Acta biomaterialia最新文献

{"title":"Sonosensitizer-doped framework theranostic nanoprobe for enhanced spatiotemporal eradication of helicobacter pylori with photoacoustic imaging guidance.","authors":"Zixuan Zhang, Jiahai Lin, Xinyan Dai, Xinyue Li, Faqi Huang, Shan Qin, Erqun Song, Weihong Tan","doi":"10.1016/j.actbio.2025.06.008","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.06.008","url":null,"abstract":"<p><p>Helicobacter pylori (H. pylori) infection is the leading cause of gastric cancer. Current antibiotic-based H. pylori suppression therapy suffers from low efficacy, drug resistance, and intestinal flora imbalance, which makes an accurate, controllable, and safe H. pylori inhibition strategy urgent. Here, we present a theranostic nanoprobe, UPE@ZH, which integrates sonodynamic therapy and urease inactivation guided by photoacoustic imaging. The UPE@ZH nanoprobe consists of a sonosensitizer and photoacoustic agent, hematoporphyrin monomethyl ether (HMME), doped into a zeolitic imidazolate framework (ZIF-8) and coated with the pH-responsive polymer Ureido-PEG2000-modified polyacrylic resin (UPE). When administered orally to H. pylori-infected mice, the UPE@ZH nanoprobe collapses gradually in the acidic environment of H. pylori infection, while HMME and zinc ion release occur, resulting in the synergistic eradication of H. pylori through HMME-based sonodynamic therapy and zinc ion-based urease inactivation, under the guidance of photoacoustic imaging. This approach offers a promising, efficient, and safe treatment strategy for H. pylori infection with minimized risk of side effects. STATEMENT OF SIGNIFICANCE: Helicobacter pylori (H. pylori) infection has emerged as a growing public health threat. The current triple antibiotic therapy suffers from limited therapeutic efficacy and carries inherent risks of drug resistance and intestinal microbiota dysbiosis. To address these challenges, we developed a novel strategy for photoacoustic imaging-guided antibiotic-free therapeutic based on a theranostic nanoprobe composed of sonosensitizer-doped zeolitic-imidazolate framework, achieving spatiotemporal and enhanced eradication for H. pylori safely. This study makes not only an important contribution to the treatment of H. pylori-related infections but also has general interest to researchers in a broad range of fields, including bacterial eradication, drug delivery, and in vivo imaging.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287437","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":"Divergent effects of premineralization and prevascularization on osteogenesis and vascular integration in humanized tissue engineered bone constructs.","authors":"Sugandha Bhatia, Luke Hipwood, Briony Claxton, Agathe Bessot, Angus Weekes, Kamil Sokolowski, Tomoji Mashimo, Nathalie Bock, Jacqui McGovern","doi":"10.1016/j.actbio.2025.06.019","DOIUrl":"10.1016/j.actbio.2025.06.019","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Osteogenesis (bone formation) and vascularization (blood vessel formation) are two central and interconnected physiological-relevant processes in bone formation. Prevascularization of humanized tissue-engineered bone constructs (hTEBCs) has been proposed to better mimic the human bone microenvironment by enhancing vascular integration and facilitating greater osteogenic capacity. Here, we investigated the effects of premineralization and prevascularization on bone and vasculature development in an ectopic hTEBC model using a scaffold-hydrogel composite approach. Human osteoblast cells (hOBs) were cultured under osteogenic conditions (OM), with or without a 3-day mineralization boost (OM+) period for 4 weeks prior to implantation in vivo in a supporting porous polycaprolactone (mPCL) scaffold. Separately, photocrosslinkable fish gelatin-derived hydrogels placed within supporting mPCL scaffolds showed formation of elongated vascular networks as early as day 3 with in vitro coculture of human umbilical vein endothelial cells (HUVECs) and human bone marrow mesenchymal stem/stromal cells (MSCs). The OM and OM+ cultured constructs were subcutaneously implanted into immunocompromised rats with and without the prevascular hydrogels, resulting in four subgroups: OM, OM+, OM/Vas, and OM+/Vas. Our results demonstrated that the OM+ group led to more rapid osteoinduction and enhanced osteogenic differentiation in vivo with woven bone structure and active remodeling. Conversely, prevascularization (OM/Vas, OM+/Vas groups) led to reduce in vivo bone volume and density but promoted the development of human endothelial networks and successful anastomosis with host vasculature. Our study highlights the distinct contributions of premineralization and prevascularization, where