Acta Biomaterialia最新文献

{"title":"Dual-mechanism mucoadhesive hydrogel integrating pH-independent barriers and autophagy-driven immunotherapy for the treatment of ulcerative colitis","authors":"Jie Wang , Shenyuan Ouyang , Gaolong Lin , Dingwei Li , Bingyu Ding , Yumo Chen , Bingjie Tong , Ting Ouyang , Helin Xu , Wenzhi Wu","doi":"10.1016/j.actbio.2025.09.006","DOIUrl":"10.1016/j.actbio.2025.09.006","url":null,"abstract":"<div><div>Current therapies for ulcerative colitis (UC) face critical challenges, including systemic toxicity and inadequate mucosal regeneration. Herein, we present a pioneering dual-mechanism therapeutic platform integrating pH-independent acid-treated sucralfate (ASF) with autophagy-inducing spermidine (Spd) to synergistically address UC pathogenesis. Unlike conventional pH-dependent barrier therapies, ASF forms a mechanically tunable, injectable hydrogel that adheres robustly to colonic mucosa regardless of local pH. Spermidine was easily mounted into ASF hydrogel matrix via electrostatic interaction, with more than 90 % encapsulation efficiency. Moreover, the mechanical strength of ASF hydrogel was precisely modulated by adjusting spermidine amount in formula, making it suitable for effective gut mucosa coverage. Importantly, <em>in vitro</em> permeability test showed that spermidine-loaded ASF hydrogel (Spd-ASF) demonstrated the selective barrier functionality, blocking > 80 % of <em>Escherichia coli</em> and LPS penetration while allowing nutrient permeability. Moreover, micro-CT images demonstrated that rectally infused Spd-ASF hydrogel was uniformly adhered to the colon wall at least for 8 h. In DSS-induced colitis mice, rectally administrating Spd-ASF hydrogel uniquely restored colon length to near-normal levels (<em>vs.</em> 30 % shortening in controls), reduced proinflammatory cytokines (TNF-α, IL-6, IL-1β) by 60–75 %, and doubled goblet cell density. Mechanistically, Spd-ASF reprogrammed macrophage behavior by activating autophagy and enhancing efferocytosis, driving M2 polarization to resolve inflammation. Notably, Spd-ASF uniquely reversed dysbiosis, elevating beneficial <em>Lactobacillus</em> while suppressing colitis-associated <em>Muribaculaceae</em> and <em>Clostridia</em>. This study is the first to combine mucoadhesive biomaterial engineering with autophagy-mediated immunomodulation, offering a paradigm shift in UC therapy by simultaneously shielding the mucosa and reprogramming inflammatory pathways.</div></div><div><h3>Statement of significance</h3><div>Here, autophagy-inducing spermidine (Spd) and pH-independent acid-treated sucralfate (ASF) were combined to create the novel dual-mechanism hydrogel (Spd-ASF), which works in concert to combat UC pathogenesis. The selective barrier functioning of Spd-ASF hydrogel was established by its capacity to permit nutritional permeability while preventing the transfer of toxins (LPS) and pathogenic bacteria (<em>E. coli</em>). Additionally, rectally infused Spd-ASF hydrogel was consistently attached on the colon wall for at least eight hours, as seen by micro-CT images. Spd-ASF therapy doubled the density of goblet cells, decreased proinflammatory cytokines (TNF-α, IL-6, and IL-1β) by 60–75 %, boosted helpful <em>Lactobacillus</em>, and lowered pathogenic <em>Muribaculaceae</em> and <em>Clostridia</em>. It also restored colon length in DSS-induced colitis animals. Spd-ASF's therape","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"205 ","pages":"Pages 302-318"},"PeriodicalIF":9.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042393","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":"Smart wound management with sustainable pH sensing and dynamic electrotherapy","authors":"Zixin Zhu ,&nbsp;Laiyi Liu ,&nbsp;Qingyun Xie ,&nbsp;Song Chen ,&nbsp;Yiwan Sun ,&nbsp;Chenjun Huang ,&nbsp;Kyu-Jae Lee ,&nbsp;Xue Gou ,&nbsp;Xiaohong Li","doi":"10.1016/j.actbio.2025.08.033","DOIUrl":"10.1016/j.actbio.2025.08.033","url":null,"abstract":"<div><div>Smart wound management remains a significant challenge, necessitating real-time monitoring and dynamic treatment. Herein, an innovative multifunctional Janus dressing is designed to enable sustainable pH sensing, and provide dynamic drug delivery and electrical therapy at infected wounds. Specifically, the hydrophilic side is a pH-sensing layer with phenol red grafted onto amino-modified poly (2-hydroxyethyl methacrylate) via Mannich reaction, while the