Acta biomaterialia最新文献

{"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":"Quantum sensing to monitor changes in free radical generation by intracellular vesicles of polarized macrophages.","authors":"Aldona Mzyk, Claudia Reyes-San-Martin, Yasemin Doğan, Willem Woudstra, Yue Zhang, Ezgi Yilmaz, Reinier Bron, Willy de Haan-Visser, Kirstine Berg-Sorensen, Romana Schirhagl","doi":"10.1016/j.actbio.2025.04.024","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.04.024","url":null,"abstract":"<p><p>Macrophages are immune cells crucial in clearing our tissues from bacteria, viruses, dying cells, cell debris and other waste products. They also regulate inflammation by differentiating from non-activated (M0) cells into macrophages that initiate inflammation (pro-inflammatory macrophages, M1), or resolve inflammation (anti-inflammatory macrophages, M2). One of their key functions is to ingest pathogens within vesicles where they are degraded. The production of free radical (FR) plays an important role in this degradation process but also in macrophage differentiation and signaling. Here we used diamond-based quantum sensing to track free radical changes in vesicles with nanoscale resolution. We further followed the oxidative stress status, through free radical measurement during the macrophage activation process. We found that the three macrophage subtypes differed significantly in free radical generation in their vesicles. Additionally, we showed that the FR generation evolves over time in the different subtypes. We observed a 50 % increase in radical production in M0 after 24 h compared to the T1 values measured after 4 h of cell culture, a decrease in M1 and constant radical levels in M2 macrophages. STATEMENT OF SIGNIFICANCE: Here we use quantum sensing for the first time to investigate the role that free radicals play in immune cells when they differentiate to fulfill their functions in the immune system. We were able to measure free radical generation specifically in vesicles while the macrophages differentiated.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059467","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 biomimetic nanofiber composite hydrogel with tissue adhesion, self-healing and antibacterial ability for infected wound healing.","authors":"Yinghao Tian, Xiaogang Bao, Shunmin Wang, Chen Tang, Nianqi Wu, Guifei Li, Kaixuan Ren, Jingbo Yin, Shifeng Yan, Guohua Xu","doi":"10.1016/j.actbio.2025.04.002","DOIUrl":"10.1016/j.actbio.2025.04.002","url":null,"abstract":"<p><p>Skin injuries represent a significant clinical challenge, as conventional dressings frequently induce secondary trauma and microbial infiltration due to suboptimal barrier properties, ultimately delaying tissue repair. Ideal wound dressings should not only replicate the structure of native skin tissue but also create an environment conducive to cell viability. In this study, an injectable nanofiber composite self-healing hydrogel was developed for treating infected wounds. The antimicrobial properties of the hydrogel were achieved through the adsorption of branched polyethyleneimine (PEI) on gelatin fibers, while its self-healing capabilities were enhanced via Schiff base reactions and its tissue adhesion was strengthened by the incorporation of dopamine. Results demonstrated that the hydrogel exhibited strong biocompatibility and antimicrobial activity, promoted macrophage polarization towards the M2 phenotype, effectively suppressed inflammation, and facilitated wound healing in an infected wound model. STATEMENT OF SIGNIFICANCE: Wound infections pose a significant clinical challenge, often impeding healing and, in severe cases, leading to ulceration or life-threatening complications. In this study, a gelatin nanofiber composite hydrogel (PGF@ALG/PLGA hydrogel) functionalized with branched polyethyleneimine (PEI) was developed to address infected wounds through a biomimetic structure and enhanced pro-healing properties. The gelatin nanofibers within the hydrogel matrix facilitated electrostatic immobilization of PEI, effectively mitigating its inherent cytotoxicity by restricting free cationic charge exposure while ensuring localized surface enrichment. The resulting hydrogel exhibited robust tissue adhesion and autonomous self-healing capability. In infected wound models, the PEI-modified nanofibers within PGF@ALG/PLGA hydrogels demonstrated obvious antibacterial efficacy and promoted macrophage polarization to the M2 phenotype, synergistically accelerating the transition from the inflammatory phase to tissue regeneration. These findings underscore the therapeutic potential of PGF@ALG/PLGA hydrogel as a multifunctional platform for managing chronic infected wounds.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788977","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}