premineralization is critical for robust bone formation and prevascularization enhances vascular integration, providing important insights for advancing the physiological relevance of hTEBC models in animal hosts. STATEMENT OF SIGNIFICANCE: This study demonstrates the development of humanized tissue engineered bone constructs incorporating a vascular niche using a rat. By integrating innovative premineralization and prevascularization techniques within scaffold-hydrogel composites, we show that premineralization accelerates bone formation, while prevascularization promotes endothelial network formation and integration with host vasculature. Photocrosslinkable, low-stiffness LunaGel™ hydrogels enhanced microcapillary-like structure formation and endothelial sprouting in in vitro co-culture. However, by combining osteogenic and vascular cues within a biodegradable composite, this work advances the bone tissue engineering field by creating a model that more accurately reflects the divergent and competing nature of vascularization and bone formation. This platform has broad applicability for studying bone-vascular interactions and may inform strategies to improve the design of biomaterials f","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295479","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 Self-Assembling Chimeric Peptide Gear-Set with \"Three-in-One\" Function for Precision Photodynamic Therapy.","authors":"Qishu Jiao, Tingting Zhang, Shuyao Zhou, Xuan Luo, Shicheng Pei, Yaxin Zheng, Keming Xu, Wenying Zhong","doi":"10.1016/j.actbio.2025.06.015","DOIUrl":"10.1016/j.actbio.2025.06.015","url":null,"abstract":"<p><p>Smart drug delivery systems that activate in response to tumor-specific signals and include real-time monitoring are highly desirable in personalized cancer treatment. Herein, a new chimeric peptide, PpIX-1-DG, is designed with an integrated \"gear set\" mechanism for achieving auto-activation, cascade-amplification and self-reporting features in precision photodynamic therapy. The peptide, comprised of a photosensitizer and a gemcitabine prodrug, self-assembles into nanoparticles in physiological condition. Upon cellular uptake, nanoparticles specifically respond to elevated GSH levels in cancer cells to release gemcitabine, thereby exerting its chemotherapeutic effect for initiating apoptosis and activating caspase-3-the first \"auto-activation\" gear. Next, caspase-3 catalyzes the production of photosensitive PpIX-1, resulting in elevation of intracellular ROS in A549 cells, thereby inducing mitochondrial dysfunction and more apoptosis upon photoirradiation. This process elevates caspase-3 levels and activates additional photosensitizers, marking the second \"cascade amplification\" gear. Intravenous administration of PpIX-1-DG alongside photoirradiation shows enhanced antitumor efficacy and minimal systemic toxicity. Notably, the fluorescence of PpIX-1-DG activated by caspase-3 facilitates real-time monitoring, enabling the third \"self-reporting\" gear for therapeutic outcome tracking in vitro and in vivo. Together, this \"three-in-one\" strategy enables precision photodynamic therapy and synchronous therapeutic monitoring, holding great potential in the realm of cancer nanomedicine. STATEMENT OF SIGNIFICANCE: This study presents a self-assembled chimeric peptide nanoplatform (PpIX-1-DG NPs) that integrates a 'three-in-one' mechanism, enabling auto-activation, cascade amplification, and self-reporting functions for precision photodynamic therapy while allowing real-time monitoring of treatment efficacy. In GSH-rich tumor microenvironment, the peptide specifically releases gemcitabine, which triggers the activation of caspase-3. This enzyme cleaves a DEVD linker in the peptide molecule, thereby activating the photosensitive PpIX-1. The activated PpIX-1 then generates reactive oxygen species (ROS) upon photoirradiation, triggering more cells undergoing apoptosis and ferroptosis. Meanwhile, the fluorescence emitted from activated PpIX-1 allows dynamic tracking of treatment efficacy. We believe this approach offers a new paradigm for improving treatment outcomes and therapeutic monitoring over a variety of diseases.