hydrophobic side contains drug-loaded piezoelectric particles semi-embedded in a polydimethylsiloxane matrix for therapeutic delivery. The dressing exhibits high flexibility (156 % elongation), strong water absorption (123 %), rapid pH sensing (∼1.5 min), and controllable piezoelectricity. Upon application, wound exudates are autonomously pumped through micropores to the hydrophilic layer, signaling infection, triggering drug release and “high electric field” treatment via external ultrasound, achieving an antibacterial treatment with a rate of up to 97.5 %. Following antimicrobial treatment, natural body movements and skin tension exert mechanical loading on the dressing, facilitating self-powered “low electric field” stimulation for tissue repair. The smart wound management effectively detects wound infection and delivers dynamic, adaptive electrotherapy, reducing inflammatory responses, accelerating collagen deposition, and enhancing tissue regeneration. This study presents a promising approach for advancing integrated wound dressings that unify diagnosis and therapy.</div></div><div><h3>Statement of significance</h3><div>A multifunctional Janus dressing was developed to benefit sustainable pH sensing, and enable drug delivery alongside dynamic electrotherapy. Upon application, wound exudate was automatically drawn through micropores into the hydrophilic layer, triggering the release of an infection signal that initiates drug release. Subsequently, antibacterial treatment was administered via a high electric field facilitated by external ultrasound. Following antibacterial therapy, a self-powered low electric field promoted tissue regeneration. The dressing exhibited 156 % elongation, 123 % water absorption, and a rapid pH response (∼1.5 min). Both <em>in vitro</em> and <em>in vivo</em> studies demonstrated that this strategy significantly accelerated wound healing, establishing a smart system for personalized wound management.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 354-370"},"PeriodicalIF":9.6,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982100","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":"Endothelial function-biomimetic hydrogel-surface engineered non-glutaraldehyde bioprosthetic valve with antithrombotic, immunomodulatory and pro-endothelialization performance","authors":"Lepeng Chen ,&nbsp;Fengyao Chi ,&nbsp;Xueyu Huang ,&nbsp;Bangquan Wei ,&nbsp;Li Yang ,&nbsp;Rifang Luo ,&nbsp;Cheng Zheng ,&nbsp;Yunbing Wang","doi":"10.1016/j.actbio.2025.08.022","DOIUrl":"10.1016/j.actbio.2025.08.022","url":null,"abstract":"<div><div>The progress of transcatheter valve replacement has significantly reduced the risk of valve replacement, increasing the demand for bioprosthetic heart valves (BHVs). Currently, the defects of BHVs, including thrombosis, poor endothelialization, calcification, and immune responses that are associated with glutaraldehyde crosslinking and their xenogeneic collagenous matrix, have accelerated the degeneration of BHVs. Herein, we constructed an endothelial function biomimetic hydrogel surface engineered non-glutaraldehyde BHV based on bioinspired catechol-crosslinking system and metal-chelation. An endothelial glycocalyx-like layer was anchored on BHV through the bioinspired oxidative coupling of catecholic porcine pericardium and alginate to mimic the endothelial glycocalyx on the inner wall of blood vessels, by which we also simultaneously achieved the crosslinking of BHV and the enrichment of bioactive catechols on BHV. Furthermore, the copper ions were introduced through chelation with alginate and catechol to impart glutathione peroxidase (GPx)-like functionality to BHVs, which mimicked the nitroxide (NO) generation performance of endothelium. The engineered BHV not only resisted the thrombosis, alleviated oxidative stress and modulated the immune responses but also facilitated the endothelialization. Moreover, the calcification of the BHVs was also significantly reduced in rat subcutaneous model. Altogether, this work presents significant potential to prolong the service life of BHVs.