Acta biomaterialia最新文献

{"title":"Distinguishing shear and tensile myocardial wall stiffness using ex vivo anisotropic Magnetic Resonance Elastography.","authors":"Cyril Tous, Guillaume Flé, Stanislas Rapacchi, Matthew McGarry, Philip Bayly, Keith Paulsen, Curtis L Johnson, Elijah Van Houten","doi":"10.1016/j.actbio.2025.06.031","DOIUrl":"10.1016/j.actbio.2025.06.031","url":null,"abstract":"<p><p>The organized myofiber structure within the myocardium indicates its mechanical anisotropy. By projecting the MR Elastography (MRE) stiffness matrix along either the myocardial fiber or sheet orientations determined by Diffusion Tensor Imaging (DTI), anisotropic MRE (aMRE) maps axial and transverse shear and Young's moduli into three tensile and six shear deformation modes. Ten healthy ex vivo swine hearts were imaged three times at 3T using MRE and DTI sequences. aMRE results showed a within-subject coefficient of variation at 19% for the fiber model and 28% for the sheet model across specimens and metrics, with coefficients lower than 15% for seven of the ten specimens across models. Repeatability coefficient of ±0.5 kPa for Young's moduli and ±0.17 kPa for shear's moduli, demonstrating repeatability within the 95% agreement limit. Isotropic MRE underestimated stiffnesses by 31% compared to aMRE, where anisotropic moduli aligned more closely with prior finite element studies and some mechanical loading tests. The myocardium's anisotropic elasticity reflects with its helicoidal myofiber microstructure, with mid-wall circumferential fibers requiring twice the force to deform as longitudinal fibers at the epicardium or endocardium. At the mid-wall, fiber model values were μ<sub>ax</sub> = 1.9 ± 0.1 kPa, μ<sub>tra</sub> = 1.3 ± 0.1 kPa, E<sub>ax</sub> = 5.6 ± 0.4 kPa, and E<sub>tra</sub> = 3.8 ± 0.3 kPa. Identified deformation modes included: (FF), (NN), (FF or SS), (NN or SS), (SN or NS), (FN or FS), (SF or FS), and (SN or NF), where N is normal to both fiber (F) and sheet (S) orientations. By aligning elasticity matrices more accurately with myocardial architecture than isotropic MRE, aMRE was able to reliably measure shear and Young's moduli in ex vivo swine hearts. These mappings of deformation modes may bring myocardial stiffness assessment closer to clinical application, providing a foundation for a non-invasive methodology capable of true mechanical characterization of the cardiac wall using MR imaging. STATEMENT OF SIGNIFICANCE: The myocardium's anisotropic elasticity, due to its helicoidal myofiber structure, is revealed through anisotropic MR elastography, using fiber and sheet elastic models. Mid-wall circumferential fibers require twice the force to deform equally compared to epicardial or endocardial fibers. Characterizing shear and Young's moduli across cardiac modes offers noninvasive measures of ventricular compliance, comparable to pressure-volume relationships. This could enhance early diagnosis of \"stiff heart syndrome\" and clarify its underlying mechanisms. Additionally, it aids understanding of myocardial pathologies, including amyloidosis, hypertrophic and dilated cardiomyopathies, and ischemic damage. By characterizing tensile and shear interactions, it may inform diagnosis and treatment of conduction issues and arrhythmia, where tissue has lost its normal mechanical behavior, while patient-specific models could optimiz","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337249","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":"Mechanically-adaptive Janus hydrogel enhances scarless tendon healing with tissue-adhesion prevention.","authors":"Lu Tan, Yanqiu Wang, Chenxi Huyan, Menghuan Li, Dong Liu, Minghan Liu, Zhong Luo, Kaiyong Cai, Yan Hu","doi":"10.1016/j.actbio.2025.06.032","DOIUrl":"10.1016/j.actbio.2025.06.032","url":null,"abstract":"<p><p>Tendon injuries are common orthopedic traumas but often respond poorly to existing surgical treatments, which is largely attributed to the misrouted extracellular matrix (ECM) generation and tendon adhesion formation. Herein, we report a Janus dynamic hydrogel-based patch with asymmetric tissue adhesive property for dressing damaged tendons, leading to scarless restoration of their structural and functional properties. The Janus hydrogel patch (PCP) is prepared by growing a tendon-adhesive layer (CP layer) constituted by dihydrocaffeic acid-containing chitosan (CS-HCA), ureido-pyrimidinone (UPy)-grafted gelatin and catechol-modified waterborne