Acta biomaterialia最新文献

{"title":"Hybrid cell-membrane-coated biomimetic nanoparticles for targeted noninvasive intervention in early diabetic retinopathy.","authors":"Fan Yang, Lu Zhang, Zhenping Li, Mengting Zhang, Xiaowen Deng, Difang Sun, Meng Jiang, Shushu Gui, Yufei Du, Shurong Guo, Qihang Zhou, Zongyi Zhan, Haijun Gong, Yichi Zhang, Yiming Zhou, Yuanyuan Su, Yuqing Lan","doi":"10.1016/j.actbio.2025.09.023","DOIUrl":"10.1016/j.actbio.2025.09.023","url":null,"abstract":"<p><p>Diabetic retinopathy (DR), a diabetes mellitus-induced ocular complication, demands non-invasive and effective early interventions to halt disease progression. Here, we developed biomimetic hybrid nanoparticles ([RBC-EC]-NPs) by coating fused membranes derived from red blood cells (RBC) and retinal endothelial cells (EC) on poly (lactic-co-glycolic acid) (PLGA) cores. Optimizing the membrane-to-PLGA ratio to 1:2 yielded stable nanoparticles that preserved critical membrane proteins, including CD47 (for immune evasion) and vascular endothelial cadherin (for endothelial targeting). The dual-coating strategy synergistically enhanced retinal endothelial targeting, suppressed pathological EC migration, and prolonged systemic circulation. In a STZ-induced diabetic rat model, intravenously administered [RBC-EC]-NPs selectively accumulated in retinal vasculature, significantly downregulating vascular endothelial growth factor expression, mitigating vascular leakage, thereby reducing formation of acellular capillary. Transcriptomic analysis revealed nanoparticle-mediated restoration of lysosomal function, lipid metabolism, and tumor necrosis factor-associated inflammatory pathways. Notably, systemic treatment also ameliorated dyslipidemia without inducing hematological or hepatic toxicity. Comprehensive biosafety evaluations confirmed the absence of acute tissue damage. Together, these findings demonstrated that [RBC-EC]-NPs could represent a potent and targeted nanotherapeutic platform for early-stage DR intervention, combining dual-cell membrane advantages with high biocompatibility. STATEMENT OF SIGNIFICANCE: Diabetic retinopathy (DR) remains a leading cause of blindness, and current treatments are largely invasive and limited to late stages. Here, we developed hybrid red blood cell-endothelial cell membrane-coated nanoparticles ([RBC-EC]-NPs) as a minimally invasive intravenous therapy. These biomimetic NPs uniquely combine endothelial targeting and immune evasion, enabling selective retinal vascular accumulation. Mechanistically, [RBC-EC]-NPs reduced VEGF overexpression, restored lysosomal-autophagy function, suppressed inflammation, and rebalanced lipid metabolism, thereby alleviating vascular leakage, preserving retinal microcirculation, and improving systemic lipid profiles in diabetic rat models. This study demonstrates the potential of [RBC-EC]-NPs as a safe, multifunctional therapeutic platform that targets the metabolic and vascular pathogenesis of early DR, offering a promising alternative to current intravitreal interventions.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093229","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":"Programmable DNAzyme walkers on gold nanoplatforms: From rational design to bioimaging/biosensing breakthroughs.","authors":"Keqing Wang, Wenjing Zhu, Xin Li, Guixia Ling, Peng Zhang","doi":"10.1016/j.actbio.2025.09.020","DOIUrl":"10.1016/j.actbio.2025.09.020","url":null,"abstract":"<p><p>DNA walkers play a strategic role in precision medicine for applications such as single-cell analysis and tumor microenvironment modulation, yet face bottlenecks in stability, efficiency, and physiological adaptability. A DNA walker primarily comprises a walking strand, track, and driving force. DNAzyme-driven walkers achieve autonomous movement via enzymatic catalysis, eliminating reliance on external energy. The AuNP-DNAzyme synergy overcomes bottlenecks via surface plasmon resonance, thiol chemistry, and nanoconfinement for signal enhancement, dense DNA modification, and enzyme stabilization. Compared to DNA fuel or protease-powered walkers, this strategy enhances processivity and stability while reducing costs. This review