{"title":"Construction of small-diameter vascular grafts by electrospun zwitterionic diselenide-containing poly(ester urethane)urea with enhanced endothelialization.","authors":"Liang Yuan, Yong Gao, Qing Wang, Kongying Zhu, Lixia Ren, Xiaoyan Yuan","doi":"10.1016/j.actbio.2025.02.031","DOIUrl":"10.1016/j.actbio.2025.02.031","url":null,"abstract":"<p><p>Cardiovascular diseases are the leading threat to human health. However, as an essential tool of vascular transplantation, small-diameter vascular grafts are still needed to intensify in rapid endothelialization and enhanced elasticity for vascular reconstruction. Herein, a series of zwitterionic diselenide-containing poly(ester urethane)ureas (zSePEUUs) are synthesized through modulation of the molar ratios of sulfobetaine-diol (SB-diol) and poly(ε-caprolactone)-diol (PCL-diol) (SB-diol/PCL-diol=1/0∼0/1) as diol components, along with selenocystamine and 1,4-butanediamine (7:3) as chain extenders. At the equal amount of SB-diol and PCL-diol, the synthesized zSePEUU polymer with enhanced hydrophilicity and suitable mechanical properties is subsequently utilized for preparation of electrospun tubular scaffolds. In vitro assays demonstrate that the zSePEUU electrospun membranes can inhibit protein adsorption and facilitate cell proliferation. Due to the in situ catalysis of diselenide, it is supposed that vasoregulatory nitric oxide (NO) can be generated to promote endothelialization. Then, the zSePEUU electrospun tubular scaffold remains vascular patency with formation of endothelial coverage and collagen deposition during in vivo implantation in a rat abdominal aorta interposition model for 4 weeks in comparison with the PCL control. Therefore, zwitterionic diselenide-containing zSePEUU with controllable NO generation provides a synergistic strategy for vascular regeneration. STATEMENT OF SIGNIFICANCE: Transplantation of vascular grafts is one of the effective approaches for treating cardiovascular diseases, however, this remains a challenge with the small-diameter vascular grafts. Herein, electrospun fibrous scaffolds made from elastic zwitterionic diselenide-containing poly(ester urethane)urea (zSePEUU) are reported, displaying increased hydrophilicity and compliance. By using equal amounts of sulfobetaine-diol and poly(ε-caprolactone)-diol, the zSePEUU electrospun scaffold exhibits optimal mechanical properties and nitric oxide-generating ability. Evaluation in a rat abdominal aorta interposition model suggests that the zSePEUU electrospun scaffold can achieve a high level of endothelial coverage and vascular regeneration. This finding provides a feasible method to address the issue of rapid endothelialization for long-term patency in vascular regeneration.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426786","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":"Emerging near-infrared targeting diagnostic and therapeutic strategies for ischemic cardiovascular and cerebrovascular diseases.","authors":"Mengran Yu, Huijun Wu, Haoyuan Hu, Ye Cheng, Youran Qin, Kaiqing Yang, ChangHao Hu, Wei Guo, Yuxuan Kong, Weiwen Zhao, Xueqin Cheng, Hong Jiang, Songyun Wang","doi":"10.1016/j.actbio.2024.11.027","DOIUrl":"10.1016/j.actbio.2024.11.027","url":null,"abstract":"<p><p>Ischemic cardiovascular and cerebrovascular diseases (ICCDs), including thrombosis, ischemic stroke and atherosclerosis, represent a significant threat to human health, and there is an urgent requirement for the implementation of emerging diagnostic and therapeutic approaches to improve symptoms and prognosis. As a promising noninvasive modality offering high spatial and temporal resolution with favorable biocompatible properties, near-infrared (NIR) light has demonstrated a vast and profound potential in the biomedical field in recent years. Meanwhile, nanomedicine carriers are undergoing rapid development due to their high specific surface area, elevated drug loading capacity, and unique physicochemical properties. The combination of NIR light with targeted nanoprobes modified with different functional components not only maintains the high penetration depth of NIR irradiation in biological tissues but also significantly enhances the targeting specificity at the