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287436","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":"Recent advances in 3D models of the nervous system for neural regeneration research and drug development.","authors":"Hui Zhu, Cong Yao, Zhengqi Xu, Guojin Shang, Jianhua Peng, Huangfan Xie, Tingyu Qian, Zhennan Qiu, Lidia Maeso, Mao Mao, Yucheng Liao, Yong Jiang, Dichen Li, Gorka Orive, Aldo R Boccaccini","doi":"10.1016/j.actbio.2025.06.013","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.06.013","url":null,"abstract":"<p><p>The development of drugs for nervous diseases poses distinctive difficulties owing to the incomplete understanding of the physiology and complex pathogenesis of the multifaceted central (CNS) and peripheral (PNS) nervous systems. Conventional animal tests and in vitro two-dimensional (2D) cell cultures fail to reproduce the sophisticated structure of natural human tissues, hindering the new drug discovery process. The emerging three-dimensional (3D) neural tissue models, including organoids, organ-on-chips and 3D-printed neural scaffolds, can provide an improved reproduction of the critical features, structural complexity, biological functions, dynamic circulation micro-environment and cell-matrix/cell interactions of the nervous systems. This review examines state-of-the-art 3D models for neural physiology/pathology, emphasizing their drug development applications. Fundamental advantages of various in vitro 3D neural models for investigating the mechanisms of nerve regeneration and disorders in both the CNS and PNS are compared in terms of the different modeling techniques. In addition, the applications of 3D neural models in drug development are summarized covering a range of areas such as disease modeling for basic research, pharmacokinetic and pharmacodynamic testing for drug screening and drug safety evaluation. Furthermore, current challenges and future outlook of biomimetic models and the existing bottlenecks hindering their successful translation into clinical use are discussed. STATEMENT OF SIGNIFICANCE: This review highlights the groundbreaking potential of 3D neural models-organoids, organ-on-chips, and 3D-printed scaffolds-to revolutionize neurological research and drug development. Unlike conventional methods, these models replicate the intricate structure and function of human nervous systems, enabling precise study of diseases like Alzheimer's, spinal injuries, and brain tumors. By synthesizing recent advancements, the review compares techniques, their applications in drug screening and personalized medicine, and addresses challenges in model accuracy and scalability. Bridging neuroscience, engineering, and pharmacology, this work provides a roadmap for researchers to innovate therapies. Its insights are critical for accelerating drug discovery and improving treatment outcomes, making it essential for scientists and clinicians tackling neurological disorders.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259539","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":"Engineering of bioprosthetic heart valves with synergistic zwitterionic surface modification and zirconium cross-linking for improved biocompatibility and durability.","authors":"Kaijun Li, Qinsheng Hu, Ling Wang, Chengcheng Wu, Li Yang, Gongyan Liu, Yunbing Wang","doi":"10.1016/j.actbio.2025.06.010","DOIUrl":"10.1016/j.actbio.2025.06.010","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Bioprosthetic heart valves (BHVs) are frequently utilized in surgeries for heart valve replacement to address valvular heart disease (VHD). Despite their widespread use, BHVs still face challenges in clinical applications, such as thrombosis, calcification, immune responses, poor re-endothelialization, infection, component degradation, and mechanical failure, which are largely due to the heterogeneous cross-linking effects. To address these issues, we propose a synergistic engineering strategy based on sequential zwitterionic surface modification and zirconium cross-linking to improve the biocompatibility and durability of BHVs. After surface modification via ring-opening reactions of zwitterionic epoxy copolymers (PGSB) on collagen fibers of decellularized porcine pericardium (D-PP), the zwitterionic PGSB significantly promoted the uniform transfer of zirconium ions (Zr&lt;sup&gt;4+&lt;/sup&gt;) and further coordinated with Zr&lt;sup&gt;4+&lt;/sup&gt; to achieve homogeneous cross-linking between collagen fibers. Compared to conventional glutaraldehyde (GA)-cross-linked PP, PGSB/Zr-PP showed enhanced anti-thrombotic performance, attenuated immune rejection, accelerated endothelialization, and over 95 % reduction in calcification after 90 days of subcutaneous implantation, collectively indicating improved biocompatibility. Furthermore, this homogeneously cross-linked PGSB/Zr-PP exhibited undetectable component degradation and simultaneous improvements in both strength and toughness, all of which are essential for improving the durability of BHVs. Intriguingly, the zwitterionic sulfobetaine groups could be converted into bactericidal quaternary ammonium groups upon coordination with Zr&lt;sup&gt;4+&lt;/sup&gt;, resulting in strong antibacterial and anti-biofilm activities beneficial for preventing