Acta Biomaterialia最新文献

{"title":"Ecomorphology and ontogeny modulate the mechanical properties of shark skin","authors":"Madeleine E. Hagood ,&nbsp;Joseph R.S. Alexander ,&nbsp;Michelle Passerotti ,&nbsp;Marianne E. Porter","doi":"10.1016/j.actbio.2025.08.002","DOIUrl":"10.1016/j.actbio.2025.08.002","url":null,"abstract":"<div><div>Shark skin is a biological composite of dermal denticles embedded in a multilayered network of collagen fibers. Variation of skin morphology (dermal denticles and collagen fibers) is observable among species, body regions, and developmental stages, and has been shown to relate to skin mechanics. The orientation of collagen fibers results in mechanical anisotropy; shark skin is more extensible when stressed longitudinally (anteroposterior) and stiffer when stressed perpendicularly (dorsoventral). To evaluate the impact of ecological and ontogenetic factors on mechanical behavior, we tested shark skin in uniaxial tension to failure and calculated the tensile strain and mechanical properties (strength, stiffness, and toughness) from 20 species, and quantified the effects of ecomorphotype and ontogeny, as well as stress axis and body region. The bonnethead shark <em>Sphyrna tiburo</em> was used as a case study to quantify mechanics in a single species across an ontogenetic series. We analyzed skin morphology and correlated this with mechanical behavior to understand the mechanisms that regulate skin function. Across ecomorphotypes, shark skin from deeper-water, non-migratory species (Ecomorphotype E) was stronger and tougher than skin from small-bodied, non-migratory species (Ecomorphotype B), and medium-bodied, migratory species (Ecomorphotype C) had stiffer skin than large-bodied, migratory species (Ecomorphotype D). We found skin from mature sharks was stronger, stiffer, tougher, and more extensible than skin from pups. These results indicate that ontogeny and ecomorphotype impact skin mechanics among sharks. Despite morphological diversity, aspects of skin morphology appear to play less of a role in regulating mechanical function.</div></div><div><h3>Statement of significance</h3><div>The current study establishes a comparative framework for evaluating the mechanical properties of shark skin across ecologically and morphologically diverse species, for which the mechanical behavior of the skin has not been investigated. The results advance our understanding of effective modulation of skin mechanics across functional groups and life stages, allow for improved comparisons of mechanical behavior among marine organisms, and provide insight into the adaptive design of biological materials in marine environments.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 470-486"},"PeriodicalIF":9.6,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850009","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":"Synergistic supramolecular conductive dressing integrating electrical stimulation and polyoxometalate antioxidants for enhanced chronic wound healing","authors":"Wei Wang ,&nbsp;Fengwei Sun ,&nbsp;Fuhong Yang ,&nbsp;Chen Cui,&nbsp;Bo Wang,&nbsp;Yanli Huang,&nbsp;Xianzeng Zhang,&nbsp;Zhen Yang","doi":"10.1016/j.actbio.2025.08.012","DOIUrl":"10.1016/j.actbio.2025.08.012","url":null,"abstract":"<div><div>Chronic wounds, exacerbated by bacterial infections and oxidative stress, remain a formidable challenge in clinical wound management. Here, we introduce a multifunctional conductive dressing composed of polyvinyl alcohol (PVA), poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT: PSS), a citric acid–<em>β</em>-cyclodextrin supramolecular system, and cyclodextrin–polyoxometalates (CD-POM). This dressing integrates electrical stimulation (ES), antioxidative capacity, anti-inflammatory effects, and antibacterial efficacy to promote tissue regeneration. Its good mechanical robustness, strong adhesion, and optimized electrical conductivity arise from synergistic interactions among PVA, PEDOT: PSS, and the supramolecular system. Moreover, the addition of CD-POM enables efficient scavenging of reactive oxygen species, thereby mitigating oxidative damage and creating a favorable healing microenvironment. ES further enhances fibroblast proliferation, migration, and angiogenesis, while simultaneously disrupting bacterial biofilms and boosting antibacterial performance. In vitro and in vivo evaluations confirm that the conductive dressing significantly accelerates wound closure, reduces inflammation, and promotes collagen deposition. Altogether, this study presents a promising bioelectronic wound dressing strategy that addresses both bacterial infections and oxidative stress, offering an advanced therapeutic platform for chronic wound management.