Acta Biomaterialia最新文献

{"title":"Paralytic peptide reduces hemolymph viscoelasticity and promotes bulk-initiated coagulation in hornworm Manduca sexta","authors":"Artis Brasovs, M.A. Nozzari Varkani, Jinbo Song, Yang Wang, Haobo Jiang, Konstantin G. Kornev","doi":"10.1016/j.actbio.2026.08.026","DOIUrl":"10.1016/j.actbio.2026.08.026","url":null,"abstract":"<div><div>Hemolymph coagulation is a vital component of insect immunity, rapidly reducing fluid loss and limiting pathogen spread after injury. In <em>Manduca sexta</em> larvae, paralytic peptide (PP) is a fast-acting cytokine activated by an unknown serine protease, and its influence on hemolymph mechanics remains largely unexplored. Here, we examine how PP exposure alters the extensional and surface rheological properties of larval hemolymph, providing insight into the physical manifestation of the immune activation. Hemolymph collected from fifth-instar larvae exhibited weak viscoelastic behavior in 84% of extensional rheology experiments, with a mean characteristic relaxation time of <span><math><mrow><mn>1.9</mn><mspace></mspace><mo>±</mo><mspace></mspace><mn>1.5</mn><mspace></mspace><mi>m</mi><mi>s</mi></mrow></math></span>. Treatment with 10 μM PP resulted in a pronounced shift toward a more Newtonian-like behavior: only 63% of samples remained viscoelastic, and the mean relaxation time (<span><math><mrow><mn>0.7</mn><mo>±</mo><mspace></mspace><mn>0.6</mn><mspace></mspace><mi>m</mi><mi>s</mi></mrow></math></span>) (<span><math><mrow><mi>p</mi><mo><</mo><mn>0.001</mn></mrow></math></span>) was reduced by >2-fold. In samples subjected to repeated measurements, PP exposure caused a rapid loss of viscoelasticity on the timescale of seconds. Surface rheology was probed using magnetic rotational spectroscopy with magnetic microrods. In hemolymphs aged for > 10 min, the surface layer of untreated and PP-treated hemolymphs behaved as a Maxwellian viscoelastic fluid. The relaxation time of the viscoelastic reaction is measured in seconds, i.e., it is three orders of magnitude larger than that in the bulk. The surface drag coefficients of the microrods on PP-treated hemolymph are about twofold smaller than those of untreated ones. As the hemocyte aggregation ceased in <span><math><mrow><mo>∼</mo><mn>10</mn></mrow></math></span> min after hemolymph extraction, these rheological signatures suggest that PP-stimulated coagulation initiates within the bulk hemolymph.</div></div><div><h3>Statement of significance</h3><div>Hemolymph coagulation is essential for insect survival, preventing fluid loss, pathogen invasion, and loss of mechanical support following injury. While molecular components of insect immune responses have been extensively studied, physical transformations of hemolymph during early wound responses remain poorly understood. Using extensional rheology and magnetic rotational spectroscopy, we show that a cytokine named paralytic peptide (PP), which is proteolytically activated after wounding, rapidly alters the viscoelastic properties of the hornworm <em>Manduca sexta</em> hemolymph. PP reduces bulk viscoelasticity within seconds and modifies interfacial rheological behavior, revealing a direct link between immune signaling and hemolymph mechanics. These findings provide new insight into how proteolytic enzyme(s) convert hemolymph ","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 408-420"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A bioactive polyurethane adhesive delivers interfacial mechano-biochemical cues for meniscus tear repair","authors":"Xiaolong Yang,&nbsp;Lin Yang,&nbsp;Shiji Gao,&nbsp;Yi Zhou,&nbsp;Zhe Xu,&nbsp;Junqiao Li,&nbsp;Jiehua Li,&nbsp;Hong Tan,&nbsp;Feng Luo,&nbsp;Weili Fu","doi":"10.1016/j.actbio.2026.09.004","DOIUrl":"10.1016/j.actbio.2026.09.004","url":null,"abstract":"<div><div>Meniscus repair is often limited by poor intrinsic healing, an adverse oxidative-inflammatory microenvironment, and insufficient mechanical continuity across the tear interface. Here, we engineered a solvent-free injectable polyurethane adhesive (PUA) loaded with connective tissue growth factor (PUA@CTGF) for meniscus tear repair that combines rapid wet interfacial stabilization, compliant defect filling, and prolonged CTGF release. The adhesive showed rapid <em>in situ</em> curing, high apparent initial wet lap-shear strength, and stable short-cycle compressive behavior in a 100-cycle loading–unloading test. <em>In vitro</em>, PUA@CTGF reduced oxidative stress-associated mitochondrial injury, modulated macrophage-associated