polyurethane atop a pre-semicured anti-adhesive polyurethane layer (PU layer) through in-situ gelatinization, which potentiates firm adhesion to the damaged tendon while avoiding post-surgical adhesion between tendon and surrounding tissues. The heavy mechanical load of tendon would trigger the formation of abundant orderly aligned crystalline domains through stress-induced crystallization that substantially enhances the mechanical strength of PCP, which not only improve its mechanical resilience in the complex biomechanical environment of tendons but also provides optimal biomechanical stimulation to enhance the robustness of the healing tendon through ECM remodeling. Furthermore, the implanted PCP could effectively suppress inflammation-relevant signaling pathways to avoid synechia and further accelerate tendon healing while preventing scar formation. The PCP offers a promising approach for tendon injury treatment in the clinics. STATEMENT OF SIGNIFICANCE: This asymmetric tissue-adhesive double-layer Janus hydrogel patch (PCP) can effectively stabilize dynamic tissue wounds and adequately withstands the mechanical stresses via a strain-induced crystallization (SIC) strategy, thereby preventing its deterioration and rupture in the context of frequent movements and large-amplitude motions. When implanted on damaged tendons, the bio-repelling nature and smooth surface of the anti-adhesive polyurethane (PU) layer effectively prevent postsurgical adhesion and reduce secondary surgery risks. Furthermore, the hydroxycinnamic acid (HCA) component within the CP layer alleviates local inflammation by suppressing inflammation-associated signaling pathways, concurrently inhibiting synechia formation and accelerating tendon regeneration. This integrated system establishes a comprehensive clinical approach for achieving scarless tendon repair while maintaining effective tissue-adhesion prevention.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337250","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":"Black Phosphorus Nanosheets Promote Neuronal Differentiation of Neural Stem Cells through Adhesion and Pinocytosis for Spinal Cord Injury Repair.","authors":"Lu Chen, Lusen Shi, Tianhui Wei, Haoran Liu, Zihang Wang, Hongliang Wang, Na Li, Shiqing Feng","doi":"10.1016/j.actbio.2025.06.030","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.06.030","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a severe neurological and pathological disorder, but there are few effective treatments that can significantly promote functional recovery after SCI. Neural stem cell (NSC) transplantation therapy is considered a promising approach to repair neural connection and enhance functional recovery. However, a series of pathological changes at the injury site make the microenvironment unfavorable for NSC neuronal differentiation. In this study, black phosphorus nanosheets (BPNSs), a kind of nanomaterial which degraded into phosphate anions, exhibited good biocompatibility and effective function on regulating NSC differentiation. In vitro, BPNSs can promote neuronal differentiation of NSC by upregulating the p53 signaling pathway via activating membrane receptors and intracellular receptors mediated by its adhesin and cell pinocytosis. In vivo, BPNSs-treated NSCs transplantation could promote neural regeneration and functional recovery effectively. In conclusion, our results suggest that BPNSs have the potential to be a nanomedical strategy for the repair of SCI. STATEMENT OF SIGNIFICANCE: Black phosphorus nanosheets (BPNSs), which are composed of the single chemical element phosphorus that is a fundamental component of biological systems, exhibit good biocompatibility, as they predominantly degrade into phosphate anions. BPNSs are quickly internalized by neural stem cells (NSCs) within 6 hours and can promote NSC neuronal differentiation by upregulating the p53 signaling pathway. Transplantation of NSCs pre-treated with BPNSs effectively promotes nerve regeneration and facilitates significant functional recovery following spinal cord injury.