</div></div><div><h3>Statement of Significance</h3><div>Chronic wounds are characterized by persistent bacterial infection and excess reactive oxygen species (ROS), which impair tissue regeneration. While conductive hydrogels with electrical stimulation (ES) have emerged as promising wound therapies, few address the oxidative stress inherent to inflamed wounds. Here, we present a supramolecular conductive gel (SPPCP) combining ES capability with ROS scavenging via cyclodextrin-polyoxometalates (CD-POM). This dual-functional strategy overcomes a key limitation of current bioelectronic dressings. SPPCP exhibits robust mechanical performance, strong adhesion, and enhanced antibacterial and antioxidative effects. In vivo results confirm accelerated healing, reduced inflammation, and improved angiogenesis. This work introduces a bioelectronic dressing paradigm tailored for oxidative microenvironments, of strong interest to researchers in smart wound care, redox biology, and advanced materials.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 340-353"},"PeriodicalIF":9.6,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144823388","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-laden vascular grafts orchestrate the optimization of the inflammatory microenvironment for abdominal aorta regeneration","authors":"Shutong Li ,&nbsp;Chenxi Huang ,&nbsp;Yijie He ,&nbsp;Xinyu Lei ,&nbsp;Xiaoyan Shen ,&nbsp;Jialin Xu ,&nbsp;Yunfei Mo ,&nbsp;Xiuhong Sun ,&nbsp;Ling Zheng ,&nbsp;Yuqing Niu","doi":"10.1016/j.actbio.2025.08.016","DOIUrl":"10.1016/j.actbio.2025.08.016","url":null,"abstract":"<div><div>The earliest tissue-engineered vascular grafts (TEVGs) applied clinically are biodegradable scaffolds laden with bone marrow mononuclear cells (BMCs). However, the inability to control BMCs fate after transplantation severely restricts their clinical use. To overcome this limitation, we developed a regenerative TEVG and investigated its role in modulating the immune microenvironment at arterial defects sites to enhance tissue regeneration. This TEVG was fabricated from a degradable elastomeric nanofiber scaffold combined with rBMCs, which had been induced to differentiate into regenerative M2 macrophages through <em>in vitro</em> culture. The resulting M2-derived extracellular matrix (ECM) dynamically modulated scaffold elasticity to match the biomechanical environment of the implantation site. When implanted into a rat abdominal aortic (rAA) defect model, the TEVGs, serving as interpositional artery grafts, could maintain the patency of abdominal artery blood circulation in rats and gradually transform into mature abdominal arteries within 12 months. However, the implanted rBMCs migrated away shortly after implantation. Instead, the scaffolds were initially repopulated by rat monocytes and subsequently gradually replaced by rat endothelial cells (ECs) and smooth muscle cells (SMCs). Further research revealed that the implanted M2 macrophages secrete IL-10 and IL-4, activating CD4⁺ <em>T</em> cells and initiating the Th2 pathway. IL-4 derived from Th2 cells sustained the M2 macrophages phenotype, forming a positive feedback loop that boosted the regenerative microenvironment-key to restoring arterial function. These findings suggest that integrating BMCs into vascular grafts and regulating the extracellular microenvironment may offers a practical and efficient strategy for treating damaged and diseased arteries.</div></div><div><h3>Statement of significance</h3><div>The earliest clinically applied tissue-engineered vascular grafts (TEVGs) are biodegradable scaffolds seeded with bone marrow mononuclear cells (BMCs), but the uncontrolled fate of BMCs after transplantation restricts their clinical use. This study developed a regenerative TEVG combining a degradable elastic nanofiber scaffold with <em>in vitro</em>-induced M2 macrophages. In a rat model, the TEVG maintained arterial patency and transformed into mature arteries within 12 months by activating an M2/Th2 immune positive feedback loop, offering a new strategy for arterial injury treatment.