life-threatening prosthetic valve endocarditis. More importantly, PGSB/Zr-PP met the ISO 5840-3 standards required for BHV applications in terms of hydrodynamic performance and 200-million-cycle durability. These results demonstrate that PGSB/Zr-PP would be a promising alternative to GA-cross-linked BHVs. STATEMENT OF SIGNIFICANCE: Mainstream glutaraldehyde-cross-linked BHV face persistent clinical challenges, including thrombosis, calcification, immune response, poor re-endothelialization, infection, component degradation, and mechanical failure. Although various non-glutaraldehyde cross-linkers have been investigated, few strategies effectively address these challenges due to the heterogeneous nature of cross-linking. Herein, we present a synergistic engineering strategy based on sequential zwitterionic surface modification and zirconium cross-linking. This strategy produces homogeneously cross-linked BHVs with comprehensive improvements in anti-thrombogenicity, immune compatibility, endothelialization, resistance to calcification and infection, enzymatic stability, and mechanical strength. Notably, the aortic BHV fabricated via this method met the ISO 5840-3 standards for hydrodyna","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259537","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":"Property-tailoring chemical modifications of hyaluronic acid for regenerative medicine applications.","authors":"Peiling Huang, Li Wang, Boon Chin Heng, Ismaeil Haririan, Qing Cai, Zigang Ge","doi":"10.1016/j.actbio.2025.06.014","DOIUrl":"10.1016/j.actbio.2025.06.014","url":null,"abstract":"<p><p>Hyaluronic acid (HA) as well as HA-based materials are widely applied in regenerative medicine due to their good biocompatibility, bioactivity and amenability to chemical modifications. Although the reactive sites and associated reaction types of HA have been summarized previously to guide chemical modification and synthesis of HA-based materials, the relationship between chemical modifications and HA-based material properties has not yet been discussed. In this review, the key properties of HA-based materials required for regenerative medicine in various tissues and organs including skin, bone, cartilage, heart and cornea are summarized and various chemical modification strategies aimed at achieving these properties are discussed. Versatile HA-based materials can be tailored through crosslinking and conjugation, as well as regulating the internal bonding types and degrees of modification. We also provide a comparative analysis of commonly used HA-based materials modification methods and discuss their practical advantages, limitations, and the current status of clinical translation. Even with significant progress already achieved, there is still a long way to go in precisely fine-tuning chemical modifications, balancing functionality and practicality, as well as in understanding their interactions with the diverse array of cells and tissues in vivo. This review bridges tissue-specific property demands with chemical design strategies. We believe that this demand-driven framework provides a practical and accessible guide for researchers intending to design HA-based materials with targeted regenerative capabilities. STATEMENT OF SIGNIFICANCE: This review critically examines hyaluronic acid (HA) and HA-based materials in regenerative medicine applications, focusing on the key properties required for applications in specific tissues such as skin, bone, cartilage, heart, and cornea, as well as the associated chemical modification strategies. While design strategies for HA-based materials have been studied in the past, the relationship between chemical modifications and the resulting material properties remains under-explored. This review thus addresses this gap by systematically categorizing various chemical modification strategies that have been tailored to different material property requirements, providing a comparative analysis of commonly used chemical modification methods, and discussing current clinical challenges and future directions of HA-based materials. By linking material properties to chemical modification strategies, this review thus provides a comprehensive guide for researchers and offers valuable insights for advancing the applications of HA-based materials in regenerative medicine.