Acta Biomaterialia最新文献

{"title":"A sulfonated cartilage interpenetrating polymer network reinforces and protects the extracellular matrix of degraded cartilage","authors":"Christian D. DeMoya ,&nbsp;Pierson Husted ,&nbsp;Dev R. Mehrotra ,&nbsp;Michael B. Albro ,&nbsp;Brian D. Snyder ,&nbsp;Mark W. Grinstaff","doi":"10.1016/j.actbio.2025.12.028","DOIUrl":"10.1016/j.actbio.2025.12.028","url":null,"abstract":"<div><div>Cartilage extracellular matrix (ECM) comprises a type-II collagen fibril network that affords structure and tensile strength, complemented by a negatively charged, sulfated glycosaminoglycan (GAG) matrix that retains interstitial water. These components act synergistically, bestowing the rheological and tribological material properties essential to cartilage function. At the onset of osteoarthritis, a disease characterized by cartilage degeneration, GAGs diminish from the ECM reducing interstitial fluid load support (IFLS), equilibrium stiffness, and transferring load to the collagen fibril network, which subsequently breaks down, culminating in increased hydraulic permeability, and decreased cartilage stiffness. We restore the material properties of damaged cartilage critical to diarthrodial joint function by forming an interpenetrating polymer network (IPN) with the native collagen using a synthetic, hydrophilic, and biocompatible GAG-mimetic polymer. Upon visible light activation, the monomer, 3-sulfopropylmethacrylate (SPM), and the crosslinker, polyethylene glycol diacrylate (PEGDA), form a sulfonated and anionic IPN that fills the existing porous collagen matrix of degraded cartilage. Mechanistically, the highly sulfonated, anionic SPM IPN retards water transport, reestablishes collagen fibril network integrity, and restores tissue equilibrium stiffness, thereby returning the stiffness and viscoelastic properties of degraded cartilage to levels near healthy cartilage. Additionally, the SPM IPN protects cartilage by reducing the infiltration of inflammatory cytokines that are known to upregulate catabolic matrix metalloproteinases and downregulate GAG production.</div></div><div><h3>Statement of significance</h3><div>Amelioration of OA requires a comprehensive approach: neutralize or impede catabolic enzymes that degrade cartilage and reconstitute damaged cartilage by augmenting tissue ECM constituents. Currently, there are no clinical treatments that restore the viscoelastic material properties of hyaline cartilage tissue critical to its mechanical function and impart chondroprotection after OA induction. This work suggests that reconstituting GAG-depleted cartilage using a synthetic sulfonated interpenetrating polymer to reestablish IFLS instilled into the joint and polymerized with white light during conventional arthroscopy represents an effective, and minimally invasive strategy to restore the material properties of cartilage in the early stages of OA.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 202-215"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual Inhibition of KRAS G12D and PI3K/BRD4 signaling overcomes therapeutic resistance in pancreatic cancer","authors":"Yashwardhan Ghanwatkar,&nbsp;Sohan Mahto,&nbsp;Ajaykumar Chittipolu,&nbsp;Raghu Ramanathan,&nbsp;Prakash Shrestha,&nbsp;Ram I. Mahato","doi":"10.1016/j.actbio.2025.12.049","DOIUrl":"10.1016/j.actbio.2025.12.049","url":null,"abstract":"<div><div>Oncogenic KRAS G12D mutations drive pancreatic ductal adenocarcinoma (PDAC) but face therapeutic resistance from pathway reactivation. We synthesized MDP5, a dual BRD4/PI3K inhibitor, to address this issue. When combined with the KRAS G12D inhibitor MRTX1133, MDP5 resensitized resistant cancer cells. This combination synergistically enhanced apoptosis and proliferation inhibition, outperforming the standard-of-care, Gemcitabine (GEM). This dual-inhibition strategy effectively counters resistance mechanisms in KRAS-mutant PDAC, offering a promising therapeutic approach. We formulated MUC4-targeted polymeric nanoparticles co-loading MRTX1133 (8.3%) and MDP5 (7.4%) that exhibited pH-responsive release and uniform morphology. This targeted delivery translated to superior anti-tumor efficacy, as the combination of NPs markedly reduced tumor burden more effectively than single-drug treatments or a polymer-Gemcitabine conjugate. Importantly, this potent therapeutic effect was achieved without inducing detectable liver highlighting the potential, safe, and effective cancer therapy. Mechanistically, dual targeting reduced p-AKT and YAP1, depleted CD44⁺/ALDH⁺ cancer-stem-like cells, and reprogrammed the tumor immune microenvironment by elevating CD8a and CD86 while lowering Ly-6 G. Targeted co-delivery of MRTX1133 and MDP5 simultaneously inhibits the KRAS G12D and PI3K pathways. This dual-action approach aims to overcome therapeutic resistance, offering potentially more durable and precise treatment for patients with KRAS G12D-mutant pancreatic cancer.