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 323-339"},"PeriodicalIF":9.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818596","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":"Super-small zwitterionic nitric oxide-donor micelles efficiently scavenge ROS and alleviate inflammation for combined ischemic stroke therapy","authors":"Ke Wang ,&nbsp;Yuli Ao ,&nbsp;Yiqing Xiao,&nbsp;Yi Wang,&nbsp;Xiaoping Liang,&nbsp;Mingxuan Zhao,&nbsp;Dongyu Zhang,&nbsp;Yinan Zhong,&nbsp;Hongliang Qian,&nbsp;Bingbing Zhao,&nbsp;Wei Chen","doi":"10.1016/j.actbio.2025.08.013","DOIUrl":"10.1016/j.actbio.2025.08.013","url":null,"abstract":"<div><div>Ischemic stroke has severely threatened the health of human beings, attributed to blood-brain barrier (BBB) damage, excess reactive oxygen species (ROS), and inflammation effect, which trigger neuronal death and impairment of neurological function. Herein, atorvastatin (ATO)-encapsulated super-small nitric oxide (NO)-donor micelles (M-NO@A) based on hyper-branched polyzwitterion are developed to reverse brain injury status and reduce infarct size. M-NO@A upon super-small volume can significantly accumulate in the ischemic region, thereby inhibiting the adhesion of inflammatory cells' to BBB by NO decreasing the expression of intracellular cell adhesion molecule-1 (ICAM-1) on BBB. Additionally, the introduction of NO is adequate to suppress inflammation amplification, in a combination with ATO-mediated oxidative stress reduction to maintain the brain's health synergistically. Meanwhile, significant reduction in cerebral infarct area and marked improvement in neurological function are clearly visualized in transient middle cerebral artery occlusion/reperfusion (tMCAO/R) models treated with M-NO@A. Consequently, these micelles provide a multifaceted strategy for drug delivery to damaged brains, thereby achieving efficient treatment of brain diseases.</div></div><div><h3>Statement of significance</h3><div>The designed atorvastatin (ATO)-encapsulated super-small nitric oxide (NO)-donor micelles (M-NO@A) utilize their ultra-small size and carboxybetaine (CB) functionalization to facilitate efficient blood-brain barrier (BBB) penetration and subsequent brain accumulation. This formulation effectively inhibits inflammatory cell adhesion to the BBB through nitric oxide (NO)-mediated downregulation of intercellular adhesion molecule-1 (ICAM-1) expression. Furthermore, the incorporated NO effectively suppresses inflammatory amplification, while ATO-mediated oxidative stress reduction synergistically preserves brain homeostasis. In transient middle cerebral artery occlusion/reperfusion (tMCAO/R) models, M-NO@A treatment demonstrated significant reductions in cerebral infarct volume and substantial improvements in neurological function. Collectively, these nanomicelles represent a multifaceted therapeutic strategy for targeted drug delivery to the injured brain, offering an effective approach for treating cerebrovascular disorders.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 547-557"},"PeriodicalIF":9.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818597","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":"Calcium phosphate-mineralized nanoplatform for enhanced ferroptosis and synergistic anti-PDL1 therapy in triple-negative breast cancer through multi-pathway targeting","authors":"Xiaokang Zhu ,&nbsp;Li Xie ,&nbsp;Qing Liao ,&nbsp;Jinming Tian ,&nbsp;Jinlin Peng ,&nbsp;Zhu Chen ,&nbsp;Erqun Song ,&nbsp;Yang Song","doi":"10.1016/j.actbio.2025.08.014","DOIUrl":"10.1016/j.actbio.2025.08.014","url":null,"abstract":"<div><div>Ferrotherapy has risen as a promising therapeutic approach for triple-negative breast cancer (TNBC); however, its potency is frequently compromised due to tumor cells’ ability to evade ferroptosis <em>via</em> various resistance pathways and insufficient immunogenicity. To overcome these limitations, we have engineered a calcium phosphate-mineralized ferroptosis inducer nanoplatform, termed Lf-PEG-CaP@iFSP1-Brequinar-Erastin-Fe³⁺-TA (LP-CaP@iBEFT), designed to augment ferroptosis by simultaneously targeting three key pathways: glutathione peroxidase 4 (GPX4), ferroptosis