is structured around \"structure-performance-application\": it first outlines the components of DNA walkers and the structural roles of AuNPs, then discusses performance optimization through 3D tracks and DNAzyme tuning, and finally summarizes applications in molecular imaging and biosensing. Future development trends of DNA walkers have been delved into, and their research prospects have been presented in this article, with a focus on theranostic integration and in vivo dynamic imaging, positioning DNA walkers as intelligent platforms for precision diagnostics and targeted therapy. STATEMENT OF SIGNIFICANCE: This review highlights the transformative potential of DNAzyme-driven DNA walkers, which leverage the autonomous catalytic activity of DNAzymes to achieve unparalleled operational efficiency, stability, cost-effectiveness, and programmability compared to conventional fuel strand- or protease-powered systems. Central to their advancement is the integration of gold nanoparticles (AuNPs), whose exceptional biocompatibility, large surface area, and versatile surface functionalization capabilities enable robust construction and enhanced performance of DNA walker platforms. By systematically outlining the synergy between DNAzyme walkers and AuNPs, this work underscores their groundbreaking applications in biosensing and molecular imaging, offering ultrasensitive detection and precise spatial resolution for biomedical research. Furthermore, the discussion on future trends positions DNA walkers as pivotal tools poised to drive innovation in nanotechnology, diagnostics, and targeted therapeutics, bridging fundamental science with real-world clinical and analytical challenges.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093305","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":"Formulation, in vitro physico-chemical and biological assessment of calcium pyrophosphate dihydrate cement for bone tissue engineering.","authors":"L Touati, C Leroy, C Damia, M Renard, O Marsan, M Durand, H K Ea, J Amédée, C Combes","doi":"10.1016/j.actbio.2025.09.022","DOIUrl":"10.1016/j.actbio.2025.09.022","url":null,"abstract":"<p><p>Calcium pyrophosphate dihydrate (CPPD: Ca₂P₂O₇·2H₂O) crystals are known for their inflammatory potential as pathological calcifications in osteoarthritis while several studies showed the promising potential of calcium pyrophosphate-based materials as bioactive bone substitutes. This study presents for the first time the feasibility to formulate a m-CPPDc cement consisting of pure agglomerated monoclinic CPPD (m-CPPD) crystals with a lower inflammatory potential than a biomimetic carbonated apatite cement (Apc): m-CPPDc-induced interleukin-1β production was 2 times lower than Apc and 2.5 times lower than isolated m-CPPD crystals. In addition, the possibility to reach a biphasic cement composition (m-CPPD associated with the monoclinic calcium pyrophosphate tetrahydrate (m-CPPT-β) metastable phase) was exemplified by varying a formulation parameter which could be of interest to modulate and controlled the material resorbability and inflammatory response. Through an original methodology combining ortho- and pyrophosphate ions titration, in vitro biological and acellular cement physico-chemical evolution tests, we can correlate the enhanced hydrolysis of pyrophosphate ions released from this cement to the action of ALP enzyme (about 3 times more orthophosphate ions at day 2 and 6 whereas no pyrophosphate was detected) and/or hMSC cells (about 37 % less pyroP at day 4). Interestingly m-CPPDc cement combines a high stability during its evolution in different aqueous media (SBF, TRIS buffer, TRIS buffer including ALP enzymes) at 37 °C while releasing higher calcium (3 times more) and orthophosphate ions concentration than a biomimetic apatite cement. Overall, these results illustrate that the cement formulation strategy implemented in this study opens perspectives to develop a new family of phosphocalcic cements fully composed of hydrated calcium pyrophosphate(s) and intrinsically biologically responsive in vitro. STATEMENT OF SIGNIFICANCE: We developed a formulation strategy demonstrating for the first time the feasibility