</div></div><div><h3>Statement of significance</h3><div>Pancreatic ductal adenocarcinoma (PDAC) is commonly driven by KRAS G12D, yet the KRAS G12D inhibitor MRTX1133 faces rapid adaptive resistance and delivery hurdles. We engineered MUC4-targeted polymer nanoparticles that co-deliver MRTX1133 with MDP5, a dual BRD4/PI3K blocker. The particles show uniform size, high loading, and pH-triggered release, increasing intratumoral drug levels versus free drugs. In orthotopic PDAC, the combination outperformed monotherapies and gemcitabine without overt toxicity. Mechanistically, dual inhibition suppresses AKT/YAP signaling, depletes CD44⁺/ALDH⁺ cells, and shifts the tumor immune milieu (↑CD8a, ↑CD86, ↓Ly-6 G). By integrating molecular targeting with multi-pathway blockade, this work addresses two major barriers—resistance and delivery—and outlines a generalizable strategy to improve precision nano therapy for KRAS-mutant pancreatic cancer.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 637-654"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145851663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tunable wrinkled topographies direct dendritic cell maturation and immune phenotypes","authors":"Ajay Chavda ,&nbsp;Xingwu Zhou ,&nbsp;Mohammad Asadi Tokmedash ,&nbsp;James J. Moon ,&nbsp;Jouha Min","doi":"10.1016/j.actbio.2025.12.050","DOIUrl":"10.1016/j.actbio.2025.12.050","url":null,"abstract":"<div><div>Dendritic cells (DCs) are potent regulators of immunity with therapeutic potential in cancer, autoimmune disorders, and implant tolerance. However, clinical translation is limited by poor scalability, limited survival/retention after delivery, and difficulty controlling DC immune responses. Biomaterials have been explored to address these challenges, but the role of surface topography in DC regulation remains poorly understood. Here, we used a custom bottom-up nanofabrication method to create wrinkled multilayer coatings with precisely tunable nano-, submicro-, and microscale topographies. Using this platform, we systematically investigated the impact of topographical cues on DC behavior, using the DC2.4 cell line and primary bone marrow-derived DCs (BMDCs) as biological models. We found that distinct topographies drive DCs toward divergent phenotypes. Microscale wrinkles promoted an immunogenic mature state, with elevated pro-inflammatory cytokines (IL-6, IL-12, and TNF-α), high co-stimulation and NF-κB activation, and strong T-cell activation potential. Submicro-scale patterns induced an intermediate mature state with homeostatic and tolerogenic potential. Submicro exhibited increased TGF-β and IL-10, reduced cross-presentation, and weak T-cell activation in the DC2.4 cell line. However, BMDCs expressed intermediate maturation marker levels and NF-κB activation without increased cytokine secretion. In contrast, nanoscale wrinkles and planar controls preserved DC immaturity with high antigen uptake and low maturation, though planar surfaces showed poor adhesion, limiting their utility for delivery or <em>ex vivo</em> culture. These findings identify surface topography as a key regulator of DC immune programming. Our versatile, scalable fabrication strategy provides a broadly applicable platform for probing immune cell–material interactions and advancing biomaterials for DC-based immunotherapies and related applications.</div></div><div><h3>Statement of significance</h3><div>Immune therapies increasingly rely on dendritic cells (DCs), yet current biomaterials mainly use biochemical signals to guide their behavior. This study introduces a new approach using precisely engineered surface topographies to influence DC function through physical cues alone. By creating tunable wrinkled MXene coatings, we show for the first time that different topographical scales can maintain DC immaturity or induce maturation with either homeostatic or immunogenic polarization potential. Unlike prior studies that focus on general surface roughness or chemistry, we demonstrate a topography-specific effect validated in both cell line and primary DCs. This work establishes surface architecture as a powerful design parameter for immune-instructive biomaterials, with potential to improve vaccine development and cell-based immunotherapies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 428-443"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical characterization