lesion site. This strategy allows for the realization of on-demand drug release and photothermal effects, thus inspiring promising avenues for the diagnosis and treatment of ICCDs. However, the clinical translation of NIR imaging and therapy is still hindered by significant obstacles. The existing literature has provided a comprehensive overview of the advancements in NIR-based nanomedicine research. However, there is a notable absence of reviews that summarize the NIR-mediated targeting strategies against ICCDs in imaging and therapy. Therefore, this review concludes the application of the emerging targeting probes combined with NIR radiation for ICCDs classified by molecular targets, analyzes the current challenges, and provides improvement strategies and prospects for further clinical translation. STATEMENT OF SIGNIFICANCE: Ischemic cardiovascular and cerebrovascular diseases (ICCDs) represent a significant threat to human health. Recently, near-infrared (NIR) light combined with targeting probes have been employed for the diagnosis and treatment of ICCDs, offering exceptional advantages including rapid feedback, high penetration depth, on-demand drug release, and favorable biocompatibility. However, there is a notable absence of reviews that summarize the NIR light-mediated targeting strategies for the imaging and therapy of ICCDs. Therefore, this review summarizes the emerging targeting probes combined with NIR light classified by molecular targets, and the proposes potential improvement strategies for clinical translation. This review elucidates the potential and current status of NIR-based techniques in ICCDs, while also serving as a reference point for additional targeted therapeutic strategies for ICCDs.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693999","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":"In vitro vascularization improves in vivo functionality of human engineered cardiac tissues.","authors":"Hanjun Li, Ilya Shadrin, Abbigail Helfer, Karen Heman, Lingjun Rao, Caroline Curtis, Gregory M Palmer, Nenad Bursac","doi":"10.1016/j.actbio.2024.11.014","DOIUrl":"10.1016/j.actbio.2024.11.014","url":null,"abstract":"<p><p>Engineered human cardiac tissues hold great promise for disease modeling, drug development, and regenerative therapy. For regenerative applications, successful engineered tissue engraftment in vivo requires rapid vascularization and blood perfusion post-implantation. In the present study, we engineered highly functional, vascularized cardiac tissues (\"cardiopatches\") by co-culturing human induced pluripotent stem cell-derived cardiomyocytes (hiPSCCMs) and endothelial cells (hiPSC-ECs) in optimized serum-free media. The vascularized cardiopatches displayed stable capillary networks over 4 weeks of culture, the longest reported in the field, while maintaining high contractile stress (>15 mN/mm²) and fast conduction velocity (>20 cm/s). Robustness of the method was confirmed using two distinct hiPSC-EC sources. Upon implantation into dorsal-skinfold chambers in immunocompromised mice, in vitro vascularized cardiopatches exhibited improved angiogenesis compared to avascular implants. Significant lumenization of the engineered human vasculature and anastomosis with host mouse vessels yielded the formation of hybrid human-mouse capillaries and robust cardiopatch perfusion by blood. Moreover, compared to avascular tissues, the implanted vascularized cardiopatches exhibited significantly higher conduction velocity and Ca²⁺ transient amplitude, longitudinally monitored in live mice for the first time. Overall, we demonstrate successful 4-week vascularization of engineered human cardiac tissues without loss of function in vitro, which promotes tissue functionality upon implantation in vivo. STATEMENT OF SIGNIFICANCE: Complex interactions between cardiac muscle fibers and surrounding capillaries are critical for everyday function of the heart. Tissue engineering is a powerful method to recreate functional cardiac muscle and its vascular network, which are both lost during a heart attack. Our study demonstrates in vitro engineering of dense capillary networks within highly functional engineered heart tissues that successfully maintain the structure, electrical, and mechanical function long-term. In mice, human capillaries from these engineered tissues integrate with host mouse capillaries to allow blood perfusion and support improved implant function. In the future, the developed vascularized engineered heart tissues will be used for in vitro studies of cardiac development and disease and as a potential regenerative therapy for heart attack.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634212","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}