to obtain a pure calcium pyrophosphate dihydrate (CPPD) cement but also the possibility to reach biphasic cement compositions by playing with hydrated calcium pyrophosphate phases. This material consisting of agglomerated CPPD crystals combines low inflammatory potential, cytocompatibility and a high stability in different aqueous media at 37 °C while releasing higher calcium and orthophosphate ions than a biomimetic apatite cement. Both in vitro cell test including an original pyrophosphate follow-up method and physico-chemical testing revealed a correlation between the hydrolysis of pyrophosphate released from cement to the action of enzymes and/or hMSC cells paving the way to a new family of biologically responsive phosphocalcic bone cements.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In situ fluid-to-solid converting injectable wet adhesive for comminuted fracture repair via water-activated bonding.","authors":"Shijie Shi, Huan Wang, Song Chen, Ran You, Moyan Li, Xuemei Tang, Jun Luo, Jianshu Li, Shaodong Hu, Jiaojiao Yang, Jiyao Li, Bin Li, Siying Tao","doi":"10.1016/j.actbio.2025.09.018","DOIUrl":"10.1016/j.actbio.2025.09.018","url":null,"abstract":"<p><p>Comminuted fractures, characterized by multiple irregular bone fragments, present significant challenges for traditional fixation methods like plates and screws, often resulting in complex surgeries and delayed healing. Injectable hydrogel adhesives have been applied for comminuted fractures, but face challenges such as excessive fluidity before curing and curing processes that involve high temperatures or ionic release, which can result in material leakage, localized inflammation and reduced adhesion. To address these challenges, we developed a humidity-responsive hydrogel adhesive system, comprised of tannic acid (TA), silk fibroin (SF), amorphous calcium phosphate (ACP), and guanidine hydrochloride (GuCl). GuCl acts as a hydrogen bond disruptor, which enables faster and more complete penetration of the hydrogels into bone fragments. Upon exposure to body fluids, GuCl diffuses out, allowing hydrogen bonds to reform. This process enabled the hydrogel to dynamically transition from a low-modulus, injectable state to a high-modulus, adhesive gel. Moreover, the presence of ACP enhanced the mechanical and mineralization properties of the hydrogel. The resultant hydrogel showed desirable biocompatibility and osteogenic properties, both in vitro and in vivo. Collectively, this research addressed the critical issue of the difficulty of injectable bone bonding materials to penetrate irregular bone fragments and maintain good biocompatibility while rapidly solidifying in situ. This system demonstrates significant potential for clinical application in the effectively treatment of complex bone injuries, especially for in situ repair of comminuted fractures. STATEMENT OF SIGNIFICANCE: Comminuted fractures involve multiple irregular bone fragments, posing serious challenges for fixation using traditional hardware. Existing injectable adhesives often suffer from poor cohesion, inflammatory side effects, and inadequate curing control. We present a moisture-responsive hydrogel adhesive (rTSA-G), composed of tannic acid, silk fibroin, amorphous calcium phosphate, and guanidine hydrochloride. This system exhibits high injectability, transitions rapidly to a solid upon contact with water, and provides strong adhesion, mechanical support, and osteoinductive properties. By addressing the key limitations of current bone adhesives, this strategy offers a promising alternative for minimally invasive treatment of complex fractures and advances the development of next-generation stimulus-responsive biomaterials.