suppressor protein 1 (FSP1), and dihydroorotate dehydrogenase (DHODH). Once internalized and reached the acidic tumor microenvironment (TME), the nanoplatform discharges its therapeutic payloads, comprising inhibitors of FSP1 (iFSP), brequinar, erastin, and iron ions. The first three components were tailored to inhibit key pathways to ferroptosis, while the released iron ions initiate ferroptosis by catalyzing the generation of reactive oxygen species (ROS) <em>via</em> Fenton reactions. The calcium phosphate-mineralized ferroptosis inducer nanoplatform promotes the maturation of DC cells, enhances the infiltration of T cells and releases immunity-related factors, thereby altering the immunosuppressive microenvironment. In conjunction with anti-PD-L1 therapy, LP-CaP@iBEFT boosts T lymphocyte-mediated immune infiltration, thereby amplifying the anti-tumor response and offering a therapeutic approach for TNBC.</div></div><div><h3>Statement of significance</h3><div>We developed an acid-responsive nanoplatform that specifically targets tumor cells that overexpress lactoferrin receptors. This nanoplatform degrades within the acidic tumor environment to release the payload components iFSP1, brequinar, erastin, and Fe³⁺, which collectively inhibit three pathways of ferroptosis. This approach effectively dismantles the “triple defense” mechanism that tumor cells employ to resist ferroptosis. In addition, this nanoplatform synergizes with anti-PD-L1 immune checkpoint blockade, enhancing the T cell-mediated destruction of tumor cells.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 610-623"},"PeriodicalIF":9.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818593","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":"Characterization of stability and shell elasticity of monodisperse microbubbles with different pegylated-lipid content using pressure-dependent attenuation spectra","authors":"Hongyi Zhang ,&nbsp;Chang Lu ,&nbsp;Alfred C.H. Yu ,&nbsp;Peng Qin","doi":"10.1016/j.actbio.2025.08.017","DOIUrl":"10.1016/j.actbio.2025.08.017","url":null,"abstract":"&lt;div&gt;&lt;div&gt;The stability and acoustic-induced oscillation of microbubbles strongly depend on their shell properties. Determining the relationships between the shell composition and bubble stability and shell elasticity is crucial for improving microbubble-based ultrasound imaging and therapy. We used a flow-focusing microfluidic to fabricate monodisperse microbubbles with a primary lipid and pegylated-lipid at different molar ratios. The lipid density on the shell was regulated via the ambient pressure. The measured pressure-dependent resonance-frequency curve was used to characterize bubble states (i.e., elasticity, rupture, buckling, elastic–rupture transition, and elastic–buckling transition). Further, by tracking pressure-dependent resonance-frequency curves over time during dissolution, the rate of bubble dissolution (i.e., stability) was quantified. The surface-area-dependent elasticity was obtained by fitting the bubble oscillation model to the measured pressure-dependent attenuation spectra. With decreasing molar fraction of pegylated-lipid, the evolution rate of microbubbles from the elasticity to elastic–buckling regimes gradually increased, corresponding to a decrease in stability of microbubbles. Upon bubble expansion, the elasticity first peaked, then decreased to the elasticity–rupture transition point, followed by a quick decrease to the rupture regime. Upon bubble compression, the elasticity plateaued until the elastic–buckling transition point, and then rapidly declined to the buckling regime. Significantly lower elasticity was found in microbubbles with 5 %–10 % pegylated-lipid than those with 1 % and 2 %; above and below 5 %, the molar fraction did not affect the elasticity. This work represents a reliable and accurate approach to understand the bubble stability and shell viscoelastic mechanisms, and to tailor phospholipids for microbubble-based medical applications.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;Determining the relationships between shell composition, bubble stability and shell elasticity is critical for designing state-of-art microbubbles and improving ultrasound-based imaging and therapy. The pressure-dependent resonance-frequency curves over time was used to characterize monodisperse microbubble states (i.e., elasticity, rupture, buckling, elastic–rupture transition, and elastic–buckling transition) and to quantify the bubble dissolution rate (i.e., stability). With decreasing pegylated-lipid content on the shell, the bubble dissolution rate increased while stability decreased.