{"title":"Targeting cardiac resident CCR2+ macrophage-secreted MCP-1 to attenuate inflammation after myocardial infarction.","authors":"Jiaxing Wen, Ya Guan, Hong Niu, Yu Dang, Jianjun Guan","doi":"10.1016/j.actbio.2024.08.025","DOIUrl":"10.1016/j.actbio.2024.08.025","url":null,"abstract":"<p><p>After myocardial infarction (MI), cardiac resident CCR2+ macrophages release various cytokines and chemokines, notably monocyte chemoattractant protein-1 (MCP-1). MCP-1 is instrumental in recruiting CCR2+ monocytes to the damaged region. The excessive arrival of these monocytes, which then become macrophages, perpetuates inflammation at the site of injury. This continuous inflammation leads to adverse tissue remodeling and compromises cardiac function over time. We hypothesized that neutralizing the MCP-1 secreted by cardiac resident CCR2+ macrophages can mitigate post-MI inflammation by curtailing the recruitment of monocytes and their differentiation into macrophages. In this work, we developed nanoparticles that target the infarcted heart, specifically accumulating in the damaged area after intravenous (IV) administration, and docking onto CCR2+ macrophages. These nanoparticles were designed to slowly release an MCP-1 binding peptide, HSWRHFHTLGGG (HSW), which neutralizes the upregulated MCP-1. We showed that the HSW reduced monocyte migration, inhibited pro-inflammatory cytokine upregulation, and suppressed myofibroblast differentiation in vitro. After IV delivery, the released HSW significantly decreased monocyte recruitment and pro-inflammatory macrophage density, increased cardiac cell survival, attenuated cardiac fibrosis, and improved cardiac function. Taken together, our findings support the strategy of MCP-1 neutralization at the acute phase of MI as a promising way to alleviate post-MI inflammation. STATEMENT OF SIGNIFICANCE: After a myocardial infarction (MI), CCR2+ macrophages resident in the heart release various cytokines and chemokines, notably monocyte chemoattractant protein-1 (MCP-1). MCP-1 is instrumental in attracting CCR2+ monocytes to the damaged region. The excessive arrival of these monocytes, which then become macrophages, perpetuates inflammation at the site of injury. This continuous inflammation leads to adverse tissue remodeling and compromises cardiac function over time. In this work, we tested the hypothesis that neutralizing the MCP-1 secreted by cardiac CCR2+ macrophages can mitigate post-MI inflammation by curtailing the recruitment of monocytes.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057491","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}

{"title":"Mitochondria-targeted sonodynamic modulation of neuroinflammation to protect against myocardial ischemia‒reperfusion injury.","authors":"Haoyuan Hu, Qian Li, Jiale Wang, Ye Cheng, Jiahui Zhao, Changhao Hu, Xinyue Yin, Yuzhe Wu, Ruiqi Sang, Hong Jiang, Yao Sun, Songyun Wang","doi":"10.1016/j.actbio.2024.08.003","DOIUrl":"10.1016/j.actbio.2024.08.003","url":null,"abstract":"<p><p>Sympathetic hyperactivation and inflammatory responses are the main causes of myocardial ischemia‒reperfusion (I/R) injury and myocardial I/R-related ventricular arrhythmias (VAs). Previous studies have demonstrated that light-emitting diodes (LEDs) could modulate post-I/R neuroinflammation, thus providing protection against myocardial I/R injury. Nevertheless, further applications of LEDs are constrained due to the low penetration depth (<1 cm) and potential phototoxicity. Low-intensity focused ultrasound (LIFU), an emerging noninvasive neuromodulation strategy with deeper penetration depth (∼10 cm), has been confirmed to modulate sympathetic nerve activity and inflammatory responses. Sonodynamic therapy (SDT), which combines LIFU with sonosensitizers, confers additional advantages, including superior therapeutic efficacy, precise localization of neuronal modulation and negligible side effects. Herein, LIFU and SDT were introduced to modulate post-myocardial I/R neuroinflammation to protect against myocardial I/R injury. The results indicated that LIFU and SDT inhibited sympathetic neural activity, suppressed the activation of astrocytes and microglia, and promoted microglial polarization towards the M2 phenotype, thereby attenuating myocardial I/R injury and preventing I/R-related malignant