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093208","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":"Ultrasound-activated directional and controllable nitric oxide therapy for vascular calcification repair through the modulation of eNOS/iNOS homeostasis.","authors":"Chunxia Liu, Mengjing Lin, Jing Dai, Binglin Chen, Jiali Wang, Jingyi Li, Xiaoyun Li, Ziyun Jiang, Miao Xiao, Mingliang Tang","doi":"10.1016/j.actbio.2025.09.024","DOIUrl":"10.1016/j.actbio.2025.09.024","url":null,"abstract":"<p><p>Vascular calcification (VC) is a critical pathological hallmark of cardiovascular diseases but current therapeutic options remain inadequate. Nitric oxide (NO) homeostasis plays a vital role in endothelial function and phenotypic transformation of vascular smooth muscle cells (VSMCs), two key pathological processes in VC. In this study, Fe₃O₄@PDA@BNN6 (FPB) nanoparticles were prepared for directional and controllable NO therapy. Magnetic field enriched the nanoparticles to the site of VC and ultrasound triggered the controllable release of NO to regulate the homeostasis of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS), further activated sGC-cGMP-PKG signaling pathway. Both in the rat and in vitro VC models, the innovative therapy inhibited osteogenic like transformation of VSMCs, alleviated endothelial inflammatory response, regulated eNOS/iNOS homeostasis, and effectively improved VC. By ensuring optimal NO bioavailability for vascular homeostasis, this magneto-ultrasonically controlled strategy overcomes limitations of conventional NO-based therapies and paves the way for precision NO-mediated interventions in cardiovascular diseases. STATEMENT OF SIGNIFICANCE: Engineering innovation: Dual-modality nanoparticle system for precision NO delivery: Magnetic guidance directs the FPB to calcified lesions, reducing systemic off-target effects. Ultrasound-triggered release of NO to ensure on-demand delivery at VC sites. Mechanistic innovation: Restoring eNOS/iNOS homeostasis as a therapeutic axis: Directional and controllable NO therapy uniquely modulates eNOS/iNOS homeostasis, further activating the sGC-cGMP-PKG signaling pathway.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093357","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":"Dual-functional bioinspired nanospray for accelerated wound healing: Visible light-activated bismuth composites.","authors":"Yingwen Wang, Xuelei Xu, Yubing Jiao, Lili Shen, Ying Li, Min Mao, Wei Zhang, Jinguang Yang","doi":"10.1016/j.actbio.2025.09.019","DOIUrl":"10.1016/j.actbio.2025.09.019","url":null,"abstract":"<p><p>Infectious wound healing has garnered significant attention due to the increasing prevalence of drug-resistant bacteria, with photodynamic therapy (PDT) emerging as a promising non-invasive approach. Among PDT techniques, visible-light-activated therapies hold great potential. Nevertheless, current applications face critical challenges, such as non-specific targeting of bacteria, limited photodynamic efficacy, and insufficient oxygen supply. To resolve these limitations, the study introduces an innovative dual-functional bioinspired nanoparticle system. The aptamer-modified macrophage membranes enable high specificity and selectivity of the hybrid BiVO₄/BiOI toward S. aureus. Simultaneously, the heterojunction formed between BiVO₄ and BiOI quantum dots not only expands the photocatalytic active surface area but also significantly accelerates the separation of photogenerated charge carriers, thereby enhancing PDT activity. By utilizing visible-light irradiation to catalyze H₂O molecules, the system generates reactive oxygen species (ROS) independent of ambient oxygen levels, overcoming the limitation of oxygen content availability in traditional PDT approaches. Computational simulations further confirm that the generated ROS effectively disrupt bacterial phospholipid bilayers, enhancing bactericidal efficacy. A series of biological evaluations, including in vitro and in vivo antibacterial assays and cell migration studies, validate the dual-functional of the bioinspired nanoparticles in accelerating wound healing. Overall, this multifunctional bioinspired nanocomposite, with its targeted delivery, visible-light responsiveness, and potent antibacterial properties, demonstrates substantial promise for applications in treating infectious wounds. STATEMENT OF SIGNIFICANCE: Infectious wound healing has garnered significant attention due to the increasing prevalence of drug-resistant bacteria, with photodynamic therapy emerging as a promising non-invasive approach. The heterostructure formed between BiVO₄ and BiOI QDs exhibits highly efficient photocatalytic activity, which maximizes ROS production, leading to more effective bacterial eradication. To date, this specific heterostructure has not been extensively studied. Moreover, the aptamer-modified macrophage cell membranes achieve high specificity and selectivity of the hybrid BiVO₄/BiOI toward S. aureus. This multifunctional bioinspired nanocomposite, with its targeted delivery, visible-light responsiveness, and potent antibacterial properties, demonstrates substantial promise in medical field.