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259538","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":"Collagen Glycation-Mediated Mechanical Stress Aggravates Ischemia-Reperfusion injury.","authors":"Jing Yang, Yixuan Li, Xiaoxiao Fan, Tong Zhang, Junhai Pan, Si Shen, Cheng Zhong, Duguang Li, Yi Zhang, Guoqiao Chen, Wei Ji, Shuqi Wu, Shengxi Jin, Xiaolong Liu, Qiming Xia, Peilin Yu, Wei Yang, Yang Gao, Liangfei Tian, Hui Lin","doi":"10.1016/j.actbio.2025.06.012","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.06.012","url":null,"abstract":"<p><p>Ischemia-reperfusion (IR) injury is a grave concern because of its substantial risk of organ failure in organ transplantation. Understanding its mechanism is essential for exploring potential management strategies to alleviate IR injury. In this study, we investigate the development of IR injury from a biomechanical perspective. Our results reveal a significant increase in tissue stiffness in IR- affected areas, driven by extracellular matrix crosslinking through collagen glycation. A stiffened matrix induces mechanical stretch, leading to excessive intracellular force transmission, which triggers apoptosis and worsen tissue injury. In livers with substantial collagen accumulation, such as those with fibrosis or aging, ischemia-reperfusion results in increased collagen glycation, pronounced abnormal mechanical signaling, and severe damage. Importantly, our data further demonstrate that intercepting mechanical force transduction effectively alleviate hepatic IR injury. This work deepens the understanding of IR development from a biomechanical perspective and provides new insights into future IR injury management. STATEMENT OF SIGNIFICANCE: Transplantation is a common treatment for various end-stage diseases. However, ischemia reperfusion injury during transplant procedures poses a risk of organ failure in patients. Unraveling the molecular mechanisms behind this process is of significant clinical importance. Our study innovatively demonstrates that ischemia reperfusion leads to an increase in extracellular matrix stiffness, which induces mechanical stress and promotes cell death, thereby exacerbating ischemia reperfusion injury. Inhibition of abnormal mechanical signaling was found to alleviate this injury, this offered a new therapeutic approach for managing ischemia reperfusion in the future.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251267","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":"Synergistic reversal of inflammation-mediated degeneration in intervertebral discs: Phenylboric acid-grafted hyaluronic acid hydrogel as an anti-oxidative vehicle for Timp-3 delivery and promotion of extracellular matrix synthesis.","authors":"Yan Li, Yuxiang Zhang, Shuqin Wang, Xiaojing Ma, Chengxin Dai, Yifan Wang, Chenyi Ye, Sunwen Pan, Changyou Gao, Weixu Li","doi":"10.1016/j.actbio.2025.06.011","DOIUrl":"10.1016/j.actbio.2025.06.011","url":null,"abstract":"<p><strong>Background: </strong>Intervertebral disc degeneration (IDD) is intricately linked to the aging process, wherein reactive oxygen species (ROS) and inflammatory responses markedly contribute to matrix degradation and hyperplasia. Injectable antioxidant hydrogels loaded with pharmacological agents hold immense promise for clinical translation in early intervention of IDD. Our previous study revealed that the tissue inhibitor of metalloproteinase-3 (TIMP3) is a pivotal regulator of matrix remodeling and inflammation.</p><p><strong>Results: </strong>We developed a biodegradable ROS-responsive hydrogel functionalized with phenylboronic acid (R-gel) as a controlled release carrier of TIMP3 (R-gel-TIMP3). R-gel-TIMP3 effectively scavenged ROS and provided sustained TIMP3 delivery, thereby attenuating inflammation-driven disc degeneration. In vitro, R-gel-TIMP3 exhibited negligible cytotoxicity, reduced ROS levels in the nucleus pulposus cells, and alleviated cellular senescence and apoptosis. In vivo, it decreased ROS accumulation, inflammatory M1 macrophages, matrix degradation, and neovascularization, significantly ameliorating IDD pathology.</p><p><strong>Conclusion: </strong>The synergistic action of ROS-responsive TIMP3 delivery markedly amplified the therapeutic efficacy against IDD, underscoring the therapeutic potential of R-gel-TIMP3 in IDD management.</p><p><strong>Statement of significance: </strong>1 We synthesized an injectable bioactive ROS-responsive hydrogel as an anti-oxidative vehicle for TIMP3 protein delivery. 2 The hydrogel enabled sustained release of TIMP-3 in situ and acted as an efficient ROS scavenger to protect NPs against oxidative stress. 3 This treatment could effectively intervene in the progression of IDD from early stage, promote extracellular matrix synthesis, and ultimately reduce IDD in a rat model.