of infarcted porcine hearts using left anterior descending and left circumflex coronary artery models","authors":"Nicolás Laita ,&nbsp;Alejandro Aparici-Gil ,&nbsp;Aida Oliván-Viguera ,&nbsp;Alba Pérez-Martínez ,&nbsp;Ming Wu ,&nbsp;Manuel García de Yébenes ,&nbsp;Gloria Abizanda ,&nbsp;Stephan Janssens ,&nbsp;Felipe Prósper ,&nbsp;Manuel M. Mazo Vega ,&nbsp;Miguel Ángel Martínez ,&nbsp;Manuel Doblaré ,&nbsp;Estefanía Peña","doi":"10.1016/j.actbio.2025.12.051","DOIUrl":"10.1016/j.actbio.2025.12.051","url":null,"abstract":"<div><div>This study comprehensively analyzes passive mechanical and structural changes of cardiac tissue 6 weeks after myocardial infarction (MI) by biaxial, simple triaxial shear, and confined compression characterization. We considered a porcine model, comparing two MI types: Left Anterior Descending (LAD) artery and Left Circumflex (LCX) artery occlusions. LAD model generated apical transmurally infarcted hearts, while the LCX model generated medial heterogeneous infarctions ranging from mild locally infarcted tissue to transmurally infarcted tissue. Infarcted tissue exhibited significantly higher stiffness than healthy tissue. When peak equibiaxial stretch increases up to 20%, the stress increase is 2.19 for medial locally infarcted tissue, 4.49 for medial fully infarcted tissue, and 6.26 for apical fully infarcted tissue. Fully infarcted animals showed significant macroscopic geometrical remodeling, with thickness reductions in the infarcted area of 45%–60%, while locally infarcted tissue showed no thinning. The anisotropy of healthy myocardium was also altered post-MI: medial infarcts exhibited preferentially circumferential anisotropy, while apical infarctions increased isotropy. Histological analysis validated these mechanical alterations, revealing a substantial increase in collagen content in infarcted regions. In LCX infarctions, collagen distribution was uniformly aligned, whereas in LAD ones, its distribution was spatially heterogeneous. Non-infarcted tissue far from the infarction did not exhibit changes in mechanical properties or collagen content, suggesting a localized effect at least 6 weeks post-MI. These findings highlight the importance of considering the extent and location of MI when developing personalized therapeutic strategies.</div><div><em>Statement of Significance</em></div><div>This work provides a comprehensive mechanical and histological assessment of post-infarct porcine myocardium using advanced multimodal testing. Unlike previous studies, we compare two infarct types (LAD and LCX) under identical conditions and examine regional and severity-dependent differences in stiffness, compressibility, and anisotropy. We show that infarction induces local rather than global changes in tissue passive mechanics, modulated by infarct geometry and scar distribution. These insights support more accurate cardiac modeling and may guide personalized therapeutic strategies after myocardial infarction.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 459-480"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix-modulating pH-gated hydrogel for coordinated regulation of cancer-associated fibroblast phenotype and Mn²⁺-STING activation for enhanced tumor immunotherapy","authors":"Tinghua Li,&nbsp;Yazhen Wang,&nbsp;Jiahui Zhu,&nbsp;Xiaoxian Zhang,&nbsp;Xuequan Zhang,&nbsp;Lei Lei,&nbsp;Lianyi Yang,&nbsp;Peng Wang,&nbsp;Qiusheng Wang,&nbsp;Ziyun He,&nbsp;Bin He,&nbsp;Jun Cao","doi":"10.1016/j.actbio.2026.01.014","DOIUrl":"10.1016/j.actbio.2026.01.014","url":null,"abstract":"<div><div>The tumor microenvironment (TME), particularly its cancer-associated fibroblast (CAF)-driven fibrotic stroma and immunosuppressive components, forms intertwined physical and immune barriers that impede the efficacy of immunotherapy. To address this challenge, we developed a pH-gated hydrogel platform to modulate CAF-resulted TME barriers and activate potent antitumor immunity. This dynamic network, constructed by Schiff base crosslinking between carboxymethyl chitosan and aldehyde-functionalized hyaluronic acid, was utilized for the co-delivery of pirfenidone (PFD) and manganese-curcumin nanoparticles (MC). In the acidic TME, PFD was released rapidly from hydrogel to modulate CAF phenotype, thereby attenuating the formation of fibrotic stroma. The internalized MC orchestrated three synergistic therapeutic functions: (1) suppressing VEGF-mediated angiogenesis <em>via</em> curcumin, (2) generating reactive oxygen species through Mn²⁺-catalyzed Fenton-like reactions, and (3) promoting dendritic cell maturation by activating the cGAS-STING pathway with Mn²⁺. Upon 808 nm NIR laser irradiation, MC exhibited potent photothermal conversion efficacy, inducing localized hyperthermia that further amplified ROS production, and triggered immunogenic cell death. This coordinated cascade thereby elicited robust antitumor immunity, as evidenced by the upregulated expression of proinflammatory cytokines (TNF-α, IFN-γ, IL-6) and enhanced CD8⁺ T cell infiltration. Notably, this strategy achieved marked tumor regression in B16F10 melanoma-bearing mice. Thus, this work established a TME-responsive platform that coordinated barrier modulation with multimodal therapeutic synergy, providing a promising paradigm for solid tumor immunotherapy.