inflammatory markers toward a more repair-supportive profile, promoted meniscal cell migration, and enhanced fibrochondrogenic matrix synthesis when combined with cyclic tensile stimulation. In a rabbit outer-vascular-zone meniscus tear model, PUA@CTGF improved repair-region continuity, matrix deposition, and tensile properties and attenuated early joint degenerative changes relative to untreated, suture, fibrin, and PUA controls, although native meniscal tensile properties were not fully restored during the 12-week observation period. Transcriptomic profiling identified mechanotransduction-related signatures, while inhibitor-supported <em>in vitro</em> analyses showed that GsMTx4 attenuated dynamic-loading-induced Ca²⁺ and YAP responses, supporting a GsMTx4-sensitive mechanotransduction response. These findings support PUA@CTGF as a bioactive polyurethane adhesive platform for wet, mechanically active meniscal repair interfaces.</div></div><div><h3>Statement of significance</h3><div>Meniscus tears are difficult to heal because the injured interface is wet, mechanically active, and biologically hostile. This study introduces a solvent-free injectable polyurethane adhesive that rapidly stabilizes wet meniscal tears while providing localized delivery of connective tissue growth factor. By combining catechol-assisted wet adhesion, compliant defect filling, short-cycle energy dissipation, reactive oxygen species buffering, and prolonged CTGF release, the adhesive provides interfacial stabilization and microenvironmental regulation. <em>In vitro</em> and rabbit studies showed enhanced cell migration and matrix-associated responses, improved repair-region continuity and tensile properties, and attenuation of early joint degenerative changes. This work advances biomaterial design by integrating wet interfacial stabilization with localized biochemical delivery for the repair of mechanically active, load-bearing soft-tissue interfaces.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 236-258"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148889705","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":"Magnesium phosphate minerals and cements as bone substitute materials","authors":"Friederike Kaiser,&nbsp;Lena Schröter,&nbsp;Anita Ignatius,&nbsp;Uwe Gbureck","doi":"10.1016/j.actbio.2026.01.019","DOIUrl":"10.1016/j.actbio.2026.01.019","url":null,"abstract":"<div><div>When bone defects surpass a critical threshold in size, they typically necessitate intervention through either autologous bone grafting or the use of synthetic substitutes to maintain structural support and prevent unwanted soft tissue infiltration. Most synthetic bone graft materials currently in use are composed of calcium phosphate compounds, such as hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP). Despite their widespread clinical adoption and long-standing research, these materials still face important limitations, including suboptimal mechanical strength and slow resorption, particularly in the case of HA. Magnesium phosphate (MgP) compounds have emerged as promising alternatives in this context. Their higher solubility compared to calcium phosphates and their encouraging performance in promoting bone regeneration, demonstrated even in large animal studies, suggest their potential as next-generation bone substitutes. This review focuses on the current state of research regarding MgP-based materials for bone repair. It explores fundamental aspects of MgP chemistry, how these materials can be processed into clinically applicable forms such as injectable cements, granules, or porous scaffolds, and examines their effects on bone healing in various preclinical animal models.</div></div><div><h3>Statement of significance</h3><div>Critical-sized bone defects remain a major clinical challenge, and despite decades of research, the synthetic substitutes most widely used today are hindered by limited resorption and suboptimal mechanical performance. Magnesium phosphate based biomaterials have recently emerged as promising next-generation bone substitutes due to their favorable resorption kinetics, high initial mechanical strength, bioactivity, and potential to actively support bone regeneration. This review critically evaluates the current state of knowledge on these materials, covering their chemistry, processing into cements, granules, and scaffolds, and preclinical in vivo outcomes. By integrating findings across different magnesium-based systems, the review highlights both opportunities and remaining challenges for translation into clinical practice.