</div></div><div><h3>Statement of Significance</h3><div>Bioprosthetic heart valves (BHVs) are prone to degeneration due to thrombosis, poor endothelialization, calcification, and immune responses which are closely associated with the defects of glutaraldehyde crosslinking and their xenogeneic collagenous matrix. Based on catechol cross-linking and metal-phenol chemistry, we engineered a non-glutaraldehyde BHV with an endothelial function biomimetic hydrogel surface to prevent thrombosis, reduce calcification, and enhance endothelialization and immunomodulation. The endothelial function biomimetic hydrogel surface resists blood fouling and thrombosis, forming a catechol-rich entity to alleviate oxidative stress and modulate immune responses. The incorporation of copper ions confers GPx-like functionality, mimicking endothelial nitric oxide generation and facilitating the endothelialization. This work holds potential to extend the lifespan of BHVs and presents a promising candidate for the next generation of multi-functional BHVs.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 257-276"},"PeriodicalIF":9.6,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877212","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":"An immunocompetent bioengineered human dermal equivalent to recapitulate scar tissue formation in vitro","authors":"Roberta Passariello ,&nbsp;Giorgia Imparato ,&nbsp;Costantino Casale ,&nbsp;Francesco Urciuolo ,&nbsp;Paolo Antonio Netti","doi":"10.1016/j.actbio.2025.08.027","DOIUrl":"10.1016/j.actbio.2025.08.027","url":null,"abstract":"<div><div>Scar formation, a natural outcome of cutaneous repair, poses significant clinical challenges due to its aesthetic, functional, and psychological impacts. Existing experimental models, while enhancing our understanding of wound healing, often fail to capture the intricate cellular, molecular, and structural mechanisms underlying scar tissue formation. In this study, we present an advanced immunocompetent three-dimensional human dermal equivalent (3D-HDE) model that incorporates M2a macrophages to mimic inflammation and fibrosis <em>in vitro</em>. By inducing secondary intention wounds via punch biopsy and introducing M2a macrophages, the model successfully replicates key features of fibrotic tissue, including the overactivation of fibroblasts into myofibroblasts, aberrant extracellular matrix (ECM) production and dysfunctional ECM assembly. M2a macrophages were found to regulate the anomalous assembly of the ECM, driving the formation of densely packed and aligned collagen type I fibers, primarily by facilitating the transformation of fibroblasts into myofibroblasts. This innovative model provides a physiologically relevant platform for studying the dynamic interplay between macrophages, myofibroblasts, and ECM remodeling during scar evolution. The immunocompetent 3D-HDE model opens new avenues for investigating wound healing mechanisms, fibrosis and the development of targeted anti-fibrotic therapies.</div></div><div><h3>Statement of Significance</h3><div>Current in vitro tissue models often fail to capture the complexities of human fibrosis at both the cellular and extracellular levels. To address this, our study introduces an immunocompetent three-dimensional human dermal equivalent (3D-HDE) model, incorporating M2 macrophages to explore the role of immune cells in scar tissue formation. This innovative model effectively replicates key features of fibrosis, including fibroblast activation, extracellular matrix (ECM) deposition and remodeling, and collagen alignment. The physiological relevance of our model not only facilitates the study of fibrosis but also enables the testing of anti-fibrotic therapies, providing deeper insights into macrophage-driven wound healing mechanisms. This work bridges a critical gap between traditional in vitro models and clinical applications, advancing our understanding of wound healing, immune responses, and tissue engineering.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 293-311"},"PeriodicalIF":9.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877211","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":"Enamel-like stiffness achieved by poorly oriented nanocrystals in the capping tissue of Mexican beaded lizard osteoderms","authors":"Adrian Rodriguez-Palomo ,&nbsp;Malene Siri Berg Jacobsen ,&nbsp;Thorbjørn Erik Køppen Christensen ,&nbsp;Mads Ry Vogel Jørgensen ,&nbsp;Innokenty Kantor ,&nbsp;Gabriella Willan ,&nbsp;Anthony Herrel ,&nbsp;Arsalan Marghoub ,&nbsp;Mehran Moazen ,&nbsp;Susan Evans ,&nbsp;Matthew Vickaryous ,&nbsp;Catherine J.A. Williams ,&nbsp;Henrik Birkedal","doi":"10.1016/j.actbio.2025.08.025","DOIUrl":"10.1016/j.actbio.2025.08.025","url":null,"abstract":"<div><div>Osteoderms, skeletal