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093189","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":"Copper-manganese bimetallic oxide-encapsulated hydrogels with multienzyme activities accelerate MRSA-infected wound healing by disrupting bacterial protein expression.","authors":"Hanzhu Shi, Wei Zhang, Ying Zang, Xueting Guo, Zhengwan Jiang, Yiwei Sun, Chenwei Dai, Hengguo Zhang, Xianwen Wang","doi":"10.1016/j.actbio.2025.09.017","DOIUrl":"10.1016/j.actbio.2025.09.017","url":null,"abstract":"<p><p>Wound therapy for pathogenic infections remains a medical challenge worldwide. Nanozyme-based catalytic therapy provides a new therapeutic strategy for combating drug-resistant bacterial infections. However, its limited catalytic activity, nonlethal death mechanism, and imperfect wound repair capacity restrict its further development. In this work, a temperature-sensitive Cu_1.5Mn_1.5O₄/F127 hydrogel was prepared by encapsulating Cu_1.5Mn_1.5O₄ nanospheres (Cu_1.5Mn_1.5O₄ NSs) with multienzyme activities and photothermal properties in F127. The obtained hydrogel possesses oxidase-like (OXD-like), peroxidase-like (POD-like) and glutathione peroxidase-like (GSH-Px-like) activities, achieving efficient sterilization through the synergistic effects of reactive oxygen species (ROS), photothermal effects and glutathione depletion ability. Moreover, the hydrogel can slowly release copper and manganese ions at the wound site, accelerating wound healing by promoting collagen deposition and angiogenesis. Further prokaryotic RNA sequencing (RNA-seq) analysis revealed that the efficient bactericidal ability of the Cu_1.5Mn_1.5O₄/F127 hydrogel is due mainly to its ability to disrupt bacterial cell wall functions and affect protein expression and nucleotide metabolic pathways. In vivo experiments confirmed that the hydrogel can effectively prevent bleeding, sterilize and promote wound healing. Thus, this work highlights the great potential of the Cu_1.5Mn_1.5O₄/F127 hydrogel as a wound dressing for the treatment of bacterial infections and provides new research ideas for the application of nanozyme-based hydrogels in the medical field. STATEMENT OF SIGNIFICANCE: 1) Cu_1.5Mn_1.5O₄/F127 composite hydrogel exhibits enhanced multi-enzyme activity, ROS generation and GSH consumption, which improves the antibacterial therapeutic effect of traditional nanozymes. 2) Cu_1.5Mn_1.5O₄/F127 hydrogel has prominent photothermal properties and provides a multimodal synergistic antibacterial treatment platform. 3) Cu_1.5Mn_1.5O₄/F127 hydrogel can affect the core physiological activities of bacteria by blocking nucleotide metabolism and inhibiting protein expression, thereby achieving efficient sterilization. 4) The temperature sensitivity and hemostatic effect of Cu_1.5Mn_1.5O₄/F127 hydrogel enable it to promote wound healing while being effectively antibacterial. 5) Cu_1.5Mn_1.5O₄/F127 hydrogel can release Cu and Mn ions slowly in a weakly acidic environment on the wound surface, accelerating collagen deposition and angiogenesis and thereby promoting tissue repair.