</div></div><div><h3>Statement of significance</h3><div>Modulating the tumor microenvironment (TME) by targeting cancer-associated fibroblasts (CAFs) represent a promising strategy to enhance the efficacy of immunotherapy. Here, we develop a pH-gated hydrogel platform that enables the controlled delivery of pirfenidone and manganese-curcumin nanoparticles (MC), thereby facilitating the regulation of CAF-mediated fibrotic barriers followed by the activation of antitumor immunity. The released MC integrate antiangiogenic activity, ROS amplification, STING pathway activation, and photothermal ablation into a unified therapeutic system. Moreover, the photothermal effect further amplifies ROS generation and STING signaling, resulting in remodeling of the TME. This coordinated cascade elicits robust T-cell activation and cytokine secretion, achieving marked tumor eradication in murine melanoma models. Overall, this study establishes a therapeutic paradigm that integrates stromal barrier modulation with immune activation to achieve more effective tumor treatment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 655-670"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current progress of bio-fabrication in breast reconstruction","authors":"Xuanwei Zhang,&nbsp;Zhuohang Du,&nbsp;Zhenxing Wang,&nbsp;Chao Luo,&nbsp;Jiaming Sun","doi":"10.1016/j.actbio.2026.01.015","DOIUrl":"10.1016/j.actbio.2026.01.015","url":null,"abstract":"<div><div>Breast reconstruction is essential for restoring self-image and quality of life after mastectomy. While current methods using implants or autologous tissue are prevalent, they face challenges such as capsular contracture and volume loss. This review explores how bio-fabrication strategies are generating innovative scaffolds to overcome these limitations. We discuss the clinical use of bio-fabrication and detail preclinical progress in key areas: enhancing the biocompatibility and safety of implants, achieving soft tissue regeneration and vascularization, integrating antitumor therapy with reconstruction, and optimizing aesthetic outcomes. Finally, we outline future research directions for developing superior biomaterials to advance breast reconstruction.</div></div><div><h3>Statement of significance</h3><div>Current breast reconstruction methods are limited by complications, such as capsular contracture, volume loss, and infection. This review underscores the promise of bioengineered scaffolds, where biomaterials combined with bioactive agents and advanced fabrication (e.g., 3D printing) can recreate the natural breast microenvironment to support regeneration. This replication is crucial for promoting vascularization, adipogenesis, and tissue integration. Furthermore, we explore new strategies for modifying implant surfaces to minimize fibrosis and infection risks. This work serves as a guide for developing next-generation regenerative scaffolds and highlights their potential to significantly improve clinical outcomes in breast reconstruction by providing personalized, biocompatible, and functionally' as none of the work so far in the literature can truly replicate the natural breast microenvironment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 145-167"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-assembled charge-complementary hydrogel with sustained release of antimicrobial peptides for periodontitis treatment","authors":"Wener Chen ,&nbsp;Chaoning Zhan ,&nbsp;Chengfei Zhang ,&nbsp;Conrado Aparicio ,&nbsp;Simin Peng ,&nbsp;Zhou Ye ,&nbsp;Yifan Lin","doi":"10.1016/j.actbio.2026.01.025","DOIUrl":"10.1016/j.actbio.2026.01.025","url":null,"abstract":"<div><div>Periodontitis is a pathogenic microbial-infected disease where immune dysregulation promotes chronic inflammation and excessive osteoclast activity, causing progressive tissue destruction. Current therapeutic approaches face challenges in achieving sustained drug release in periodontal pockets. In this study, we construct a self-assembled peptide hydrogel by combining negatively charged peptide