structures in the skin, are found in many animals and serve diverse roles. In some lizards, the bony osteoderm has a capping tissue (<em>CT</em>) whose composition and structure remain unknown. Here, the composition and nanostructure of osteoderms from the Mexican beaded lizard (<em>Heloderma horridum</em>) are investigated. The <em>CT</em> is highly mineralized with an extraordinarily high elastic modulus. Within the osteoderm, a transition zone between capping and bone tissue forms a graded increase in mineralization towards the superficial <em>CT</em>. Unlike other examples of mineralized tissues, the <em>CT</em> demonstrates a new combination of physical properties and nanostructural organization. It displays stiffness and hardness similar to enamel, and hydroxyapatite crystals that are an order of magnitude larger than those within the bone tissue and are, thus, reminiscent of enamel crystals. However, in stark contrast to enamel, the <em>CT</em> displays only minimal preferred orientation of the crystallites. Thus, it achieves very high mechanical properties with enamel-like crystal sizes but with near-isotropic microstructural orientation. The Mexican beaded lizard <em>CT</em> presents a highly unusual structural design resulting in high-performance mechanics.</div></div><div><h3>Statement of Significance</h3><div>The stiffest tissue in vertebrates is enamel, which is characterized by large, highly oriented nanocrystals. The less stiff bone has smaller nanocrystals and a lower, but still high degree of texture. The osteoderms of the Mexican beaded lizard are herein investigated by a combination of mechanical testing, spatially resolved X-ray diffraction and fluorescence, and 3D X-ray imaging. Surprisingly, the osteoderms have a capping tissue with enamel-like stiffness, significantly larger crystals than the underlying bone but are much less textured. This provides a new type of design for hard biological tissues.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 457-469"},"PeriodicalIF":9.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862690","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":"Localized growth factor delivery from microparticles modulates osteogenic and chondrogenic gene expression in a growth factor-dependent manner in an ex vivo chick embryonic bone model","authors":"Hassan Rashidi ,&nbsp;Helen C. Cox ,&nbsp;Omar Qutachi ,&nbsp;Dale Moulding ,&nbsp;Lisa J. White ,&nbsp;Emma L. Smith ,&nbsp;Janos M. Kanczler ,&nbsp;Luis Rojo ,&nbsp;Michael Rotherham ,&nbsp;James R. Henstock ,&nbsp;Molly M. Stevens ,&nbsp;Alicia J. El Haj ,&nbsp;Richard O.C. Oreffo ,&nbsp;Kevin M. Shakesheff ,&nbsp;Felicity R.A.J. Rose","doi":"10.1016/j.actbio.2025.08.028","DOIUrl":"10.1016/j.actbio.2025.08.028","url":null,"abstract":"<div><div>Growth factors play a crucial role in regulating various cellular functions, including proliferation and differentiation. Consequently, the biomaterial-based delivery of exogenous growth factors presents a promising strategy in regenerative medicine to manage the healing process and restore tissue function. For effective therapeutic applications, it is essential that these active compounds are precisely targeted to the site of regeneration, with release kinetics that align with the gradual pace of tissue growth. We have developed an ex vivo model utilizing a developing embryonic chick bone, and using PLGA-based microparticles as controlled-release systems, allowing for the investigation of the spatiotemporal effects of growth factor delivery on cell differentiation and tissue formation. Our findings demonstrate that BMP2 and FGF2 can significantly alter cell morphology and zonally pattern collagen deposition within the model, but only when the growth factor presentation rate is carefully regulated. Furthermore, the growth factor-dependent responses observed underscore the potential of this model to explore interactions between cells and the growth factors released from biomaterials in an approach which can be applied to bone tissue engineering.