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093276","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":"Lipid nanoparticles hijack neutrophils for enhanced anti-inflammatory and stroke therapy.","authors":"Qian Cheng, Yufei Zhang, Guomin Su, Yuhao Xue, Xinyu Zou, Madiha Zahra Syeda, Ruwei Jie, Jinlong Wan, Yang Li, Qiuchen Bi, Heping Zhu, He Bai, Sanjeev Nirala, Qing Lan, Longguang Tang, Qingchun Mu","doi":"10.1016/j.actbio.2025.09.015","DOIUrl":"10.1016/j.actbio.2025.09.015","url":null,"abstract":"<p><p>Ischemic stroke remains a critical global health challenge with limited therapeutic options targeting secondary neuroinflammation. Emerging evidence implicates neutrophil extracellular traps (NETs) as key mediators of blood-brain barrier (BBB) disruption and neuronal damage during ischemia-reperfusion injury. Capitalizing on this pathophysiology, we engineered a neutrophil-homing lipid nanoparticle (LNP) platform encapsulating brensocatib (AZD7986), an FDA-designated breakthrough therapy that inhibits dipeptidyl peptidase 1 (DPP1) to block activation of neutrophil serine proteases. The LNPs exploit intrinsic neutrophil chemotaxis to achieve BBB penetration and lesion-specific accumulation, enabling localized release of AZD7986 in ischemic brain tissue. In a murine middle cerebral artery occlusion (MCAO) model, targeted LNP delivery (T-AZD) significantly prolonged survival, reduced cerebral infarct volume by 45 %, and suppressed NET formation through inhibition of elastase and cathepsin G activity (p < 0.01 vs. non-targeted controls). Mechanistically, T-AZD attenuated reactive astrogliosis and decreased pro-inflammatory cytokine levels (IL-6, TNF-α) by >50 %, demonstrating dual anti-inflammatory and neuroprotective effects. This neutrophil-directed nanoplatform addresses critical limitations of systemic DPP1 inhibition through spatiotemporal control of drug release, while exhibiting enhanced biocompatibility in hematological and histological safety assessments. By integrating targeted neutrophil trafficking with precision protease inhibition, our strategy establishes a translatable paradigm for modulating neuroimmune responses in cerebrovascular diseases. STATEMENT OF SIGNIFICANCE: Ischemic stroke lacks effective therapies targeting neuroinflammation. We developed neutrophil-homing lipid nanoparticles (LNPs) delivering brensocatib (AZD7986), a DPP1 inhibitor, to suppress neutrophil extracellular traps (NETs) and neuroinflammation. In a murine stroke model, targeted LNPs reduced infarct volume by 45 %, inhibited NET formation, and lowered pro-inflammatory cytokines (>50 %), demonstrating neuroprotection and anti-inflammatory effects. This approach enables precise drug delivery to ischemic brain tissue, overcoming limitations of systemic therapy while maintaining safety. By combining neutrophil-directed targeting with protease inhibition, our strategy offers a translatable platform for modulating neuroimmune responses in cerebrovascular diseases.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066775","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":"Electrosprayed hydrogel microsphere dressing promotes vascularization and accelerates wound healing.","authors":"Qilong Wang, Zeyu Xu, Xuedi Weng, Min Ni, Michael Adu-Frimpong, Xiaoli Li, Yize Lv, Jinghan Li, Hongran Huang, Yue Sun, Ziyun Wu, Xia Cao","doi":"10.1016/j.actbio.2025.09.016","DOIUrl":"10.1016/j.actbio.2025.09.016","url":null,"abstract":"<p><p>Repair of skin injuries is often hindered by the challenge of neovascularization, particularly in severely damaged wounds that struggle to self-heal, potentially leading to organ dysfunction or even death. Thus, promoting vascularization is crucial for effective skin repair. This study employed electrostatic spraying to fabricate methacrylated hyaluronic acid (HAMA) hydrogel microspheres for encapsulation of ectodermal mesenchymal stem cells (EMSCs), and optimization of the process parameters to assess their biocompatibility. Under in vitro conditions, EMSCs microspheres were successfully induced to differentiate into structures with vascular networks. Additionally, the optimal modification ratio of dopamine-modified hyaluronic acid (HADA) was determined to enhance the adhesive and mechanical properties of the dressing. Based on these findings, a dressing incorporating cell microspheres and adhesive hydrogels was developed. This dressing demonstrated formation of microvascular structures in vitro. Upon in vivo transplantation, it integrated tightly with surrounding tissues, modulated the inflammatory response, and accelerated wound healing in mouse model. This composite dressing, integrating cell-laden microspheres within a hydrogel's framework, offers a simple and effective approach to promote skin