for promoting efferocytosis. In vivo, the composite PA promotes periodontitis resolution and regeneration. This study provided an easily adjustable supermolecular system enhancing efferocytosis and revealed insights into the relationship between physicochemical properties and biological effects.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818595","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":"Nanozymes in infected wound therapy: catalytic mechanisms, rational design and combination therapy.","authors":"Shuyi Xing, Bingbing Liu, Luning He, Shuaipeng Feng, Kaisheng Nan, Donghua Di, Yikun Gao, Siling Wang, Yunbo Zhao, Qinfu Zhao","doi":"10.1016/j.actbio.2025.07.065","DOIUrl":"10.1016/j.actbio.2025.07.065","url":null,"abstract":"<p><p>Topics of wound healing have gained increasing attention, and wound healing is a complex dynamic process involving multiple stages and cytokines interactions. The causes of wound formation include physical injury, burns, frostbite resulting in ulcers or abscesses, and chronic diseases such as diabetes. All of these factors can lead to varying degrees of tissue damage. Infectious wound-related diseases are a major public safety concern, affecting the healthy lives of millions of people. Nanozymes, as a new artificial enzyme with the advantages of low cost and good stability, can effectively mimic natural enzyme activity and regulate the wound microenvironment to achieve the alleviation of oxidative stress, lowering of blood glucose, reconstruction of blood vessels, and promotion of infected wound healing. Therapies based on nanozymes and their related strategies have been extensively tapped in wound healing. This review explores the catalytic mechanism of nanozymes for wound treatment and their design directions, which provides readers with ideas for further research on the design of rational nanozymes. In addition, we have systematically explored their synergistic therapy. The clinical potentialities and future trials of nanozymes in boosting antimicrobial wound healing are accentuated in the final part. STATEMENT OF SIGNIFICANCE: Infected wound healing remains a significant challenge in the medical field. Traditional wound treatments are confronted with issues such as antibiotic resistance and limited effectiveness in promoting tissue repair. However, nanozymes, with their unique enzyme-like catalytic activities and nanomaterial properties, have emerged as a promising alternative. Nanozymes can effectively regulate the wound microenvironment to alleviate oxidative stress and inflammation, thereby promoting the healing of infected wounds. In this article, we comprehensively and systematically summarize the latest progress in nanozyme-based wound healing therapies, as well as the strategies for improving current nanozyme-based therapeutic approaches. Moreover, we elaborate on the role of nanozymes in the treatment of infected wounds from multiple perspectives, present examples of the combination of nanozymes with various other wound healing treatment methods, and summarize nanozyme-based delivery systems.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791028","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}
Acta biomaterialiaPub Date : 2025-07-29DOI: 10.1016/j.actbio.2025.07.031
Ying He, Zhaoxu Huang, Jie Liang, Hao Ji, Zhaoxia Pu
{"title":"Synergistic effects of biomaterials and extracellular vesicles in treating myocardial infarction: A systematic review of preclinical studies.","authors":"Ying He, Zhaoxu Huang, Jie Liang, Hao Ji, Zhaoxia Pu","doi":"10.1016/j.actbio.2025.07.031","DOIUrl":"10.1016/j.actbio.2025.07.031","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) combined with biomaterials have shown promise in treating myocardial infarction (MI), with potential to alleviate inflammation, oxidative stress, and apoptosis while improving cardiac function. However, systematic evaluation is needed. This meta-analysis utilized data from PubMed, Web of Science, Scopus, EMBASE, and Ovid medicine from their