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The foreign body response to biomaterial implants is reduced by co-inhibition of TLR2 and TLR4.","authors":"Brittany J Thompson, Emma L Carillion, Scott Alper, Stephanie J Bryant","doi":"10.1016/j.actbio.2025.06.020","DOIUrl":"10.1016/j.actbio.2025.06.020","url":null,"abstract":"<p><p>The foreign body response (FBR) is a formidable reaction that occurs to any non-biological implantable biomaterial and results in fibrous encapsulation. Non-specific protein adsorption is the first stage of the FBR and is thought to initiate the response by activation of innate immune cells. Here we show that Toll-like receptors (TLRs) 2 and 4 are the primary receptors responsible for recognizing surface adsorbed proteins as damage associated molecular patterns (DAMPs) and they determine the material dependent FBR. An in vitro model using multiple biomaterials identified that macrophages, not neutrophils, respond to surface-adsorbed plasma via TLR2 and/or TLR4 and that deletion of both was required to inhibit activation across all materials. In the more complex in vivo environment, simultaneous deletion of TLR2 and TLR4 nearly abrogated the FBR to multiple biomaterials and eliminated the material dependencies in a subcutaneous implant mouse model. Deletion of either TLR2 or TLR4 showed either no effect or a partial reduction, depending on the material, demonstrating that TLRs determine the material-dependent FBR in vivo. Collectively, we identified TLR2 and TLR4 as necessary receptors for the FBR and implicate macrophage recognition of DAMPs of surface-adsorbed proteins, which vary depending on the material, as the main driver initiating the FBR. Our findings establish TLR2 and TLR4 as therapeutic targets to evade the FBR across a range of implantable materials. STATEMENT OF SIGNIFICANCE: Synthetic biomaterials when implanted elicit a foreign body response (FBR) leading to fibrous encapsulation. The mechanisms however are not fully understood. When a biomaterial is implanted, proteins non-specifically adsorb to the material. These proteins may act as damaged associated molecular patterns (DAMPs) to induce inflammation. Toll like receptor (TLR) 2 and 4 are known receptors that recognize DAMPs. This work investigated several different biomaterials and found that TLR2 and TLR4 mediate the FBR in a material-dependent manner. Deleting both TLR2 and TLR4 was necessary to inhibit significantly fibrous capsule formation across all materials tested. Our findings provide direct evidence that DAMPs are the main driver of the FBR and establish TLR2/4 as potential therapeutic targets to evade the FBR.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295482","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":"NIR-II Responsive Copper-Nitrogen Doped Photocatalysts for Pyroptosis and Cuproptosis.","authors":"Qinglin Wei, Xuejiao Song, Xiaorui Wang, Yawen Chen, Wenjun Wang, Ping Sun, Xiaochen Dong","doi":"10.1016/j.actbio.2025.06.029","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.06.029","url":null,"abstract":"<p><p>Based on their distinctive manners of driving cell death, cuproptosis and pyroptosis exhibit significant potential in overcoming the apoptosis resistance of cancer cells. Nevertheless, limited copper concentrations and complex tumor microenvironment (TME) severely constrain the therapeutic efficacy. Herein, DSPE-PEG₂₀₀₀ modified copper-nitrogen-doped carbon-based photocatalysts (Cu-NC@PEG) are developed as photo-activated reactive oxygen species (ROS) amplification systems to trigger pyroptosis and cuproptosis in a synergistic manner. Cu-NC@PEG enriches in tumor cells and generates a large amount of superoxide anions under the second near-infrared region (NIR-II) laser irradiation, followed by further induction of cell pyroptosis through caspase-mediated cleavage of Gasdermin D (GSDMD). The copper ions released from Cu-NC@PEG in the acidic TME can not only generate ·OH and consume the antioxidants to enhance ROS-induced pyroptosis, but also effectively activate cuproptosis through Cu⁺-mediated dihydrolipoamide S-acetyltransferase aggregation and Fe-S cluster protein loss. Simultaneously, the mitochondrial damage induced by pyroptosis leads to a considerable efflux of ATP and the restricted ATP availability could enhance the disruption of copper metabolic homeostasis, thereby potentiating cuproptosis. The increased tumor-inhibiting effects of the combined induction of cuproptosis and pyroptosis could be achieved. STATEMENT OF SIGNIFICANCE: 1. NIR-II photo-activated copper-nitrogen-doped carbon-based photocatalysts (Cu-NC@PEG) were developed. 2. ROS amplification was achieved based on the photo catalytic properties and Fenton-like reaction of Cu-NC@PEG. 3. Therapeutic efficacy was enhanced via ROS-induced pyroptosis and Cu⁺-mediated cuproptosis.