Acta biomaterialia最新文献

{"title":"Beyond Gadolinium: The Potential of Manganese Nanosystems in MRI and Multimodal Imaging Agents.","authors":"Lorenzo Tei, Mauro Botta, Carlos F G C Geraldes","doi":"10.1016/j.actbio.2025.05.058","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.05.058","url":null,"abstract":"<p><p>Manganese-based nanoparticles (Mn-NPs) hold great promise as MRI contrast agents and components of theranostic nanoplatforms, serving as a promising alternative to the more established gadolinium(III)-based nanosystems. This potential stems from their unique physicochemical properties and improved safety profile. This review introduces the fundamental principles of relaxation to highlight the key physicochemical characteristics of Mn-based nanosystems that influence their effectiveness. We primarily examine two oxidation states of manganese, Mn(II) and Mn(III), to demonstrate the efficacy of Mn-NPs as relaxation probes, with a brief discussion of one Mn(IV) system. Subsequently, we review recent studies on Mn-NP-based MRI contrast agents, focusing on the correlation between nanoparticle structure and the oxidation state of the paramagnetic centre. For Mn(II), the most common strategy involves utilizing stable Mn-chelates anchored to or encapsulated within the nanoparticles. In contrast, for the higher oxidation state, Mn(III), Mn(III)-porphyrin and phthalocyanine NPs are the primary non-Mn oxide nanosystems of choice. Regarding nanoplatform composition, Mn(II)-based platforms utilizing lipids (micelles or liposomes), polysaccharides (nanogels), dendrimers, metal-organic frameworks, inorganic NPs, and silicas are among the most frequently investigated. While numerous in vitro and in vivo animal MRI studies of Mn nanoplatforms have been reported, none have yet received clinical approval. We describe innovative surface modification and functionalization procedures designed to improve NP characteristics (e.g., size, stability, dispersibility, relaxivity, targeting, and toxicity) and impart multifunctionality for multimodal imaging. These strategies may provide valuable guidance for the development of Mn-NPs toward future clinical applications, particularly in cancer theranostics. STATEMENT OF SIGNIFICANCE: This review provides a critical analysis of the current landscape of Mn-based nanoparticles, which are increasingly being explored as MRI contrast agents and for multimodal imaging. This growing interest is largely driven by concerns over the potential toxicity and environmental impact of traditional Gd-based systems. The review introduces the key structural and dynamic parameters that determine the effectiveness of these nanosystems, highlighting their direct relationship with molecular design. It also examines the crucial stability and kinetic inertness requirements that influence their development. By critically discussing selected recent examples across a diverse range of nanosystems, including micelles, liposomes, silica-based platforms, and MOFs, this review identifies existing challenges and provides key insights to guide their future clinical translation.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144164286","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":"Poly(vinyl alcohol) reduced and capped gold nanoparticles as contrast enhancers to target and improve detection of medial calcification.","authors":"Tao Song, Kyoungmi Bak, Dahyun Kyung, Monzur Murshed, Marta Cerruti","doi":"10.1016/j.actbio.2025.05.059","DOIUrl":"10.1016/j.actbio.2025.05.059","url":null,"abstract":"<p><p>Medial calcification is the pathological deposition of calcium phosphate (CaP) minerals in the elastin-rich medial layers of arteries, leading to vessel stiffening and increased risk of heart failure. There are no drugs to treat medial calcification, and thus it would be important to detect the disease as early as possible to enable adequate prevention. In the clinic, X-ray based computed tomography (CT) is used to diagnose medial calcification, but the few and small CaP minerals present in early stages of medial calcification do not provide enough X-ray contrast to be detectable by CT. Herein, we propose poly(vinyl alcohol) (PVA) reduced and capped gold nanoparticles (PVA@AuNPs) to target medial calcification and improve its detection in early stages. AuNPs can greatly absorb X-rays and thus work as contrast enhancers for CT. Results show that PVA@AuNPs can bind to CaP minerals containing hydroxyl ions on their surface, most likely via hydrogen-bond interactions with PVA capping polymers; indeed, mineral binding efficiency depends on the hydrolysis degree of PVA. AuNPs prepared from 99 %+ hydrolyzed PVA (PVA99@AuNPs) bind selectively to calcified vs. non-calcified elastin in vitro, and in vivo they improve the contrast of medial calcification in 4-week-old matrix Gla-protein deficient mice imaged through micro-CT. STATEMENT OF SIGNIFICANCE: The few and small calcium phosphate (CaP) minerals present in early stages of medial calcification do not provide enough contrast for clinical detection via computed tomography (CT). Herein, we show that 99 %+ hydrolyzed poly(vinyl alcohol) reduced and capped gold nanoparticles (PVA99@AuNPs) selectively bind CaP minerals in medial calcification, thus improving their contrast and (micro)CT detection. Unlike previously proposed targeting agents, PVA99@AuNPs bind to CaP mineral phases present in early-stage medial calcification but not to the extracellular matrix onto which minerals are deposited, thus enabling accurate and specific targeting. Their straightforward synthesis and biocompatibility significantly enhance their potential for clinical translation. Earlier detection of medial calcification would greatly improve disease management, particularly important since no treatments are available for the disease.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153022","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}

{"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}