inception to May 2025. Relevant outcomes were analyzed using GetData Graph Digitizer 2.26 and Review Manager 5.4 software. The quality of studies was assessed using the SYRCLE risk of bias tool and CAMARADES checklist. We measured 12 indicators across cardiac function, fibrosis, apoptosis, and inflammation. The meta-analysis included 33 studies. Compared to EV monotherapy, the combination of EVs with biomaterials significantly improved several cardiac functions and structural parameters. These include: Ejection Fraction (SMD = 1.79; p < 0.00001); Fractional Shortening (SMD = 1.61; p < 0.00001); Myocardial Fibrosis (SMD = -1.83; p = 0.002); Additionally, IL-6 (SMD = -2.55; p = 0.01) and TNF-α (SMD = -1.18; p = 0.01), as well as apoptosis levels (SMD = -3.72; p < 0.0001), were markedly reduced. Among them, intramyocardial injection of MSC-derived EVs combined with hydrogel is the most widely used combination therapy. EVs combined with biomaterials enhance cardiac recovery in MI models with no significant safety issues, highlighting their potential therapeutic benefits. STATEMENT OF SIGNIFICANCE: Myocardial infarction (MI) is one of the leading causes of death and disease burden. Over the past 20 years, extracellular vesicles (EVs) have undergone a remarkable journey and are now poised on the brink of becoming the next generation of cell-free therapeutic tools. Our study aims to quantitatively analyze the efficacy and safety of combining biomaterials with EVs compared to EVs alone in MI through a meta-analytical mapping approach. This is the comprehensive meta-analysis summarizing the effectiveness and safety of various biomaterials combined with EV therapy, highlighting the role of biomaterials in advancing the field. It provides valuable insights for researchers exploring the clinical translation of EV-based therapies.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762638","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}
Acta biomaterialiaPub Date : 2025-07-10DOI: 10.1016/j.actbio.2025.06.052
Luis P Ferreira, Carole Jorge, Matilde R Lagarto, Maria V Monteiro, Iola F Duarte, Vitor M Gaspar, João F Mano
{"title":"Corrigendum to \"Photoacoustic processing of decellularized extracellular matrix for biofabricating living constructs\" [Acta Biomaterialia 183, 2024, 74-88].","authors":"Luis P Ferreira, Carole Jorge, Matilde R Lagarto, Maria V Monteiro, Iola F Duarte, Vitor M Gaspar, João F Mano","doi":"10.1016/j.actbio.2025.06.052","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.06.052","url":null,"abstract":"","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621523","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}
Acta biomaterialiaPub Date : 2025-07-07DOI: 10.1016/j.actbio.2025.06.040
Kai Chen, Xianfeng Lin, Qi Zhang, Jinhu Ni, Jianmin Li, Jian Xiao, Yang Wang, Yiheng Ye, Li Chen, Keke Jin, Lei Chen
{"title":"Corrigendum to \"Decellularized periosteum as a potential biologic scaffold for bone tissue engineering\" [Acta Biomaterialia 2015, 19, 46-55].","authors":"Kai Chen, Xianfeng Lin, Qi Zhang, Jinhu Ni, Jianmin Li, Jian Xiao, Yang Wang, Yiheng Ye, Li Chen, Keke Jin, Lei Chen","doi":"10.1016/j.actbio.2025.06.040","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.06.040","url":null,"abstract":"","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593156","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}
Acta biomaterialiaPub Date : 2025-07-05DOI: 10.1016/j.actbio.2025.07.017
Alexander A Oliver, Jonathan Cortese, Julien Ognard, Daying Dai, Esref A Bayraktar, Yong Hong Ding, Trace A Christensen, Scott I Gamb, Wasantha K Ranatunga, Kent D Carlson, Mukesh K Pandey, Roger J Guillory, Brandon J Tefft, Ramanathan Kadirvel, Dan Dragomir-Daescu, David F Kallmes
