Acta biomaterialia最新文献

{"title":"Redox-Responsive Dendritic Copolymer-Drug Conjugates Enhance Therapeutic Mitophagy Through Coordinated Microtubule Destabilization for Synergistic Triple-Negative Breast Cancer Therapy.","authors":"Guohao Liu, Bing Wang, Ping Chen, Zhiqian Li, Xinying Cheng, Qiyong Gong, Kui Luo","doi":"10.1016/j.actbio.2025.06.038","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.06.038","url":null,"abstract":"<p><p>Application of microtubule-targeting agents (MTAs) for triple-negative breast cancer (TNBC) is hampered by their limited efficacy and strong systemic toxicity. Herein, we reported dendritic copolymer-drug conjugates to synergistically disrupt microtubule dynamics and induce therapeutic mitochondrial autophagy (mitophagy), thus enhancing therapeutic efficacy of MTAs. Paclitaxel (PTX) and 2-methoxyestradiol (2ME) were conjugated to glutathione-stimuli responsive dendritic copolymers, resulting in DDS-PTX and DDS-2ME, respectively. PTX and 2ME were tumor-specifically released from DDS-PTX and DDS-2ME, and simultaneously acted on microtubule polymerization and depolymerization, respectively. Dual perturbation of microtubules triggered catastrophic microtubule network collapse, prolonged mitotic arrest and amplified mitochondrial stress. Mechanistically, severe mitotic stress activated the PINK1/Parkin pathway, driving excessive mitophagy and caspase-dependent apoptosis. In a murine TNBC model, treatment with combined DDS-PTX and DDS-2ME resulted in a tumor inhibition rate of 95.01%, and the median survival was significantly extended compared to monotherapies with DDS-PTX or DDS-2ME. This combined formulation also remarkably reduced side effects of free PTX and 2ME. Mitophagy-mediated apoptotic amplification was explored as a therapeutic paradigm in this study to bridge cytoskeletal disruption with organelle-level vulnerability for enhanced tumor therapy. STATEMENT OF SIGNIFICANCE: Distinct redox-responsive dendritic copolymer-drug conjugates (DDS-PTX and DDS-2ME) were constructed to deliver paclitaxel and 2-methoxyestradiol for synergistic triple-negative breast cancer therapy. Tumor-specific drug release enabled spatiotemporal coordination of microtubule stabilization and depolymerization, thus inducing catastrophic microtubule fragmentation, prolonged mitotic arrest, and amplified mitochondrial stress. These effects subsequently triggered PINK1/Parkin-mediated therapeutic mitophagy and caspase-dependent apoptosis, achieving a 95.01% tumor suppression rate and extending median survival to 56 days in murine models. Notably, the conjugates significantly reduced systemic toxicity compared to free drugs while maintaining hemocompatibility and organ safety. By integrating molecular-scale tumor microenvironment (TME) responsiveness with cytoskeletal-organelle crosstalk, this work establishes a mechanistically driven paradigm to amplify subcellular stress responses, offering a transformative strategy for refractory cancers with enhanced efficacy and safety.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487418","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":"Multilayered Trabecular Meshwork for Dynamic In Vitro Studies in Glaucoma Research.","authors":"Magdalena Z Gładysz, Micaela Gaspar Gonçalves Fernandes, Xiaopeng Li, Marcus Koch, Frendion Marchena, Anno Hofman, Mariska de Graaf, Justina Clarinda Wolters, Marleen Kamperman, Anika Nagelkerke, Małgorzata K Włodarczyk-Biegun","doi":"10.1016/j.actbio.2025.06.035","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.06.035","url":null,"abstract":"<p><p>Glaucoma, an eye disease causing incremental vision loss, currently has no cure. Its primary cause is the malfunction of the trabecular meshwork (TM), a multilayered tissue in the eye responsible for draining aqueous humor (AH) from the anterior chamber. TM clogging increases outflow resistance, elevates intraocular pressure (IOP), and damages optic nerves, leading to irreversible blindness. Existing in vitro TM models are suboptimal, as they lack the hierarchical structure of the TM. This article introduces a dynamic in vitro TM model, featuring a multilayered scaffold architecture 3D printed via melt electrowriting (MEW), and integrated with a flow system that enables continuous pressure monitoring during perfusion at native flow rates. Printed scaffolds supported the growth of primary adult human TM cells that grew on top and between the fibers. Cellularized scaffolds were tested under static and dynamic conditions. Over 3-5 days, pressure monitoring showed increased outflow resistance due to cell proliferation. Proteomic analysis revealed distinct changes in protein expression related to protein synthesis and respiration of cells grown under flow. Lat-B administration resulted in decreased pressure values and depolymerized actin filaments. These findings suggest that the proposed model is a promising alternative for in vitro glaucoma drug testing. STATEMENT OF SIGNIFICANCE: This study introduces a model of the trabecular meshwork (TM), a tissue in the eye involved in glaucoma, a common eye disease that currently has no cure. Using 3D printing, we created a multilayered scaffold that mimics the structure and function of the human TM. This allows us to study how cells behave and how drugs work under realistic conditions. Unlike existing models, ours accurately replicates all three layers of the TM, providing an advanced dynamic platform for glaucoma research. This innovation could help develop new treatments by offering a more reliable model for testing drugs and understanding how glaucoma works, making a significant impact on eye research.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478197","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":"Spatiotemporal self-reinforcing hydrogel spray with antibacterial and anti-inflammatory properties for accelerated diabetic wound healing.","authors":"Shihua Mao, Zengzhe Liu, Wenli Yu, Wenzhe Zhang, Pingan Lin, Shuaibing Wang, Jintao Yang, Guoli Yang","doi":"10.1016/j.actbio.2025.06.036","DOIUrl":"10.1016/j.actbio.2025.06.036","url":null,"abstract":"<p><p>Sprayable hydrogels present an effective strategy for treating diabetic wounds, offering ease of application and good conformity to irregularly shaped wound sites. Nonetheless, their practical use remains significantly restricted by insufficient mechanical robustness and limited multifunctionality. Therefore, developing an approach to design sprayable hydrogel that simultaneously enhances mechanical strength, broadens functional capabilities, and ensures optimal wound adaptability is critically needed. In this work, an innovative approach integrating spatiotemporal self-strengthening and sprayability is proposed for the development of hydrogel-based wound dressings. This functionality is achieved through the synergy of rapid amidation and a gradual ring-opening reaction, equipping the hydrogels with both good wound adaptability and superior mechanical stability. The incorporation of polydopamine nanoparticles (PDA NPs) enables the creation of multifunctional therapeutic hydrogels specifically designed for chronic diabetic wound treatment. The hydrogel can be effortlessly sprayed onto wounds, progressively enhance their mechanical properties, and exhibit a combination of potent antibacterial activity, efficient reactive oxygen species (ROS) scavenging, strong bioadhesion, and outstanding biocompatibility, ultimately accelerating the diabetic wound healing process. We believe that sprayable hydrogels with these advanced properties will provide valuable insights into hydrogel-based wound dressings and expand the biomedical applications of bioinspired hydrogels. STATEMENT OF SIGNIFICANCE: Sprayable hydrogels present an effective strategy for treating diabetic wounds, offering ease of application and good conformity to irregularly shaped wound sites. Nonetheless, their practical use remains significantly restricted by insufficient mechanical robustness and limited multifunctionality. Herein, an approach integrating spatiotemporal self-strengthening and sprayability is proposed for the development of hydrogel-based wound dressings. Furthermore, we have developed sprayable hydrogel dressings with spatiotemporal self-strengthening, antibacterial and anti-inflammatory properties, consisting of double-network hydrogel and polydopamine nanoparticles (PDA NPs) as a multitargeted therapeutic system for chronic diabetic wound healing. We believe that this sprayable hydrogels will provide valuable insights into hydrogel-based wound dressings and expand the biomedical applications.