</div></div><div><h3>Statement of significance</h3><div>Current biomaterial-based strategies for bone tissue engineering face critical limitations in mimicking the spatial and temporal dynamics of native tissue development. This study introduces an innovative ex vivo embryonic chick bone model to evaluate localized, sustained growth factor delivery using PLGA microparticles. By precisely controlling the release of BMP2 and FGF2, the research demonstrates growth factor-specific modulation of osteogenic and chondrogenic gene expression and matrix deposition, outcomes that traditional in vitro models fail to capture. This physiologically relevant platform bridges a critical gap between basic in vitro assays and complex in vivo models, offering a powerful, low-cost tool for preclinical screening of regenerative therapies, and advancing the rational design of next-generation bone healing strategies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 558-567"},"PeriodicalIF":9.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859977","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-reinforceable poly(lipoic acid)-based tough underwater tissue bioadhesive","authors":"Xiaoyu Yang ,&nbsp;Miaomiao Jiang ,&nbsp;Zongxuan Huang ,&nbsp;Hongjian Huang ,&nbsp;Hu Zhao ,&nbsp;Qinhui Chen ,&nbsp;Haiqing Liu","doi":"10.1016/j.actbio.2025.08.024","DOIUrl":"10.1016/j.actbio.2025.08.024","url":null,"abstract":"<div><div>Strong and durable adhesion of bioadhesives on wet/underwater tissues is still challenging because of the hindrance of the hydration layer and swelling of the adhesive. Here a water-induced self-hardening bioadhesive (p(LA-ABO)) composed of poly(lipoic acid) (PolyLA) capped with 4-allyl-1,2-benzenediol (ABO), is prepared through a solvent evaporation-induced self-polymerization method. During underwater curing, the water-induced aggregation of the hydrophobic PolyLA chain of the bioadhesive leads to a soft-to-hard transition, therefore enhancing its cohesion and wet/underwater tissue adhesion. Its tensile strength and adhesion strength on wet porcine skin respectively increased from 57.77 kPa to 93.87 kPa and from 50.48 kPa to 80.59 kPa in 6 h wet adhesion. Moreover, it can still maintain robust adhesion without weakening (∼85.09 kPa) after 6 h of underwater adhesion. Additionally, the adhesive exhibits a very low swelling (∼1.1%) after 12 h of water immersion. It also shows on-demand detachment, good biocompatibility, and biodegradability. By sandwiching a conductive fabric between two bioadhesives, a strain sensor with a high conductivity is created for sensing body motion signals. This integration of water-induced self-hardening wet adhesion with sensing performance may open a new avenue in the design of biosensors for wet/underwater applications.</div></div><div><h3>Statement of significance</h3><div>Bioadhesives have gained growing attention owing to their wide industrial and biomedical applications. However, despite significant efforts, it remains challenging to achieve strong, stable, and durable wet/underwater adhesion in a simple and effective manner due to an interfacial water barrier. To address this issue, we engineer a water-induced self-hardening PolyLA-based bioadhesive with durable and robust wet/underwater adhesion. Furthermore, by integrating this bioadhesive with conductive cotton fabrics, a highly sensitive and rapidly response to body motion signals strain sensor was created, expanding its application range in wet environments. Therefore, this research offers a new methodology for developing wet/underwater biosensors.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 371-385"},"PeriodicalIF":9.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857155","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":"Cellular changes in an in vitro neural circuit system under simulated microgravity","authors":"Dahee Ryu ,&nbsp;Dohyung Kim ,&nbsp;Yoonhee Shim ,&nbsp;Geonho Jin ,&nbsp;Seonghun Mun ,&nbsp;Jinsik Kim ,&nbsp;Hyeon-Seung Yoon ,&nbsp;Steve K. Cho ,&nbsp;Hansung Kim ,&nbsp;Jeong-Seok Choi ,&nbsp;Hye Jin Yoo ,&nbsp;Seokyoung Bang ,&nbsp;Su-Geun Yang","doi":"10.1016/j.actbio.2025.08.023","DOIUrl":"10.1016/j.actbio.2025.08.023","url":null,"abstract":"<div><div>Physiological changes, some of which lead to neurological alterations and cognitive decline, have been reported to occur in space. To date, it has not been possible to identify the direct effect of microgravity alone on neural circuits <em>in vitro</em>. Therefore, this study aimed to elucidate the impact of simulated microgravity (sμG) on neural circuit dynamics using a microphysiological system (MPS). A unidirectional neural circuit MPS was engineered, and primary neurons from embryonic day 17 (E17) rat brains were extracted, seeded onto the system, and maintained under terrestrial conditions