amphiphile (PA) with positively charged antimicrobial peptide GL13K, namely PA/GL13K. GL13K electrostatically binds to self-assembled PA nanofibers, promoting PA self-assembly that yields a denser hydrogel network. This structural reinforcement enables sustained GL13K release. The PA/GL13K hydrogel demonstrates potent antibacterial effects and immunomodulatory properties, suppressing pro-inflammatory M1 macrophage polarization while promoting anti-inflammatory M2 macrophage activation. Moreover, the PA/GL13K hydrogel inhibits osteoclast differentiation <em>in vitro</em>. In an experimental periodontitis mouse model, local periodontal injection of the PA/GL13K hydrogel reduced inflammatory infiltration and osteoclast-mediated bone resorption, effectively mitigating periodontal tissue destruction. These findings suggest that the self-assembled peptide hydrogel system may represent a potential multifunctional therapeutic approach for periodontal treatment.</div></div><div><h3>Statement of significance</h3><div>This study presents a peptide-based hydrogel system designed for the comprehensive treatment of periodontitis, addressing critical challenges in current therapeutic strategies. The self-assembled charge-complementary hydrogel is composed of negatively charged peptide amphiphile (PA) and positively charged antimicrobial peptide GL13K. GL13K electrostatically binds to self-assembled PA nanofibers, promoting PA self-assembly that yields a denser hydrogel network. This structural reinforcement enables sustained GL13K release. The system demonstrates synergistic effects, including antibacterial activity, immunomodulatory effects, and inhibition of osteoclastogenesis. Our findings highlight the hydrogel’s potential as a promising platform for periodontitis management, combining structural optimization with multifunctional therapeutic outcomes.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 251-265"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"M2 macrophage-derived exosome nanoplatform for targeted H2S delivery to alleviate hepatic ischemia–reperfusion injury via synergistic anti-oxidative, anti-inflammatory, and anti-ferroptotic effects","authors":"Tianci Zuo ,&nbsp;Chengge Shi ,&nbsp;Jiayu Li ,&nbsp;Diwei Li ,&nbsp;Xiaoming Luo ,&nbsp;Mengzhu Xu ,&nbsp;Mingli Su ,&nbsp;Hongyang Lu ,&nbsp;Yanmei Zhang ,&nbsp;Xiaowen Hu ,&nbsp;Qiang Zhou ,&nbsp;Quazi T.H. Shubhra ,&nbsp;Xiaosong He ,&nbsp;Xiaojun Cai","doi":"10.1016/j.actbio.2025.12.041","DOIUrl":"10.1016/j.actbio.2025.12.041","url":null,"abstract":"<div><div>Hepatic ischemia-reperfusion injury (HIRI) presents a critical challenge in liver surgery, transplantation, and trauma, driven by the interplay of oxidative stress, inflammation, and ferroptosis. Current treatments are limited by poor targeting and insufficient efficacy. Here, we develop a liver-targeted exosomal nanoplatform (DATS@M2-Exos) by encapsulating the H₂S donor diallyl trisulfide (DATS) into M2 macrophage-derived exosomes (M2-Exos), enabling liver-specific H₂S delivery. <em>In vitro</em>, DATS@M2-Exos exhibit good biocompatibility, efficient cellular uptake, and effective H₂S release, resulting in significant suppression of oxidative stress, inflammation, and ferroptosis by restoring GSH levels, enhancing GPX4 expression, and reducing Fe²⁺ and MDA accumulation. In a murine HIRI model, DATS@M2-Exos demonstrate strong hepatic tropism, significantly decrease serum ALT/AST levels, alleviate histopathological injury, while exhibiting favorable safety. RNA sequencing reveals potent antioxidant and anti-ferroptosis effects of DATS@M2-Exos via redox and lipid metabolic reprogramming, including activation of the GSH metabolic pathway, suppression of iron overload, and enhancement of GPX4 expression. Furthermore, DATS@M2-Exos exert dual immunomodulatory effects by suppressing the TNF-α/IL-1β/MAPK13 axis and promoting M2 macrophage polarization through activation of the PPAR pathway. This study presents an exosome-based nanotherapeutic for the targeted delivery of H₂S to coordinately combat oxidative stress, inflammation, and ferroptosis, offering a precise and effective strategy for HIRI treatment.</div></div><div><h3>Statement of significance</h3><div>Hepatic ischemia-reperfusion injury (HIRI) remains a critical challenge in liver surgery and transplantation, driven by oxidative stress, inflammation, and ferroptosis. Current therapies lack targeted delivery and multimodal efficacy. This study develops a liver-targeted exosomal nanoplatform (DATS@M2-Exos) by encapsulating the H₂S donor diallyl trisulfide (DATS) into M2 macrophage-derived exosomes (M2-Exos). DATS@M2-Exos demonstrate exceptional hepatic tropism, biocompatibility, and controlled H₂S release, synergistically combating oxidative stress (via GSH/GPX4 axis activation), inflammation (via PPAR-mediated M2 polarization), and ferroptosis (via iron overload suppression). <em>In vivo</em>, DATS@M2-Exos significantly reduce liver damage with no systemic toxicity. This work pioneers an exosome-based gas therapy platform, offering a precise, multifunctional strategy for HIRI and broader oxidative stress-related diseases.