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"224 ","pages":"Pages 20-38"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiscale analysis reveals distinct temporal trajectories of morphological reconstruction and mechanical maturation during mouse digit tip regeneration","authors":"Hanwen Fan,&nbsp;Preston Nguyen,&nbsp;Zerrin Uzum,&nbsp;Julia Kehl,&nbsp;Xiaqiu Xiao,&nbsp;Julia Bell,&nbsp;Veda Manikonda,&nbsp;Jacob Zachary Chen,&nbsp;Van Anh Nguyen,&nbsp;Srikanth Sampathkumar,&nbsp;Noah Dover,&nbsp;Andrei Demkov,&nbsp;Morgan Lilly,&nbsp;Lindsay A. Dawson,&nbsp;Connor P. Dolan,&nbsp;Yuxiao Zhou","doi":"10.1016/j.actbio.2026.08.032","DOIUrl":"10.1016/j.actbio.2026.08.032","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Mouse digit tip regeneration offers a model for mammalian epimorphic regeneration, yet the spatiotemporal evolution between emerging tissue architecture and its mechanical environments remain poorly understood. In this study, we employed a multiscale approach, integrating &lt;em&gt;in vivo&lt;/em&gt; micro-CT imaging, atomic force microscopy (AFM) nanomechanical mapping, and finite element modeling (FEM), to quantitatively characterize the temporal evolution of structural organization, local nanomechanical properties, and tissue-scale mechanical environments throughout mouse digit tip regeneration following amputation. AFM measurements revealed distinct patterns of structural reconstruction during regeneration: while the proximal stump underwent rapid repair-associated ossification, the distal tip underwent blastema-driven regeneration characterized by the formation and progressive coalescence of discrete mineralized regions within a highly compliant extracellular matrix. Comparison of the multiscale measurements showed that structural reconstruction and local mechanical maturation progressed along distinct temporal trajectories, with gross anatomical continuity restored by 21 days post-amputation (DPA), whereas native-like local nanomechanical properties continued to mature through 28–31 DPA. FEM analyses further showed progressive restoration of dorsal–ventral stress symmetry during regeneration, with the ventral-to-dorsal mechanical stress and strain ratio approaching the near-unity value observed in unamputated digits, while evolving distal geometry progressively altered stress distributions within the regenerated bone. Together, these findings establish a quantitative multiscale dataset for comparing structural reconstruction, local mechanical maturation, and the evolution of tissue-scale mechanical environments throughout digit regeneration. This multiscale perspective provides a quantitative reference for evaluating functional recovery and may inform the development of bio-inspired strategies for enhancing musculoskeletal regeneration in non-regenerative contexts.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;Mammalian digit tip regeneration is a model of complex tissue regrowth, yet how structural organization, local mechanical properties, and tissue-scale mechanical environments evolve during regeneration remains poorly understood. Here, we integrate &lt;em&gt;in vivo&lt;/em&gt; micro-CT imaging, atomic force microscopy, and finite element modeling to quantitatively characterize the multiscale structural and mechanical evolution of regenerating mouse digits. Our findings show that structural reconstruction, local matrix maturation, and tissue-scale mechanical environments evolve over distinct spatial and temporal patterns throughout regeneration, providing quantitative insight into the progression of matrix organization and mechanical function. This multiscale framework establishes a quantitative basis for investigating mechanobiological regu","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 341-353"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controlling viscoelastic behavior and microstructural organization in engineered living materials using synthetic adhesins and rheometry","authors":"Stefana A. Costan,&nbsp;Kira M. Hallerbach,&nbsp;Samuel Y. Kim,&nbsp;Chris Camp,&nbsp;Minkyu Kim,&nbsp;Ingmar H. Riedel-Kruse","doi":"10.1016/j.actbio.2026.08.044","DOIUrl":"10.1016/j.actbio.2026.08.044","url":null,"abstract":"<div><div>Engineered living materials (ELMs) at the multicelluar level represent an innovation that promises programmable properties for various applications. However, the rational tuning of the mechanical properties of such ELMs from first principles remains a challenge. Here we use synthetic cell–cell