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487417","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":"Nano-carriers mediate reciprocally chained promotion between ROS and mitochondrial calcium overload for enhanced antitumor therapy.","authors":"Zhihao Zhao, Ke Ling, Jun Yan, Zhexiang Wang, Chuntao Chen, Dongping Sun, Jian Liu","doi":"10.1016/j.actbio.2025.06.009","DOIUrl":"10.1016/j.actbio.2025.06.009","url":null,"abstract":"<p><p>Calcium ions (Ca²⁺) and reactive oxygen species (ROS) play pivotal roles in cellular signaling and the regulation of diverse biological processes. Complex and dynamic interactions between Ca²⁺ and ROS signaling pathways are often exploited by tumor cells to resist therapeutic interventions. In this study, we present a strategy of cancer treatment based on the reciprocally reinforcing interplay between ROS burst and mitochondrial calcium overload. The major components of our nano carriers integrate CaCO₃ nanoparticles loaded with glucose oxidase (GOx), and copper peroxide nanodots (CPDs) in a DSPE-S-S-PEG-modified liposomal format (abbr. GCCL,). This hybrid nanosystem is designed to facilitate controlled and accelerated release of Ca²⁺ and ROS, thereby establishing dual positive feedback loops that amplify both mitochondrial calcium accumulation and oxidative stress. By harnessing this synergistic cycle, our platform enhances the efficacy of chemodynamic therapy and calcium-induced mitochondrial damage, offering a promising strategy for translational cancer treatment. STATEMENT OF SIGNIFICANCE: Here we report a strategy of antitumor therapeutic by designing a dual positive feedback loop of pH-driven self-accelerated Ca²⁺ and H₂O₂ release, thus reciprocally promoting ROS production and mitochondrial calcium overload for tumor eradication. After cellular uptake of GCCL, releasing of the cargos inside the liposomes can introduce a cascade of chemical reactions and biochemical cues, leading to calcium overload and ROS burst. These two major effects are mutually linked with each other, which is utilized by our GCCL design to fuel the positive feedback loops for tumor cell apoptosis in vitro and effective cancer ablation in vivo. Our nano therapy stands out with improved tumor suppression, with a lower dosage of copper element in the treatments of 4T1 xenograft tumor-bearing BALB/c mice model.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295481","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":"Decellularized amnion membrane-based thermosensitive vaginal hydrogel enhances ritodrine efficacy and reduces systemic side effects in preterm birth treatment.","authors":"Yu Xin, Yue Chen, Xiaojun Zhu, Ying Zhang, Maiqi Kong, Huidi Jiang, Xiao Li, Weidong Fei, Caihong Zheng","doi":"10.1016/j.actbio.2025.06.024","DOIUrl":"10.1016/j.actbio.2025.06.024","url":null,"abstract":"<p><p>Preterm birth remains a major cause of maternal and neonatal mortality, primarily due to the lack of effective clinical interventions. Ritodrine, a typical β₂-adrenoceptor agonist with low cost and proven clinical efficacy, faces restrictions in many developed countries because of its systemic side effects. To overcome the clinical limitations of ritodrine, this study developed a decellularized amnion membrane (dAM)-derived thermosensitive hydrogel for vaginal delivery of ritodrine (dAM@Rit). The resulting dAM@Rit exhibited favorable temperature sensitivity, optimal rheological properties, sustained drug release, low cytotoxicity, and high biocompatibility. In vivo fluorescence analyses confirmed the uterine-specific distribution of the drugs through the vaginal delivery of dAM@Rit, facilitated by the uterine first-pass effect. Pharmacodynamic evaluation revealed that dAM@Rit maintenance therapy reduced the preterm birth rate due to the anti-inflammatory properties of dAM and the β₂-adrenoceptor antagonizing effect of ritodrine. Notably, the dAM@Rit formulation also substantially mitigated ritodrine-induced adverse reactions, such as pulmonary edema and rhabdomyolysis. In conclusion, our findings offered a promising strategy to optimize the clinical application of ritodrine for managing preterm birth while minimizing its systemic side effects. STATEMENT OF SIGNIFICANCE: 1. This study designed a thermosensitive hydrogel for the vaginal delivery of ritodrine, achieving targeted uterine drug delivery through the uterine first-pass effect. 