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 593-612"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “A dissolvable microneedle platform for the delivery of tumor-derived total RNA nanovaccines for enhanced tumor immunotherapy” [Acta Biomaterialia 2025, 199, 120-131]","authors":"Jiachen Wang ,&nbsp;Sicong Huang ,&nbsp;Huiye Wei ,&nbsp;Simin Liang ,&nbsp;Yuan Ding ,&nbsp;Zecong Xiao ,&nbsp;Xintao Shuai","doi":"10.1016/j.actbio.2025.12.036","DOIUrl":"10.1016/j.actbio.2025.12.036","url":null,"abstract":"","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 866-867"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphogenesis of the diamond-type stereom microlattice and the origin of saddle-shaped minimal surfaces in the echinoderm skeleton","authors":"Kamil Humański ,&nbsp;Giulio Facchini ,&nbsp;Jenifer Croce ,&nbsp;Dorota Kołbuk ,&nbsp;Philippe Dubois ,&nbsp;Przemysław Gorzelak","doi":"10.1016/j.actbio.2026.01.016","DOIUrl":"10.1016/j.actbio.2026.01.016","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Echinoderm endoskeleton has a unique trabecular microstructure, called stereom, which can exhibit highly ordered geometries. A striking example of these geometries is the recently discovered “diamond-type” stereom, characterized by a diamond triply periodic minimal surface (D-TPMS) and distinguished by exceptional mechanical and structural properties. Despite its promise for engineering applications, the morphogenesis of this microarchitecture remains poorly understood. Here, we applied a multimodal imaging and labeling approach to investigate the developmental processes underlying the formation of the diamond-type stereom in adults of a starfish &lt;em&gt;Protoreaster nodosus&lt;/em&gt;. We showed that this stereom type develops through two principal marginal growth patterns: trabecular trifurcation, which typically occurs horizontally on flat external plate surfaces, oriented approximately along the crystallographic {111} planes of the &lt;span&gt;d&lt;/span&gt;-TPMS; and trabecular bifurcation, which generally occurs along plate edges and between trifurcating zones, aligned with the crystallographic {100} planes of the &lt;span&gt;d&lt;/span&gt;-TPMS. Although these growth patterns may proceed at different rates, they are tightly coordinated, producing the coherent D-TPMS microarchitecture. Furthermore, we demonstrated that F-actin cytoskeletal deposition is consistently associated with active biomineralization fronts in both diamond-type and less ordered, galleried stereom. Notably, the formation of lateral bridges between adjacent stereom trabeculae is often preceded by catenoid-like F-actin structures, suggesting a guiding and templating role for the cytoskeleton in building trabecular connectivity and shaping its curvature. Given the recurrence of saddle-like features across stereom types, we hypothesize that minimal-surface geometries may emerge from tension-driven cytoskeletal dynamics acting as physical templates during biomineralization. Our observations underscore the critical involvement of the cytoskeleton in adult echinoderm biomineralization.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;Triple periodic minimal surfaces (TPMS) are geometrically regular, three-dimensionally repeating surfaces that minimize area by maintaining zero mean curvature. Among them, the diamond-type (D-TPMS) is notable for exceptional mechanical stability, uniform porosity, and low surface area-to-volume ratio. Although TPMS-like microarchitectures occur in nature, D-TPMS structures, with large lattice parameters (&gt;10 µm) are exceedingly rare; one natural example is the stereom of certain echinoderms. Yet the mechanism governing the formation of such ordered microstructures remains unresolved. We applied a multi-modal approach to investigate principles of diamond-type stereom morphogenesis. Our results provide key insight into the growth dynamics of this microarchitecture and highlight the essential role of the cytoskeleton, particularly F-actin, in guiding trabecular c","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"212 ","pages":"Pages 516-526"},"PeriodicalIF":9.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}