adhesins to systematically characterize how rheological and viscoelastic properties of multicellular materials made from living bacteria can be tuned through adhesion strength, cell size, cell shape, and adhesion logic. We find that many of the previous results obtained for non-living materials also apply to bacterial ELMs. Additionally, the incorporation of synthetic adhesins, combined with the adaptability of bacterial cells in modifying various cellular parameters, constitutes a new approach for the precise control over material properties. Furthermore, we demonstrate that rheology is a powerful tool for actively shaping the microscopic structure of ELMs, enabling control over cell aggregation and particle rearrangement, a key feature for complex material design. These results deepen our understanding of tuning the viscoelastic properties and fine structure of ELMs for bioprinting, microbial consortia design, and biomedical applications.</div><div><em>Statement of significance:</em> The fields of Engineered Living Materials (ELMs) and Synthetic biology undergo rapid synergistic advancements, with bacterial and eukaryotic cells serving as modular building blocks for programmable materials. A critical challenge lies in the precise control and tunability over the mechanical and structural properties of ELMs. This paper demonstrates (1) the tunability of material viscoelasticity through key cellular parameters, i.e., adhesin strength, adhesion logic, cell shape, and multi-component mixing ratios; and (2) the generation of spatially defined colloidal consortia, mesoscopic structuring, pore formation and defect minimization through rheological manipulations. This paper bridges gaps between synthetic biology and materials science by providing a quantitative basis for ELM design and characterization, and by extending results from non-living particle suspensions to ELMs.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 376-386"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovations in foot and ankle arthrodesis: Biological and biomaterial approaches to reducing non-union and the challenge of preclinical models","authors":"Yueying Xiao,&nbsp;Janos M. Kanczler,&nbsp;Jonathan I. Dawson,&nbsp;Togay Koç","doi":"10.1016/j.actbio.2026.01.026","DOIUrl":"10.1016/j.actbio.2026.01.026","url":null,"abstract":"<div><div>Foot and ankle arthrodesis remains a critical surgical approach for managing end-stage joint disease, yet its success is frequently hindered by the challenge of non-union. Despite advances in surgical techniques, complex cases – such as tibiotalocalcaneal fusion – still face non-union rates as high as 27 %, largely due to the region’s unique biomechanical demands and compounded by patient comorbidities and surgical variability. In recent years, orthobiologics and advanced biomaterials have demonstrated significant promise in enhancing fusion outcomes, particularly in high-risk patients with bone defects, metabolic disorders, or a history of infection. However, much of the existing clinical evidence stems from other orthopaedic contexts, with limited high-quality data specific to foot and ankle applications. To bridge this gap and support translational innovation, the development of preclinical models that accurately replicate the physiological and pathological characteristics of the human foot and ankle is essential. This review provides a comprehensive overview of the latest advancements in biologics and biomaterials for foot and ankle arthrodesis, with particular emphasis on hydrogels as next-generation platforms for bone regeneration and targeted drug delivery. Additionally, we critically examine the limitations of current preclinical models in terms of biomechanical compatibility and pathological relevance, highlighting opportunities for future refinement.</div></div><div><h3>Statement of significance</h3><div>Foot and ankle arthrodesis often fails due to non-union in complex, poorly vascularized regions. Emerging biomaterials, such as B2A-coated ceramics and peptide-enhanced grafts, show promise in enhancing fusion outcomes. However, a critical barrier to translation is the lack of preclinical models that reflect the foot and ankle’s pathological and mechanical complexity. This review not only surveys advanced orthobiologics but also proposes strategies for developing “negative models” and integrating high-risk conditions to better evaluate fusion efficacy. By bridging biomaterial innovation with model development, it offers a structured path for future research and clinical translation in foot and ankle fusion.