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144369704","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-based therapy for type 1 diabetes: from immuno-intervention to insulin delivery.","authors":"Huiwen Pang, Zhuo Chen, Felicity Y Han","doi":"10.1016/j.actbio.2025.06.016","DOIUrl":"10.1016/j.actbio.2025.06.016","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is a chronic autoimmune disease in which the immune system mistakenly attacks and destroys insulin-producing β-cells in the pancreas, causing an absolute insulin deficiency. While traditional treatments, such as insulin replacement therapy, can alleviate symptoms, they fail to halt disease progression fundamentally. Recent advancements in nanotechnology have shown significant progress in treating T1D, particularly in restoring immune tolerance and enabling precise drug delivery. These innovative nano-based therapies allow researchers to better regulate immune responses and protect the remaining β-cell function. Additionally, breakthroughs in insulin delivery using nano-based systems, including oral, transdermal, and glucose-responsive insulin release delivery systems, have provided new avenues for improving glycemic control in T1D patients. Here by exploring the pathogenesis of T1D and the importance of immune tolerance with the intervention of nanotechnology, this review summarizes nano-based innovative strategies in immune intervention, including antigen, antibody and gene therapy, as well as nano-based insulin delivery systems including the to-date achievement and related challenges remaining. Developing more effective nano-based therapeutic approaches for T1D holds big promise. STATEMENT OF SIGNIFICANCE: T1D remains a significant clinical challenge due to its autoimmune nature and the lifelong dependence on insulin therapy. Traditional treatments manage symptoms but do not address the underlying immune dysfunction. This review underscores the transformative potential of nanotechnology in T1D treatment by integrating immune modulation and advanced insulin delivery. Nano-based immunotherapies aim to restore immune tolerance and preserve β-cell function, tackling the root cause of the disease. At the same time, precise insulin delivery systems offer improved glycemic control with reduced patient burden. By presenting current progress and remaining challenges, this review highlights how nano-based therapies could revolutionize T1D management, offering not only better disease control but also a pathway toward long-term remission and potentially a cure.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammatory itaconate-loaded, cell-adhesive peptide-conjugated artificial small diameter vascular grafts for blood vessel regeneration.","authors":"Yu Gao, Yuwei Li, Nan Jiang, Rui Gao, Yushan Zhang, Zujian Feng, Chuangnian Zhang, Lianyong Wang, Weiwei Wang, Deling Kong, Pingsheng Huang","doi":"10.1016/j.actbio.2025.06.034","DOIUrl":"10.1016/j.actbio.2025.06.034","url":null,"abstract":"<p><p>The adverse remodeling is a major cause of the low patency rate of artificial small-diameter vascular grafts (SDVGs), preventing clinical application in vascular disease treatment. To inhibit intimal hyperplasia and achieve rapid endothelialization after implantation, we designed PLCL/OI@REDV grafts composed of poly (l-lactide-co-ε-caprolactone) (PLCL) electrospinning tubes loaded with anti-inflammatory 4-octyl itaconate (OI) and coated with cell-adhesive REDV peptide. PLCL/OI@REDV grafts showed a micro-scale fibrous crosslinked structure and a burst pressure higher than 1600 mmHg. Then, PLCL/OI@REDV membranes were verified to inhibit the smooth muscle cell (SMC) proliferation via the release of OI and to promote the adhesion and proliferation of endothelial cells (ECs) due to REDV modification, contributing to the competitive growth of ECs. Furthermore, it was confirmed that OI showed significant suppression of M1 macrophage polarization, thereby reducing the production of inflammatory factors and