2. The hydrogel utilizes decellularized amnion membrane (dAM) as its matrix, which not only exhibits high biocompatibility but also enhances the therapeutic efficacy of ritodrine through its anti-inflammatory properties, synergistically treating premature labor. 3. Compared with intravenous or oral administration, the dAM-based vaginal hydrogel significantly reduces the adverse effects of ritodrine on both mothers and fetuses, offering a safer alternative for the management of preterm birth. 4. This work demonstrates the application of human amniotic membrane-derived biomaterial for pregnancy-related diseases, highlighting the importance of balancing efficacy and safety in clinical applications.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295478","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 nanoplatform mediates hypoxia-adenosine axis disruption and PD-L1 knockout for enhanced MRI-guided chemodynamic-immunotherapy.","authors":"Mengyu Sun, Cheng Ni, Aiyu Li, Junjie Liu, Honghua Guo, Fanyong Xu, Kangan Li, Xueyan Cao, Xiangyang Shi, Rui Guo","doi":"10.1016/j.actbio.2025.06.021","DOIUrl":"10.1016/j.actbio.2025.06.021","url":null,"abstract":"<p><p>Malignant melanoma is an extremely aggressive and fatal form of skin cancer due to the limited efficacy of conventional therapies. While immune checkpoint blockade therapy and chemodynamic therapy (CDT) have emerged as promising strategies for melanoma treatment, their effectiveness is compromised by the immunosuppressive and complex tumor microenvironment (TME). Here, cancer cell membrane-camouflaged nanoplatforms (PPMC@CM) were developed to co-deliver the CRISPR/Cas9-PD-L1 system and manganese dioxide nanoparticles (MnO₂ NPs) for magnetic resonance imaging (MRI)-guided CDT and enhanced immunotherapy. The formed PPMC@CM could efficiently accumulate at tumor sites by homologous targeting, generate O₂ to relieve hypoxia, and deplete glutathione (GSH) to enhance Mn²⁺-mediated Fenton-like reactions for enhanced CDT. Meanwhile, CRISPR/Cas9-mediated PD-L1 knockout effectively suppressed the PD-L1 expression, while hypoxia relief attenuated the immunosuppressive hypoxia-CD39/CD73-adenosine (ADO) pathway, thereby boosting the PD-L1-mediated immunotherapy. In vivo experimental results demonstrated that PPMC@CM nanoplatform could efficiently inhibit the growth and metastasis of melanoma by enhanced CDT and amplified immunotherapy, and provide targeted MRI of tumors. This work presents a novelty strategy to design biomimetic theranostic nanoplatform for melanoma by the combination of CDT and improved immunotherapy with CRISPR/Cas9-PD-L1 system and hypoxia-ADO axis inhibition. STATEMENT OF SIGNIFICANCE: Malignant melanoma is a highly aggressive and treatment-refractory skin cancer, where conventional therapies exhibit limited efficacy and immune checkpoint blockade (ICB) is often compromised by the immunosuppressive tumor microenvironment (TME). To address these challenges, we developed a biomimetic nanoplatform (PPMC@CM) to codeliver MnO₂ nanoparticles and the CRISPR/Cas9-PD-L1 gene-editing system for MRI-guided chemodynamic therapy and enhanced immunotherapy. The PPMC@CM nanoplatform could efficiently accumulate at tumor sites by homologous targeting and relieve hypoxia to suppress the hypoxia-CD39/CD73-adenosine immunosuppressive axis. Additionally, the CRISPR/Cas9-mediated PD-L1 knockout significantly suppresses PD-L1 expression, thereby boosting ICB efficacy. Moreover, PPMC@CM could deplete glutathione in the TME to amplify Mn²⁺-mediated Fenton-like reactions for enhanced chemodynamic therapy. This research represents a promising theranostic nanoplatform for melanoma by combining chemodynamic therapy and immunotherapy.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295475","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":"Homocysteine leads to aortic stiffening in a rabbit model of atherosclerosis.","authors":"Francesca Bogoni, Markus S Brunner, Gunter Almer, Gerd Hörl, Yuriy G Tehlivets, Gerhard Sommer, Oksana Tehlivets, Gerhard A Holzapfel","doi":"10.1016/j.actbio.2025.06.003","DOIUrl":"10.1016/j.actbio.2025.06.003","url":null,"abstract":"<p><p>Hyperhomocysteinemia, an elevated level of homocysteine in the blood, is an independent risk factor for atherosclerosis and, more generally, cardiovascular disease. However, its relationship with aortic biomechanics has not been investigated yet. To better understand the influence of elevated homocysteine levels on aortic biomechanics, we propose