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"224 ","pages":"Pages 256-271"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992274","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":"Modelling disc degeneration-induced neurovascular invasion on a chip for chronic low back pain therapeutic testing","authors":"Sandhya Natesan,&nbsp;Tarun Shyam Mohan,&nbsp;Mayank Singh,&nbsp;Pavan Pandit,&nbsp;G.L. Samuel,&nbsp;Greeshma Thrivikraman","doi":"10.1016/j.actbio.2026.05.037","DOIUrl":"10.1016/j.actbio.2026.05.037","url":null,"abstract":"<div><div>Intervertebral disc (IVD) degeneration is the most common musculoskeletal disorder worldwide. Yet, the underlying pathological processes remain largely unclear, primarily due to the lack of suitable in vitro models that accurately replicate the complex interactions of vascular and neural growth, inflammatory cytokine secretion, and immune cell infiltration that contribute to disc degeneration. To address this gap, we developed an affordable microfluidic IVD model using a 5-axis computer numerical control (CNC) micromilling machine with a multi-chamber culture design featuring a central disc zone divided by micropillars to accommodate nucleus pulposus (NP) and annulus fibrosus (AF). The design also incorporates two peripheral zones for co-culturing neurovascular units, separated by radial microgratings to maintain the avascular and aneural milieu of healthy discs. Under healthy conditions, our microfluidic device effectively restricted the migration of neural and endothelial cells when co-cultured with NP cells. Conversely, upon IL-1β-induced inflammation, we observed significant neural (325 ± 209 µm) and endothelial (884 ± 214 µm) cell migration towards the NP cells. Beyond neurovascular invasion, our IVD-on-a-chip provided valuable insights into immune cell dynamics, revealing that M1 macrophage infiltration, not just neovascularization, plays a key role in the progression of disc degeneration. Strikingly, our findings revealed that therapeutic interventions using glycosaminoglycan supplementation and celecoxib treatment resulted in a fourfold reduction in macrophage infiltration and over a twentyfold decrease in neural invasion compared to the inflamed control group. This highlights the potential of our system for drug testing aimed at preventing neovascularization and innervation, which are typically associated with discogenic pain.</div></div><div><h3>Statement of significance</h3><div>Most spine abnormalities are directly linked to intervertebral disc (IVD) degeneration, accounting for 40–50% of chronic lower back pain cases, often leading to lumbar disc prolapse, radiculopathy, spinal stenosis, and myelopathy. In fact, many aspects of the mechanisms behind disc degeneration remain elusive due to the lack of in vitro models replicating the complex inflammatory and catabolic processes involved. Hence, this study presents an improved micro-physiological IVD-on-a-chip platform that captures key characteristics of symptomatic disc degeneration, starting with inflammatory cytokine-induced nucleus pulposus dysregulation, neovascularization, macrophage infiltration, and sensory neuron ingrowth. The developed IVD-on-a-chip system offers new capabilities for investigating local degenerative responses that drive disc-related pain, serving as a high-throughput platform for testing potential drugs inhibiting complex neuro-immuno-vascular interactions.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"224 ","pages":"Pages 239-255"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019211","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":"pH-Responsive double-network Janus hydrogel incorporates tannic acid–iron nanoparticles for chronic wound healing and monitoring","authors":"Qingche Pan,&nbsp;Xinwei Tao,&nbsp;Jianliang Li,&nbsp;Tianle Zhou,&nbsp;Huaping Tan","doi":"10.1016/j.actbio.2026.08.055","DOIUrl":"10.1016/j.actbio.2026.08.055","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Polyacrylic acid-based composites hold substantial promise for intelligent wound dressing applications, owing to their intrinsic hydrophilicity and pH responsiveness. Nevertheless, their clinical translation is hindered by insufficient mechanical properties and excessive adhesion, which are directly induced by high hydrophilicity. Herein, a dual-network Janus hydrogel based on polyacrylic acid (PAA) and sodium alginate (SA), denoted as tannic acid–iron nanoparticles@polyacrylic acid/sodium alginate (TA-Fe NPs@PS Janus), was rationally