reactive oxygen species, which in turn maintained the viability and function of ECs. Subcutaneous implantation in rats demonstrated that PLCL/OI@REDV membranes elicited lower levels of inflammatory and fibrotic reactions than PLCL membranes. In rat abdominal aorta replacement models, compared with PLCL grafts, PLCL/OI@REDV grafts were found to down-regulate the M1 macrophage expression, inhibit excessive SMC proliferation, and promote endothelialization, collectively improving vascular regeneration and patency. In summary, PLCL/OI@REDV represents a promising artificial vascular graft with endogenous regeneration ability. STATEMENT OF SIGNIFICANCE: Small-diameter artificial vascular grafts (SDVGs) hold broad application prospects in clinical hemodialysis, and peripheral or coronary artery bypass grafting. However, they are faced with a high risk of thrombosis and stenosis caused by inflammation, intimal hyperplasia and slow endothelialization. In this study, we prepared a SDVG, PLCL/OI@REDV, composed of poly (l-lactide-co-ε-caprolactone) (PLCL) electrospinning tube loaded with anti-inflammatory and anti-fibrotic 4-octyl itaconate, and coated with cell-adhesive peptide REDV. PLCL/OI@REDV collectively reduced inflammation by suppressing M1 macrophage polarization, inhibited intimal hyperplasia by decreasing the excessive smooth muscle cell proliferation, and facilitated endothelialization via improving endothelial cell adhesion and proliferation, thus increasing patency rate. Therefore, PLCL/OI@REDV is a promising SDVG with endogenous regenerative ability.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Borosilicate bioactive glass 3D fibrous matrices with increased borate content stimulate healing cascades in chronic wounds.","authors":"Xingchen Zhao, Dong Zhai, Gavin Jell, Chengtie Wu, Huiling Gao, Julian R Jones","doi":"10.1016/j.actbio.2025.06.033","DOIUrl":"10.1016/j.actbio.2025.06.033","url":null,"abstract":"<p><p>Diabetic wound regeneration is hindered by dysfunctional extracellular matrix (ECM) formation, impaired angiogenesis and prolonged inflammation. We report the first borosilicate bioactive glass (BG) nanofiber wound matrices with borate content exceeding 2 mol%, achieving up to 70 mol% borate, by optimizing modified sol-gel electrospinning parameters. The resultant 3D matrices mimic the morphology of extracellular matrix fibers with homogeneous fiber diameters of 100-300 nm that can biodegrade with the release of therapeutic calcium ions and borate and silicate species. The focus was investigation of the impact of borate content on cellular response in vitro to identify the optimal borosilicate composition; 55SiO₂-30CaO-15B₂O₃ (mol%, 55S30C15B) matrix promoted the greatest expression of vascular endothelial growth factor and basic fibroblast growth factor by fibroblasts and led to the highest stimulation metabolic activity, protein expression and migration of endothelial cells. Our in vivo study (mouse diabetic model) confirmed the efficacy of 55S30C15B wound matrix in improving wound closure, anti-inflammatory response, angiogenesis, tissue granulation (α-SMA), and collagen deposition, while elaborating the distinct roles of borates and nanofiber structure. All evidence suggests that our matrices exhibit great potential for diabetic wound regeneration. STATEMENT OF SIGNIFICANCE: We developed a new scaffold for wound healing; the first borosilicate BG nanofiber (100 -300 nm) mats with borate content in excess of 2 mol%, with boron content of up to 70 mol%. We identified the influence of borate dose delivered by the fibers on both fibroblasts and endothelial cells. Efficacy of the ECM-mimicking scaffold structure was shown across all stages of the wound healing cascade in an in vivo model.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340772","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":"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":"&lt;p&gt;&lt;p&gt;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&lt;sub&gt;ax&lt;/sub&gt; = 1.9 ± 0.1 kPa, μ&lt;sub&gt;tra&lt;/sub&gt; = 1.3 ± 0.1 kPa, E&lt;sub&gt;ax&lt;/sub&gt; = 5.6 ± 0.4 kPa, and E&lt;sub&gt;tra&lt;/sub&gt; = 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}