an animal model in which hyperhomocysteinemia, hypercholesterolemia, and their combination were induced in rabbits by balloon injury of the abdominal aorta, special diets, and intravenous homocysteine injections. The effects of a diet deficient in B vitamins and choline, which are required for homocysteine degradation, a cholesterol-rich diet, their combination, and increased homocysteine concentration are investigated in relation to abdominal aortic biomechanics in rabbits. For this purpose, equibiaxial and non-equibiaxial extension tests were carried out, and the influence of risk factors on the stress-stretch relationship, mechanical anisotropy, and tissue inelasticity is discussed. The mechanical characterization of the tissue was supported by microstructural histological analyses. Our study reveals that deficiency of B vitamins and choline cause aortic stiffening even in the absence of hypercholesterolemia, suggesting a possible independent role in the development of atherosclerosis. Further increasing homocysteine concentration through intravenous injections in rabbits fed B vitamins and choline-deficient diet also results in a stiffer stress response and more pronounced inelastic phenomena with respect to the control group.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318926","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":"Co-assembly of oligo-urethane nanoparticles with defined lipid additives to tailor RNA delivery into cells.","authors":"Suja Shrestha, Elaine Yan, Beining Yang, Aled Blundell, Allen C T Teng, Ryan M Marks, Ronald Cohn, Evgueni Ivakine, Anthony O Gramolini, J Paul Santerre","doi":"10.1016/j.actbio.2025.06.017","DOIUrl":"10.1016/j.actbio.2025.06.017","url":null,"abstract":"<p><p>Developing safe and effective biomaterials to deliver RNA into cells has grown in importance over recent years and has enabled the clinical translation of several gene therapies. Self-assembled oligo-urethane nanoparticles (PNPs) have several advantageous properties, such as (1) mitigating immune cell response in vivo, (2) low cytotoxicity in a broad range of cells, and (3) capable of delivering oligonucleotides or proteins into cells. Here, we were interested in defining unique configurations of PNPs to assess their relative cytotoxicity to human cells, comparing them to a popular commercial lipid system MessengerMax, as some cationic lipids have been found to have associated toxicity, instigating the search for less toxic counterparts. This was then followed by demonstrating the ability of enhanced green fluorescent protein (EGFP) mRNA to be loaded onto the PNPs, and to establish methods to enable the efficient transgene expression in a number of cell types, including Caco-2 and C₂C₁₂ cells which are known to be difficult-to-transfect cells. The addition of small amounts of PEGylated lipid to PNP significantly increased EGFP expression in HEK293T cells, Caco-2 cells and C₂C₁₂ cells at an effective mRNA/PNPs ratio (wt/wt) of 1:40, while the addition of the ionizable cationic lipid, significantly increased EGFP expression in C₂C₁₂ cells and differentiated C₂C₁₂ cells (myofibers) at mRNA/PNPs ratio (wt/wt) of 1:125, while keeping PNPs mass constant to 62.5 μg and changing the mRNA mass. Our study demonstrated that lipid-assisted, PNP-mediated mRNA delivery achieved a high transfection efficiency in terminally differentiated myofibers, paving the way for potential innovative therapeutics, e.g. targeted to muscular dystrophies. STATEMENT OF SIGNIFICANCE: There are reports of diverse delivery agents for RNA, but there is still unmet need for more versatile, and safe delivery vehicles. In this study we demonstrated that when compared to MessengerMax (a lipid-based mRNA transfection reagent), self-assembled oligo-urethane nanoparticle (PNP) showed favorable cell viability. The scope of PNP as a RNA delivery vehicle was extended beyond HEK293T cells by showing transfections into a number of cell types. The addition of select lipids to PNPs, significantly increased EGFP expression in difficult-to-transfect cells: Caco-2 (2.9-fold), C₂C₁₂ (1.4-fold) and differentiated C₂C₁₂ (1.28-fold) cells when compared to PNPs. These findings indicate that select lipid incorporation on PNPs provide a promising strategy to improve the efficacy of RNA therapeutics for diseases in clinical applications.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310928","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}