&lt;/div&gt;&lt;div&gt;Additionally, the pressure-dependent attenuation spectra were used to characterize nonlinear surface-area-dependent elasticity. The chain configurations (e.g., mushroom or brush) of pegylated-lipid dominated shell elasticity. This work deepens the understanding of viscoelastic mechanisms of bubble shell, and provides a systematic approach to tailor shell compositions for optimized microbubble-based medical applicatio","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 596-609"},"PeriodicalIF":9.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818594","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":"The Mo-14Re alloy, a promising candidate material for bioresorbable vascular scaffolds","authors":"Chi Zhang ,&nbsp;Yiqiang Li ,&nbsp;Yibo Zhang ,&nbsp;Jian Xue ,&nbsp;Xiaohui Lin ,&nbsp;Yanchao Li ,&nbsp;Dongxu Wang ,&nbsp;Jinlong Liu ,&nbsp;Gaosen Zhang ,&nbsp;Haoyang Jiang ,&nbsp;Meng Niu ,&nbsp;Yang Chu ,&nbsp;Hongwei Zhao","doi":"10.1016/j.actbio.2025.08.015","DOIUrl":"10.1016/j.actbio.2025.08.015","url":null,"abstract":"<div><div>Zinc‑, iron‑, and magnesium‑based biodegradable metals suffer inherent limitations as bioresorbable scaffold materials, including inappropriate degradation rates and insufficient mechanical strength. Pure molybdenum (Mo) has been proposed as an alternative, but its clinical application is hampered by brittleness and potential nephrotoxicity. A Mo alloy was engineered to address these challenges. By alloying with rhenium (Re), Mo–14Re sheets and microwires with tunable mechanical properties were produced, achieving enhanced ductility in Mo‑based materials while retaining adequate strength for vascular stent applications. Importantly, Re addition not only enhances plasticity but also markedly reduces the degradation rate of Mo and diminishes Mo accumulation in biodegradation residues, thereby mitigating renal toxicity—a significant advancement for Mo‑based implants. The Mo–14Re alloy demonstrates biocompatibility and antimicrobial activity, and 12‑week <em>in vivo</em> tests confirmed complete endothelialization of Mo–14Re wires implanted in rat abdominal aortae. Whereas pure Mo induced severe glomerulosclerosis, Mo–14Re exhibited no detectable nephrotoxicity, effectively addressing the principal safety concern of Mo implants. These findings open new directions for the development of high‑performance biodegradable metals.</div></div><div><h3>Statement of significance</h3><div>This study introduced a Mo-14Re biodegradable alloy that addressed the key limitations of pure molybdenum for bioresorbable applications, including insufficient ductility, rapid degradation, and nephrotoxicity. Rhenium alloying significantly improved mechanical ductility, enhanced corrosion resistance, and reduced toxic molybdenum accumulation, while maintaining biocompatibility. <em>In vivo</em> experiments demonstrated complete endothelialization and no renal toxicity, establishing Mo–14Re as a promising candidate material for next-generation biodegradable vascular implants.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 657-673"},"PeriodicalIF":9.6,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818598","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":"Design of low-dose, non-hormonal female contraceptives targeting trophoblast cells using vitamin B13 copper metal-organic frameworks","authors":"Zhenning Su ,&nbsp;Jianlin Wang ,&nbsp;Cancan Yao ,&nbsp;Xihua Chen ,&nbsp;Bin He ,&nbsp;Xiangbo Xu ,&nbsp;Xiaoxue Xu ,&nbsp;Yufeng Zheng","doi":"10.1016/j.actbio.2025.08.007","DOIUrl":"10.1016/j.actbio.2025.08.007","url":null,"abstract":"<div><div>Unintended pregnancy remains a significant concern in women's healthcare. Although current short-term contraceptive methods, particularly hormonal approaches, are effective in preventing unintended pregnancy, their potential long-term adverse effects necessitate the development of safer alternatives. A nanostrategy that interrupts early pregnancy by inhibiting embryonic trophoblast cell