fabricated. This hydrogel incorporates self-assembled TA-Fe nanoparticles (TA-Fe NPs) with inherent antibacterial activity and magnetic responsiveness. Magnetic enrichment of nanoparticles at the bottom side of the hydrogel not only significantly enhances mechanical toughness via metal–phenolic network (MPN) but also renders the top and bottom layers with distinct intelligent responses to heterogeneous pH microenvironments, thus enabling effective antibiotic-free treatment of infected wounds. TA-Fe NPs@PS Janus integrates high mechanical toughness, sensing performance, and pH responsiveness, enabling monitoring of wound microenvironmental changes through combined responses to pH and ionic variations throughout the recovery process. The physicochemical, mechanical, and rheological properties of the hydrogel were systematically characterized, and &lt;em&gt;in vitro&lt;/em&gt; antibacterial assessments were conducted. Results demonstrate that TA-Fe NPs significantly enhance hydrogel toughness: compared with the pristine PAA/SA hydrogel (PS), the composite hydrogel incorporating 0.3% (w/v) TA-Fe NPs exhibits a 1200% increase in tensile toughness (from 0.06 MJ m⁻³ to 0.78 MJ m⁻³). The hydrogel displays high sensitivity and undergoes reversible deformation and intelligent responsive behavior under cyclic pH changes. It not only exhibits high antibacterial efficacy but also demonstrates favorable cytocompatibility. Therefore, this study proposes a smart, stimuli-responsive multifunctional hydrogel dressing for treating chronic wound inflammation and monitoring the healing process, highlighting its potential for clinical applications.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of significance&lt;/h3&gt;&lt;div&gt;Chronic infected wounds severely threaten human health, yet clinically viable smart wound dressings are lacking. Polyacrylic acid (PAA) hydrogels are attractive for wound management but suffer from poor mechanical toughness and over-adhesion. We fabricate a dual-network Janus hydrogel (TA-Fe NPs@PS Janus) incorporating PAA, sodium alginate and tannic acid-iron nanoparticles. Magnetically concentrated TA-Fe NPs form metal-phenolic networks, boosting toughness by 1044.2% and creating asymmetric pH responsiveness. This cytocompatible hydrogel achieves antibiotic-free antibacterial function and real-time infection monitoring via pH changes. It overcomes key drawbacks of PAA hydrogels, integrates diagnosis and therapy, and offers a translatable s","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 520-540"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875961","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 delivery of immunostimulatory oligonucleotides and doxorubicin by magnetic nanoparticles and metal-organic frameworks for antitumor immunotherapy","authors":"Jaesung Lim,&nbsp;Hee Seung Seo,&nbsp;Jun-Hyeok Han,&nbsp;Min Ji Byun,&nbsp;Chi-Pin James Wang,&nbsp;Sung Soo Park,&nbsp;Soo-Hyun Lee,&nbsp;Ha Eun Shin,&nbsp;Juwon Park,&nbsp;Gwang Yeol Park,&nbsp;Tae-Eun Park,&nbsp;Hee Ho Park,&nbsp;Tae-Hyung Kim,&nbsp;Cheol-Hwi Kim,&nbsp;Wooram Park,&nbsp;Chun Gwon Park,&nbsp;Se-Na Kim","doi":"10.1016/j.actbio.2026.08.028","DOIUrl":"10.1016/j.actbio.2026.08.028","url":null,"abstract":"<div><div>The immunosuppressive tumor microenvironment (TME) remains a major challenge to effective cancer immunotherapy. We hypothesized that combining dendritic cell (DC) maturation with immunogenic cell death (ICD) could enhance antitumor immunity by simultaneously providing immune-activating signals and tumor-associated antigens. To achieve this, we developed a dual-nanocarrier utilizing distinct nanoparticles: surface-modified magnetic nanoparticles (MNPs) for CpG oligodeoxynucleotide (CpG ODN) delivery and metal-organic frameworks (MOFs) for doxorubicin (DOX) encapsulation. Separate carriers of the two agents enabled independent control of their delivery functions. CpG-pMNPs promoted DC maturation more effectively than an equivalent dose of free CpG ODN, whereas DOX@UiO-67 induced ICD. In breast tumor model, the combined treatment markedly suppressed tumor growth and prolonged survival. Immune profiling further showed increased matured DC in tumor-draining lymph nodes, enhanced tumor infiltration of T cells and cytotoxic T lymphocytes, and modulation of immunosuppressive immune populations. In the spleen, the combination treatment reduced regulatory T cells and increased the proportion of CD8⁺ effector memory T cells. Collectively, current research demonstrates that separate delivery of CpG ODN and DOX through optimized nanocarriers effectively remodels the local TME and improves therapeutic efficacy. This dual-carrier strategy provides a practical approach for combining therapeutic agents with contrasting physicochemical properties in cancer chemo-immunotherapy.