for two weeks to establish functional connectivity. Subsequently, cultures were exposed to either ground conditions or sμG using a rotating clinostat for an additional week. Neurons subjected to sμG exhibited a significant increase in oxidative stress and spontaneous Ca²⁺ activity, accompanied by a marked reduction in axonal density and synapsin-1 expression. Notably, sμG did not affect neuronal viability. Finally, transcriptomic analysis further revealed significant alterations in <em>HSPA4</em> and <em>SNCA</em> expression, genes implicated in cellular stress responses and neurodegenerative pathology. This study represents the first practical application of a neural circuit MPS for physiological research. These findings underscore the utility of neural circuit MPSs as robust platforms for modeling the neurobiological consequences of microgravity and evaluating countermeasures to mitigate neural dysfunction in long-duration spaceflight.</div></div><div><h3>Statement of Significance</h3><div>Long-term exposure to space environments, including microgravity and cosmic radiation, induces physiological changes, some leading to neurological impairments. However, the direct effects of microgravity on neural circuits remain unclear. Using a system that isolates microgravity, we demonstrate increased ROS generation, inhibited axon growth, altered synapse formation, and gene expression changes linked to neurodegenerative diseases. These findings highlight the potential risks of microgravity on neural function. MPS technologies, such as neural circuits on chips, are essential for space medicine and can provide platforms for drug testing to prevent space-induced cognitive decline. We anticipate that our technology will pave the way for examining the interaction between space environments and brain tissue at the cellular level in a practical and multifaceted manner.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 446-456"},"PeriodicalIF":9.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857152","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":"Chlorocatechol-functionalized gelatin nanoparticles as a hemostatic agent with antimicrobial properties","authors":"Fatemeh Razaviamri,&nbsp;James Manuel,&nbsp;Kan Wang,&nbsp;Zhongtian Zhang,&nbsp;Bruce P. Lee","doi":"10.1016/j.actbio.2025.08.020","DOIUrl":"10.1016/j.actbio.2025.08.020","url":null,"abstract":"<div><div>Hemorrhage is one of the leading preventable causes of death associated with trauma, which is often complicated by wound infection. Current hemostatic materials are not ideal and lack antimicrobial properties needed for infection prevention. Here, we tested the feasibility for 6-chlorodopamine-functionalized gelatin (GDC) nanoparticles to function as a hemostatic powder with strong tissue adhesion and antibacterial properties. 6-Chlorodopamine contains a catechol sidechain that is further modified with an electron withdrawing chlorine atom, and provides strong tissue adhesion and antimicrobial property. These gelatin nanoparticles are not covalently crosslinked, which enablde them to rapidly transition into an adhesive film when hydrated with an aqueous solution or blood. The chlorination of catechol significantly increased structural integrity, interfacial bonding to tissue surface, and the rate of film formation. Additionally, GDC nanoparticles are noncytotoxic and nonhemolytic, and effectively killed Gram-positive (<em>Staphylococcus epidermidis, Staphylococcus aureus</em>) and Gram-negative (<em>Escherichia coli</em>) bacteria. Finally, GDC nanoparticles achieved significantly faster hemostasis and reduced blood loss when compared to a commercial fibrin glue, Tisseel, in tail transection and liver hemorrhage models performed in mice. These findings highlight the potential of GDC nanoparticle as a versatile, multifunctional hemostatic agent capable of both rapid hemorrhage control and infection prevention.</div></div><div><h3>Statement of Significance</h3><div>Existing hemostatic agents often lack effective antimicrobial properties and may not be suited for application in a prehospital setting. This work evaluated a multifunctional, hemostatic nanoparticle that addresses key challenges in hemorrhage control and infection prevention, through a simple, bioinspired formulation. Gelatin nanoparticles were functionalized with chlorocatechol (GDC) that can rapidly transition into adhesive films when hydrated with blood. Chlorocatechol imparted the nanoparticles with strong tissue adhesion, film integrity, and antimicrobial property. In mouse hemorrhage models, GDC significantly reduced blood loss and bleeding time when compared to a commercial fibrin sealant. This powder-form material requires no mixing or specialized equipment to deploy, which makes it potentially suitable for application in a prehospital setting.