{"title":"Magnetic Capture of Autologous Mesenchymal Stem Cells Promotes the Rapid Endothelialization of Peripheral Venous Stents in Rabbits.","authors":"Alexander A Oliver, Jonathan Cortese, Julien Ognard, Daying Dai, Esref A Bayraktar, Yong Hong Ding, Trace A Christensen, Scott I Gamb, Wasantha K Ranatunga, Kent D Carlson, Mukesh K Pandey, Roger J Guillory, Brandon J Tefft, Ramanathan Kadirvel, Dan Dragomir-Daescu, David F Kallmes","doi":"10.1016/j.actbio.2025.07.017","DOIUrl":"10.1016/j.actbio.2025.07.017","url":null,"abstract":"<p><p>The rapid development of an endothelium over venous stents is associated with improved clinical outcomes. In this study, we investigate an approach to rapidly endothelialize venous stents using magnetic cell capture. Autologous mesenchymal stem cells were generated from rabbit adipose tissue and labeled with superparamagnetic iron oxide nanoparticles. Non-magnetic control and magnetic stents were deployed in the opposite external iliac veins of rabbits. The cells were delivered into the stent lumens in the presence of external magnets. Magnetic cell capture and retention, rate of endothelization, and stenosis were evaluated histologically. We found that the cells were capable of being magnetically captured by and adhering to the magnetic stents. Their magnetic capture facilitated the development of an endothelium over the magnetic stents within 3 days. In contrast, no magnetic cell capture was observed on the control stents, and the control stents were completely bare after 3 days. We found no significant difference in stenosis between the control and magnetic stents after 30 days. In conclusion, we demonstrated that autologous adipose derived mesenchymal stem cells labeled with superparamagnetic iron oxide nanoparticles are capable of being magnetically captured to the surface of magnetic stents, improving the rate of endothelialization in a rabbit iliac vein model. STATEMENT OF SIGNIFICANCE: Venous stents are deployed to mechanically open and restore blood flow through diseased, narrowed veins. Bare metal initially contacts blood, which may provoke thrombosis and neointimal hyperplasia leading to restenosis. Current drug‑eluting stents curb smooth muscle proliferation but delay endothelial healing, while antibody‑coated endothelial progenitor cell‑capturing stents accelerate healing but require permanent, expensive bioactive coatings. We studied autologous mesenchymal stem cells tagged with superparamagnetic iron‑oxide nanoparticles, magnetically drawn onto ferromagnetic stents by an external field. In a rabbit iliac vein model, this one‑time magnetic seeding significantly increased the rate of endothelialization on magnetic stents compared to non‑magnetic controls. This approach offers a mechanically simple, coating‑free route to improve venous stenting outcomes.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585841","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}
Acta biomaterialiaPub Date : 2025-06-27DOI: 10.1016/j.actbio.2025.06.055
Hangqi Luo, Christopher W Anderson, Xin Li, Yinsheng Lu, Marie Hoareau, Qinzhe Xing, Saba Fooladi, Yufeng Liu, Zhen Xu, Jinkyu Park, Meghan E Fallon, Jordan Thomas, Peter J Gruber, Robert W Elder, Michael Mak, Muhammad Riaz, Stuart G Campbell, Yibing Qyang
{"title":"Advanced tissue-engineered pulsatile conduit using human induced pluripotent stem cell-derived cardiomyocytes.","authors":"Hangqi Luo, Christopher W Anderson, Xin Li, Yinsheng Lu, Marie Hoareau, Qinzhe Xing, Saba Fooladi, Yufeng Liu, Zhen Xu, Jinkyu Park, Meghan E Fallon, Jordan Thomas, Peter J Gruber, Robert W Elder, Michael Mak, Muhammad Riaz, Stuart G Campbell, Yibing Qyang","doi":"10.1016/j.actbio.2025.06.055","DOIUrl":"10.1016/j.actbio.2025.06.055","url":null,"abstract":"<p><p>Single ventricle congenital heart defects (SVCHDs) are life-threatening defects that can lead to severe circulation issues and increased stress on the heart. Without prompt treatment, these defects can prove fatal in infancy. Fontan surgery is a conventional treatment for SVCHDs, which reroutes oxygen-poor blood directly to the lungs, bypassing the non-functioning ventricle. This procedure, however, can lead to circulation inefficiencies due to the absence of a natural, functional ventricle to pump blood to the pulmonary circulation. To