microvascular. STATEMENT OF SIGNIFICANCE: This study describes a hydrogel dressing that uses electrostatically sprayed methacrylated hyaluronic acid (HAMA) microspheres to encapsulate ectodermal mesenchymal stem cells (EMSCs). The hydrogel composition was optimized using dopamine-modified hyaluronic acid (HADA), which improved adhesion, while methacrylated polyvinyl alcohol (PVAMA) enhanced mechanical strength. This highly effective, low-risk hydrogel dressing promoted angiogenesis and accelerated wound healing. The results of this study highlight the potential of hydrogel dressing for clinical applications in tissue engineering and regenerative medicine, thus providing a promising strategy for the treatment of severe skin injuries.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066780","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":"Nanoparticles coated with immune cell hybrid membranes for targeted delivery of janus kinase inhibitors and synergistic treatment of autoimmune myocarditis.","authors":"Zhenhao Zhang, Yulong Xiong, Shangyu Liu, Lishui Shen, Lihui Zheng, Ligang Ding, Lingmin Wu, Limin Liu, Minghao Zhao, Le Li, Zhuxin Zhang, Sheng Su, Xi Peng, Likun Zhou, Mengtong Xu, Yan Yao","doi":"10.1016/j.actbio.2025.09.013","DOIUrl":"10.1016/j.actbio.2025.09.013","url":null,"abstract":"<p><p>Autoimmune myocarditis is a complicated, inflammatory heart disease with high morbidity and mortality. Interferon (IFN)-γ-mediated classical activated macrophage (M1 macrophage) polarization and pyroptosis play a vital role in immune injury in myocarditis. Baricitinib, a selective Janus kinase (JAK) 1 and JAK2 inhibitor, has been used in the treatment of some systemic autoimmune diseases to effectively suppress pro-inflammatory macrophages by blocking the JAK2-signal transducer and activator of transcription 1 (STAT1) signaling pathway. Nevertheless, its application to autoimmune myocarditis was hindered due to the difficulty of delivering and accumulating the drug in heart tissue. To overcome these limitations, we synthesized a hybrid membrane containing CC motif chemokine receptor (CCR) 1 and CXC motif chemokine receptor (CXCR) 3 from activated RAW264.7 and EL4 cell lines to target inflammatory lesions. Furthermore, mesoporous polydopamine (MPDA) was employed due to its synergistic effects, including high drug loading efficiency, reactive oxygen species (ROS) adsorption, and dual responsiveness to glutathione (GSH) and pH, to fabricate RAW-EL4 hybrid membrane-coated Baricitinib-MPDA nanoparticles (BM@[RAW-EL4] NPs) for Baricitinib delivery. Subsequent in vitro and in vivo experiments verified that BM@[RAW-EL4] NPs significantly inhibited inflammatory infiltration and heart tissue injury by precisely suppressing macrophage polarization and pyroptosis. Biotoxicity and biosafety tests also revealed the biocompatibility of BM@[RAW-EL4] NPs, which provided the foundation for further clinical translation. Hence, the biomimetic BM@[RAW-EL4] NPs offer new heart-specific delivery opportunities, representing a versatile platform for targeted therapy in autoimmune myocarditis. STATEMENT OF SIGNIFICANCE: Autoimmune myocarditis is defined as an intense immune injury in the heart tissue, with current treatment far from satisfactory. IFN-γ-mediated M1 macrophage polarization and pyroptosis are crucial to disease progression. In this study, we created RAW-EL4 hybrid membrane-coated Baricitinib-MPDA nanoparticles (BM@[RAW-EL4] NPs) to achieve targeted delivery of an IFN-γ inhibitor to the inflammatory site. RAW-EL4 hybrid membranes endowed the nanomedicine with chemotactic property under the mechanism of activated CCR1-CCL7/8 and CXCR3-CXCL9/10 axis. MPDA exhibited a high drug-loading efficiency of 49.0 % and dual responsiveness to GSH and pH. We also observed its ability to clear ROS in the study. These characteristics of MPDA promoted the release of Baricitinib and macrophage suppression. In vivo experiments revealed the therapeutic effect and biosafety of BM@[RAW-EL4] NPs for the potential application to autoimmune myocarditis.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058807","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}