VAs. These insights suggest that LIFU and SDT inspire a noninvasive and efficient neuroinflammatory modulation strategy with great clinical translation potential thus benefiting more patients with myocardial I/R in the future. STATEMENT OF SIGNIFICANCE: Myocardial ischemia-reperfusion (I/R) may cause I/R injury and I/R-induced ventricular arrhythmias. Sympathetic hyperactivation and inflammatory response play an adverse effect in myocardial I/R injury. Previous studies have shown that light emitting diode (LED) can regulate I/R-induced neuroinflammation, thus playing a myocardial protective role. However, due to the low penetration depth and potential phototoxicity of LED, it is difficult to achieve clinical translation. Herein, we introduced sonodynamic modulation of neuroinflammation to protect against myocardial I/R injury, based on mitochondria-targeted nanosonosensitizers (CCNU980 NPs). We demonstrated that sonodynamic modulation could promote microglial autophagy, thereby preventing myocardial I/R injury and I/R-induced ventricular arrhythmias. This is the first example of sonodynamic modulation of myocardial I/R-induced neuroinflammation, providing a novel strategy for clinical translation.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914782","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":"High molecular weight hyaluronic acid-liposome delivery system for efficient transdermal treatment of acute and chronic skin photodamage.","authors":"Hui Xing, Xiangjun Pan, Yihan Hu, Yuhui Yang, Ziyi Zhao, Huanqi Peng, Jianjin Wang, Shanying Li, Yunfeng Hu, Guowei Li, Dong Ma","doi":"10.1016/j.actbio.2024.05.026","DOIUrl":"10.1016/j.actbio.2024.05.026","url":null,"abstract":"<p><p>Photodamage is one of the most common causes of skin injury. High molecular weight hyaluronic acid (HHA) has shown immense potential in the treatment of skin photodamage by virtue of its anti-inflammatory, reparative, and antioxidative properties. However, due to its large molecular structure of HHA, HHA solution could only form a protective film on the skin surface in conventional application, failing to effectively penetrate the skin, which necessitates the development of new delivery strategies. Liposomes, with a structure similar to biological membranes, have garnered extensive attention as transdermal drug delivery carriers because of their advantages in permeability, dermal compatibility, and biosafety. Herein, we have developed a HHA-liposome transdermal system (HHL) by embedding HHA into the liposome structure using reverse evaporation, high-speed homogenization, and micro-jet techniques. The effective penetration and long-term residence of HHA in skin tissue were multidimensionally verified, and the kinetics of HHA in the skin were extensively studied. Moreover, it was demonstrated that HHL significantly strengthened the activity of human keratinocytes and effectively inhibits photo-induced cellular aging in vitro. Furthermore, a murine model of acute skin injury induced by laser ablation was established, where the transdermal system showed significant anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair, thereby demonstrating immense potential in accelerating skin wound healing. Meanwhile, HHL significantly ameliorated skin barrier dysfunction caused by simulated sunlight exposure, inhibited skin erythema, inflammatory responses, and oxidative stress, and promoted collagen expression in a chronic photodamage skin model. Therefore, this transdermal delivery system with biocompatibility represents a promising new strategy for the non-invasive application of HHA in skin photodamage, revealing the significant potential for clinical translation and broad application prospects. STATEMENT OF SIGNIFICANCE: The transdermal system utilizing hyaluronic acid-based liposomes enhances skin permeability and retains high molecular weight hyaluronic acid (HHL). In vitro experiments with human keratinocytes demonstrate significant skin repair effects of HHL and its effective inhibition of cellular aging. In an acute photodamage model, HHL exhibits stronger anti-inflammatory and immunosuppressive properties, promoting skin proliferation and scar repair. In a chronic photodamage model, HHL significantly improves skin barrier dysfunction, reduces oxidative stress induced by simulated sunlight, and enhances collagen expression.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":"171-187"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961239","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}