address this issue, our team previously developed a tissue-engineered pulsatile conduit (TEPC) by wrapping engineered heart tissues (EHTs) derived from human induced pluripotent stem cell-derived cardiomyocytes (hiPSCCMs) around decellularized human umbilical artery (dHUA). This conduit has demonstrated the ability to produce a luminal pressure of 0.68 mmHg from spontaneous beating, which under 2 Hz electrical stimulation, increases to 0.83 mmHg. This offers a promising modular TEPC design that has the potential to provide active pumping function to the pulmonary circulation. We have since significantly optimized our approach by providing the conduit with electrical pacing training and an additional layer of EHT. These two enhancements have achieved markedly greater contractile productivity, where the spontaneous pressure generation reached 0.96 mmHg and the stimulated luminal pressure generation attained 1.87 mmHg with 2 Hz pacing. Our studies thus underscore the effectiveness of these TEPC design modifications, marking significant progress in the ongoing effort to improve treatments for patients with SVCHDs. STATEMENT OF SIGNIFICANCE: Single ventricle congenital heart defects (SVCHDs) are a life-threatening disorder, leading to severe circulation issues and heart failure. The Fontan procedure reroutes blood to the lung but lacks active pumping required for efficient circulation, often causing long-term complications. To address this challenge, we developed a tissue-engineered pulsatile conduit (TEPC) using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and decellularized human umbilical artery (dHUA) scaffolds. Our optimized design, with electrical pacing and enhanced engineered heart tissue (EHT) approaches, significantly increased luminal pressure development (up to 1.87 mmHg at 2 Hz frequency), offering a promising solution to improve outcomes for SVCHD patients.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12338880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta biomaterialiaPub Date : 2025-06-26DOI: 10.1016/j.actbio.2025.06.046
Vicky Y Wang, Yang Zhu, Kimberly A Spaulding, Morgan Pfaff, Gabriel Neiman, Kiyoaki Takaba, Ningxin Chen, Kavita Parekh, Abdallah Hasaballa, Henrik Haraldsson, Anthony Baker, David Saloner, Arthur W Wallace, Nicolas P Ziats, Kevin E Healy, Mark B Ratcliffe
{"title":"NIPAAm-co-PEG4000 thermoresponsive hydrogel with ROS scavenging properties improves in vivo border zone contractility and reduces myocardial remodeling in sheep after MI.","authors":"Vicky Y Wang, Yang Zhu, Kimberly A Spaulding, Morgan Pfaff, Gabriel Neiman, Kiyoaki Takaba, Ningxin Chen, Kavita Parekh, Abdallah Hasaballa, Henrik Haraldsson, Anthony Baker, David Saloner, Arthur W Wallace, Nicolas P Ziats, Kevin E Healy, Mark B Ratcliffe","doi":"10.1016/j.actbio.2025.06.046","DOIUrl":"10.1016/j.actbio.2025.06.046","url":null,"abstract":"<p><p>Decreased contractility of the border zone (BZ) myocardium after MI is associated with oxidative stress mediated contractile protein dysfunction. We hypothesized that injection of a thermo-responsive hydrogel with enhanced reactive oxygen species (ROS) scavenging would improve the in vivo contractility of BZ myocardium. To that end, 14 adult male sheep underwent MI. Of those, 6 sheep had a comb-like copolymer synthesized from N-isopropyl acrylamide and 4000 MW methoxy poly(ethylene glycol) methacrylate (NIPAAm-co-PEG4000) injected into the MI zone (MI+Hydrogel). In vivo cardiac magnetic resonance imaging (CMR), including cine DENSE (Displacement encoding with stimulated echoes), was performed before and 6 weeks after MI to measure LV geometry and regional displacement. Tissue ROS and in vitro muscle strip developed force were measured in the BZ and remote regions. Compared to the MI group 6 weeks after MI, MI+Hydrogel exhibited: 1) a reduction in indexed LV end-diastolic (ED) volume; 2) an increase in average wall thickness at ED; and, 3) an increase in average peak circumferential strain in the BZ near the MI border. ROS