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251231","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-delivery of neurotrophic factors and a zinc chelator substantially increases retinal ganglion cell survival and axon protection in the optic nerve crush model.","authors":"Huynh Quang Dieu Nguyen, Mi-Hyun Nam, Jozsef Vigh, Joseph Brzezinski, Lucas Duncan, Daewon Park","doi":"10.1016/j.actbio.2025.06.007","DOIUrl":"10.1016/j.actbio.2025.06.007","url":null,"abstract":"<p><p>Traumatic optic neuropathies lead to retinal ganglion cell (RGC) death and axonal degeneration, primarily due to disrupted neurotrophic factor (NTF) supply from the brain and a neurotoxic cascade, potentially mediated by elevated retinal Zn²⁺ levels. Ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) are two major NTFs known to support RGC survival and axon protection. Dipicolylamine (DPA), a Zn²⁺ chelator with high selectivity and affinity, offers a strategy to reduce excess Zn²⁺. To achieve sustained NTF delivery and Zn²⁺ reduction, we developed sulfonated poly(serinol hexamethylene urea) nanoparticles (S-PSHU NPs) co-loaded with CNTF, BDNF, and DPA. In vitro release studies demonstrated sustained release of CNTF and BDNF for up to 8 weeks and DPA for up to 4 weeks. In a rat optic nerve crush (ONC) model, DPA-loaded S-PSHU NPs showed dose-dependent elimination of retinal Zn²⁺. Additionally, in primary RGC culture, RGC activity and axon growth correlated with CNTF and BDNF dosage. In vivo, NTF-DPA-loaded S-PSHU NPs significantly enhanced RGC survival and axon protection post-ONC, as evidenced by cholera toxin subunit B (CTB)-labeled axons in the central visual centers of the brain, including the suprachiasmatic nucleus, lateral geniculate nucleus, and superior colliculus. STATEMENT OF SIGNIFICANCE: • Co-delivery of neurotrophic factors (NTFs: CNTF and BDNF) and a zinc chelator (dipicolylamine, DPA) promotes retinal ganglion cell (RGC) axon survival and protection. • Sustained release of NTFs for up to 8 weeks and DPA for up to 4 weeks. • DPA-loaded nanoparticles effectively eliminate excess retinal zinc after optic nerve injury. • NTF-DPA-loaded nanoparticles significantly improve RGC survival and axon protection in a rat optic nerve crush model.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251266","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":"Biodegradable Zn-xY alloys with enhanced osteogenesis and angiogenesis effects for bone implant applications.","authors":"Shimin Liang, Shaokang Du, Yufeng Zheng, Dandan Xia, Yongsheng Zhou","doi":"10.1016/j.actbio.2025.05.048","DOIUrl":"10.1016/j.actbio.2025.05.048","url":null,"abstract":"<p><p>Biodegradable zinc-based alloys have gained significant attention in the biomedical field due to their favorable degradability, but challenges remain in enhancing their mechanical properties and biocompatibility. As promising candidates for bone implant materials, improving osteogenic differentiation, angiogenesis and antibacterial properties is crucial. In this study, Zinc-xYttrium (Zn-xY, x = 0.1, 0.6, 1.0 and 2.0 at.%) alloys were developed, and their mechanical properties, degradation behavior, cytocompatibility, osteogenic activity, angiogenic potential and antibacterial properties were systematically evaluated. Specifically, Zn-2.0Y exhibited the highest mechanical strength, with a tensile strength (UTS) of 230 MPa, yield strength (YS) of 170 MPa, and elongation at break (ER) of approximately 16%. In terms of degradation, Zn-2.0Y demonstrated the slowest degradation rate. Additionally, this alloy significantly enhanced osteogenic differentiation and mineralization of human bone marrow-derived mesenchymal stem cells (hBMSCs) and promoted migration and angiogenic activity in human umbilical vein endothelial cells (HUVECs). Moreover, this alloy demonstrated far better antibacterial properties than pure Zn. In vivo rat femoral implantation studies further confirmed that Zn-2.0Y promoted bone integration. Moreover, the study revealed and validated that Zn-2.0Y enhances osteogenic and angiogenic activities through the PI3K/AKT signaling pathway. These findings highlight Zn-2.0Y as a promising biodegradable material for bone implant applications. STATEMENT OF SIGNIFICANCE: The development of advanced biodegradable bone implant materials is crucial for addressing complex challenges in bone repair. This study investigates Zinc-xYttrium (Zn-xY, x = 0.1, 0.6, 1.0 and 2.0 at.%) alloys, focusing on Zn-2.0Y, which exhibits tensile strength >230 MPa, yield strength ∼170 MPa, and elongation at break ∼16%. The degradation rate of Zn-xY alloys decreases with increasing Y content, with Zn-2.0Y showing the lowest rate of 45 µm/y. In vitro and in vivo studies demonstrate that Zn-2.0Y promotes osteogenesis and angiogenesis by activating the PI3K/AKT signaling pathway. These findings highlight Zn-2.0Y as a promising biodegradable material for bone repair.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251265","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}