</div></div><div><h3>Statement of significance</h3><div>Cancer immunotherapy is often limited by an immunosuppressive tumor microenvironment (TME) that restricts effective immune activation. Chemo-immunotherapy combining CpG oligodeoxynucleotides (CpG ODN) with doxorubicin (DOX) may address this limitation by coupling dendritic cell (DC) maturation with immunogenic cell death in tumor. Here, we developed a dual-nanocarrier strategy in which CpG ODN and DOX were separately formulated in functionalized magnetic nanoparticles and metal–organic frameworks, respectively. This carrier-level separation enabled independent optimization of each therapeutic component while preserving their complementary functions within the tumor site. The combined treatment promoted DC maturation, remodeled the local TME, suppressed tumor growth, and prolonged survival in a murine breast cancer model. This work provides a practical method for combining physicochemically incompatible therapeutic agents in cancer chemo-immunotherapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 453-469"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802857","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":"Anterior cruciate ligament overuse increases collagen fibril compliance: collagen unraveling and elevated glycosaminoglycan activity in a murine model","authors":"Kevin H. Putera,&nbsp;Taeyong Ahn,&nbsp;Ben Loflin,&nbsp;Adam R. Carter,&nbsp;Roufael Hanna,&nbsp;Ameya Belamakar,&nbsp;Byron Cheatham,&nbsp;James A. Ashton-Miller,&nbsp;Edward M. Wojtys,&nbsp;Stephen H. Schlecht,&nbsp;Mark M. Banaszak Holl","doi":"10.1016/j.actbio.2026.08.035","DOIUrl":"10.1016/j.actbio.2026.08.035","url":null,"abstract":"<div><div>Data increasingly indicates that many anterior cruciate ligament (ACL) injuries are likely due to tissue damage accumulation and the gradual decrease in ACL strength and stiffness over time. Previous e<em>x vivo</em> experiments found molecular-level ACL damage (collagen unraveling) to be associated with increased tissue compliance at the collagen fibril-level. However, it remains unclear if this biomechanical effect is present <em>in vivo</em>, or what effect other modulators of tissue mechanics (<em>e.g.</em>, glycosaminoglycans (GAGs)) have in fatigued-damaged ACL matrices. Herein, we investigated the <em>in vivo</em> relationship between collagen unraveling and fibril-level mechanics in response to ACL fatigue loading in a mouse model and determined whether GAGs are also involved in altering tissue mechanics in this injury scenario. Mouse ACLs were submaximally fatigue loaded <em>in vivo</em> and harvested after one hour of tissue recovery. Compared to their contralateral controls, fatigued ACLs showed increased collagen unraveling and elevated GAG signatures within damaged extracellular matrix (ECM) regions. These regions also exhibited higher fibril-level compliance. Spectral data indicated colocalization of unraveled collagen and GAG-rich domains. Versican, a large aggregating PG, emerged as a candidate contributor to increased GAG presence in these regions. Together, these findings suggest that fatigue-induced collagen unraveling promotes local GAG accumulation – mediated by PGs such as versican – which likely contributes to reinforcement of the ECM.</div></div><div><h3>Statement of significance</h3><div>Outcomes from this anterior cruciate ligament (ACL) fatigue loading study provide high-resolution <em>in vivo</em> evidence for a structural and biochemical mechanism for the development of chronic overuse injuries. Our findings suggest that fatigue-induced tropocollagen unraveling increases collagen fibril-level tissue compliance, and that glycosaminoglycans rapidly colocalize with these damaged regions, further influencing ACL mechanics. The large aggregating proteoglycan, versican, was immunohistochemically identified as a candidate for glycosaminoglycan recruitment to the damaged extracellular matrix. Versican may be preferentially retained in domains of tropocollagen damage to facilitate the tissue remodeling response, though further research is needed to confirm this potential link.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"223 ","pages":"Pages 354-364"},"PeriodicalIF":10.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}