proliferation presents a promising non-hormonal approach with minimal adverse effects on female reproductive system. In this study, we further advanced this strategy by designing a highly effective, low-dose contraceptive using vitamin B13 copper metal-organic framework (VB13 Cu-MOF) as the active agent. VB13 Cu-MOF exhibited rapid dissolution in aqueous environments with a sustained and low Cu²⁺ release rate, facilitating preferential uptake by embryonic trophoblast cells due to their tumor-like characteristics. Upon contact with cells in the in vitro cellular model, the released Cu²⁺ was transported into cells via proteins on cell membrane in two pathways, direct Cu²⁺ intracellular transport, and Cu²⁺ reduction to Cu⁺ and Cu⁺ intracellular transport. Both Cu²⁺ and Cu⁺ in cells triggered parallel Fenton-like reactions, resulting in excessive reactive oxygen species generation, mitochondrial damage, apoptosis, and ferroptosis. RNA-seq analysis identified the key biological processes and the associated genes involved in these interactions. In vivo experiments in rat models demonstrated contraceptive efficacy using VB13 Cu-MOF at an ultra-low dose (65 μg/mL) and its hydrogel formulation, without inducing adverse effects on serum copper levels, estrogen concentrations, inflammatory markers, or organ morphology. These findings establish VB13 Cu-MOF as a promising non-hormonal contraceptive with strong potential to prevent unintended pregnancies while minimizing risks to women's health.</div></div><div><h3>Statement of significance</h3><div>Vitamin 13 copper metal-organic Framework (VB13 Cu-MOF) was designed and developed as a bioactive material for female non-hormonal contraceptives. As a new source of copper ions, VB13 Cu-MOF demonstrated a controlled release of copper ions, effectively targeting and inducing trophoblast cell death to achieve high contraceptive efficacy in a rat model at low dosage, without causing adverse effects in vitro or in vivo. Moreover, VB13 can increase the histocompatibility of Cu-MOF to normal cells. VB13 Cu-MOF was employed to validate a novel contraceptive mechanism targeting trophoblast cells to interrupt the pregnancy process 5–8 days after mating. Significantly, this demonstrates its potential as a promising non-hormonal contraceptive for clinical use, contributing to enhanced women's healthcare.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 624-642"},"PeriodicalIF":9.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812761","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":"Biomaterial-based 3D human lung models replicate pathological characteristics of early pulmonary fibrosis","authors":"Alicia E. Tanneberger ,&nbsp;Rachel Blomberg ,&nbsp;Anton D. Kary ,&nbsp;Andrew Lu ,&nbsp;David W.H. Riches ,&nbsp;Chelsea M. Magin","doi":"10.1016/j.actbio.2025.08.010","DOIUrl":"10.1016/j.actbio.2025.08.010","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Idiopathic pulmonary fibrosis (IPF) is a progressive and incurable lung disease characterized by tissue scarring that disrupts gas exchange. Epithelial cell dysfunction, fibroblast activation, and excessive extracellular matrix deposition drive this pathology that ultimately leads to respiratory failure. Mechanistic studies have shown that repeated injury to alveolar epithelial cells initiates an aberrant wound-healing response by surrounding fibroblasts through secretion of mediators like transforming growth factor beta (TGF- β), yet the precise biological pathways contributing to disease progression are not fully understood. To better study these interactions there is a critical need for lung models that replicate the cellular heterogeneity, geometry, and biomechanics of the distal lung microenvironment. In this study, induced pluripotent stem cell-derived alveolar epithelial type II (iATII) cells and human pulmonary fibroblasts were arranged to replicate key features of human lung micro-architecture and embedded in soft or stiff poly(ethylene glycol) norbornene (PEG-NB) hydrogels that recapitulated the mechanical properties of healthy and fibrotic lung tissue, respectively. The co-cultured cells were then exposed to pro-fibrotic cytokines and growth factors. iATIIs and fibroblasts exhibited differentiation pathways and gene expression patterns consistent with trends observed during IPF progression &lt;em&gt;in vivo&lt;/em&gt;. A design of experiments statistical analysis identified stiff hydrogels combined with pro-fibrotic biochemical cue exposure as the most effective condition tested in this study for modeling fibrosis &lt;em&gt;in vitro&lt;/em&gt;. Finally, treatment with Nintedanib, one of only two Food and Drug Administration (FDA)-approved drugs for IPF, was assessed. Treatment reduced fibroblast activation, as indicated by downregulation of key activation genes, and upregulated several epithelial genes involved in alveolar repair. These findings demonstrate that human 3D co-culture models hold are a promising tool for advancing our understanding of IPF and identifying new therapeutic targets.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;This study leverages advanced biomaterials and biofabrication techniques to engineer physiologically relevant, donor-specific, and sex-matched models of pulmonary fibrosis, addressing the critical need for pre-clinical therapeutic drug screening platforms. These human 3D lung models successfully replicated key features of fibrotic lung tissue. Tuning microenvironmental stiffness of 3D PEG-NB hydrogels to match fibrotic lung values and exposing human iATII cells and fibroblasts to pro-fibrotic biochemical cues recreated hallmark characteristics of &lt;em&gt;in vivo&lt;/em&gt; fibrosis pathogenesis, including epithelial differentiation and loss, as well as fibroblast activation. The utility of these models was further validated by demonstrating responsiveness to Nintedanib, a clinically available treatment for IPF. These","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 277-292"},"PeriodicalIF":9.6,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812727","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":"Macroporous hydrogel-based mRNA cancer vaccine for in situ recruitment and modulation of dendritic cells","authors":"Jiadiao Zhou ,&nbsp;Yusheng Liu ,&nbsp;Wenhao Xu ,&nbsp;Rimsha Bhatta ,&nbsp;Joonsu Han ,&nbsp;Dhyanesh Baskaran ,&nbsp;Savindi Devmal ,&nbsp;Cecilia Leal ,&nbsp;Hua Wang","doi":"10.1016/j.actbio.2025.08.005","DOIUrl":"10.1016/j.actbio.2025.08.005","url":null,"abstract":"<div><div>mRNA-based vaccines have demonstrated tremendous success in the era of covid-19, but their full potential for cancer treatment awaits to be realized. To address the low efficiency of conventional mRNA vaccines to encounter and become taken up by dendritic cells in the body, here we report a macroporous hydrogel-based mRNA vaccine that enables <em>in situ</em> recruitment and modulation of dendritic cells. Upon subcutaneous injection of macroporous hydrogels loaded with chemokines and neoantigen-encoding mRNA lipoplexes, high numbers of dendritic cells can be recruited to the gel, take up and process mRNA, and present mRNA-encoded neoantigens <em>in situ</em>, prior to their migration to draining lymph nodes to prime neoantigen-specific CD8⁺ <em>T</em> cells. The gel vaccine significantly enhances the cytotoxic T lymphocyte response and antitumor efficacy against E.G7-OVA lymphoma and 4T1 breast cancer. Our dendritic cell-homing gel-based mRNA vaccine provides a new and universal avenue to enhancing the antitumor efficacy of mRNA vaccines.</div></div><div><h3>Statement of Significance</h3><div>Current mRNA cancer vaccines are typically formulated by incorporating tumor antigen-encoding mRNAs into lipid nanoparticles (LNPs) or condensing them with cationic polymers or lipids, which are then directly administered into the body. These formulations rely on the passive uptake of mRNA by antigen-presenting cells, mainly dendritic cells (DCs), in lymphatic tissues, but the efficiency of this process is often low. To address this limitation, we developed a DC-homing macroporous hydrogel-based mRNA vaccine that actively recruits DCs and enables <em>in situ</em> processing of pre-loaded mRNA lipoplexes, leading to enhanced cytotoxic T lymphocyte responses and antitumor efficacy. Our DC-homing gel-based mRNA vaccine provides a modular approach to enhancing the antitumor efficacy of mRNA vaccines for treating various types of cancers.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 234-245"},"PeriodicalIF":9.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144801208","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}