was significantly lower in the MI+Hydrogel group and muscle strip developed force was significantly increased in the BZ. These observations support the hypothesis that injection of a hydrogel with enhanced ROS scavenging improves in vivo BZ contractility and attenuates ventricular remodeling after MI in sheep. STATEMENT OF SIGNIFICANCE: This work supports our hypothesis that intramyocardial injection of hydrogel with enhanced reactive oxygen species (ROS) scavenging improves in vivo contractility of myocardium bordering the infarct and attenuates pathological ventricular remodeling after myocardial infarction. We believe this multidisciplinary research would be of interest by researchers in the fields of hydrogel biomaterials, finite element biomechanical analysis, and cardiovascular diseases.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531602","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":"Anti-inflammatory itaconate-loaded, cell-adhesive peptide-conjugated artificial small diameter vascular grafts for blood vessel regeneration.","authors":"Yu Gao, Yuwei Li, Nan Jiang, Rui Gao, Yushan Zhang, Zujian Feng, Chuangnian Zhang, Lianyong Wang, Weiwei Wang, Deling Kong, Pingsheng Huang","doi":"10.1016/j.actbio.2025.06.034","DOIUrl":"10.1016/j.actbio.2025.06.034","url":null,"abstract":"<p><p>The adverse remodeling is a major cause of the low patency rate of artificial small-diameter vascular grafts (SDVGs), preventing clinical application in vascular disease treatment. To inhibit intimal hyperplasia and achieve rapid endothelialization after implantation, we designed PLCL/OI@REDV grafts composed of poly (l-lactide-co-ε-caprolactone) (PLCL) electrospinning tubes loaded with anti-inflammatory 4-octyl itaconate (OI) and coated with cell-adhesive REDV peptide. PLCL/OI@REDV grafts showed a micro-scale fibrous crosslinked structure and a burst pressure higher than 1600 mmHg. Then, PLCL/OI@REDV membranes were verified to inhibit the smooth muscle cell (SMC) proliferation via the release of OI and to promote the adhesion and proliferation of endothelial cells (ECs) due to REDV modification, contributing to the competitive growth of ECs. Furthermore, it was confirmed that OI showed significant suppression of M1 macrophage polarization, thereby reducing the production of inflammatory factors and reactive oxygen species, which in turn maintained the viability and function of ECs. Subcutaneous implantation in rats demonstrated that PLCL/OI@REDV membranes elicited lower levels of inflammatory and fibrotic reactions than PLCL membranes. In rat abdominal aorta replacement models, compared with PLCL grafts, PLCL/OI@REDV grafts were found to down-regulate the M1 macrophage expression, inhibit excessive SMC proliferation, and promote endothelialization, collectively improving vascular regeneration and patency. In summary, PLCL/OI@REDV graft represents a promising artificial vascular graft with endogenous regeneration ability. STATEMENT OF SIGNIFICANCE: Small-diameter artificial vascular grafts (SDVGs) hold broad application prospects in clinical hemodialysis, and peripheral or coronary artery bypass grafting. However, they are faced with a high risk of thrombosis and stenosis caused by inflammation, intimal hyperplasia and slow endothelialization. In this study, we prepared a SDVG, PLCL/OI@REDV, composed of poly (l-lactide-co-ε-caprolactone) (PLCL) electrospinning tube loaded with anti-inflammatory and anti-fibrotic 4-octyl itaconate, and coated with cell-adhesive peptide REDV. PLCL/OI@REDV collectively reduced inflammation by suppressing M1 macrophage polarization, inhibited intimal hyperplasia by decreasing the excessive smooth muscle cell proliferation, and facilitated endothelialization via improving endothelial cell adhesion and proliferation, thus increasing patency rate. Therefore, PLCL/OI@REDV is a promising SDVG with endogenous regenerative ability.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340771","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}