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 568-581"},"PeriodicalIF":9.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857153","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":"MIL-100(Fe)-based Co-delivery platform as cascade synergistic chemotherapy and immunotherapy agents for colorectal cancer via the cGAS-STING pathway","authors":"Pai Wang ,&nbsp;Heshi Liu ,&nbsp;Lei Guo ,&nbsp;Yixin Tang ,&nbsp;Tianwei Lan ,&nbsp;Rui Zhou ,&nbsp;Huiqing Xu ,&nbsp;Lu Wang ,&nbsp;Xue Wang ,&nbsp;Baiqiao Chen ,&nbsp;Yixing Wang ,&nbsp;Siyuan Wang ,&nbsp;Chang Liu ,&nbsp;Jie Chen ,&nbsp;Caina Xu ,&nbsp;Quan Wang ,&nbsp;Huayu Tian","doi":"10.1016/j.actbio.2025.08.021","DOIUrl":"10.1016/j.actbio.2025.08.021","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Colorectal cancer (CRC) remains a major global health burden as the third most commonly diagnosed malignancy and the second leading cause of cancer-related mortality worldwide. While combination chemotherapy and immune agonists hold potential to overcome tumor heterogeneity through multi-pathway modulation, their therapeutic efficacy remains limited by off-target drug distribution and immunosuppressive tumor microenvironment (TME). To address this, we developed a tumor-targeted chemo-immunotherapy platform by encapsulating irinotecan (CPT-11) and resiquimod (R848) in hyaluronic acid (HA) coated MIL-100(Fe) metal-organic frameworks (CRMH NPs), enabling CD44-mediated delivery and synergistic anti-tumor responses. The system enabled controlled drug release in the acidic TME, promoting immunogenic cell death (ICD), inducing the cGAS-STING pathway and activating immune cells. &lt;em&gt;In vitro&lt;/em&gt;, CRMH NPs induced significant ICD, as evidenced by the release of damage-associated molecular patterns (DAMPs) like high mobility group box 1 (HMGB1) and calreticulin (CRT), and matured dendritic cells (DCs), which triggered by TLR7 agonist, enhancing immune responses. It also activated the cGAS-STING pathway, which could efficiently induce the targeted cells to produce type I interferon (IFN) and proinflammatory cytokines, thereby enhancing T cell activation and recruitment. &lt;em&gt;In vivo&lt;/em&gt;, CRMH NPs significantly reduced tumor growth in CT26 mouse models, activated innate immune signaling, and increased immune cell infiltration, demonstrating superior anti-tumor effects compared to free drugs and other nanoparticle formulations. Furthermore, CRMH NPs upregulated PD-L1 expression on tumor cells, suggesting potential synergy with immune checkpoint blockade therapy. Combining CRMH NPs with anti-PD-L1 therapy enhanced anti-tumor immunity, particularly in distant tumors, highlighting a promising approach to overcoming immune evasion and achieving durable tumor regression. These findings supported CRMH NPs as a versatile and effective platform for chemo-immunotherapy in CRC.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Statement of Significance&lt;/h3&gt;&lt;div&gt;Colorectal cancer (CRC) remains a major global health challenge with limited treatment efficacy due to tumor heterogeneity and immunosuppression. This study introduces a novel tumor-targeted nanoparticle platform, CRMH NPs, which co-deliver the chemotherapeutic drug irinotecan (CPT-11) and the immune agonist resiquimod (R848) using hyaluronic acid-coated MIL-100(Fe) metal-organic frameworks. CRMH NPs enhance drug delivery, induce immunogenic cell death, and activate the cGAS-STING pathway, synergizing chemotherapy and immunotherapy. Demonstrating superior tumor suppression and immune activation in preclinical models, this platform overcomes key limitations of current therapies, such as off-target effects and immune evasion. Its combination with anti-PD-L1 therapy further improves outcomes, offering a promising strategy for durable","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"204 ","pages":"Pages 582-595"},"PeriodicalIF":9.6,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857154","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}