{"title":"Biofilm-triggered interfacial assembly of dual-porphyrin heterojunctions for chemo-/sonodynamic treatment of pyomyositis.","authors":"Junwu Wei, Tian Xia, Jing Xia, Tianyu Gao, Guiyuan Zhang, Peng Huang, Xiaohong Li","doi":"10.1016/j.actbio.2025.07.069","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.07.069","url":null,"abstract":"<p><p>Sonodynamic therapy (SDT) indicates advantages in combating antibiotics-resistant bacteria and deep tissue infections, but challenges remain in the development of highly efficient, infection-responsive, and biocompatible sonosensitizers. Herein, tetrakis (4-hydroxyphenyl) porphyrin (TH) and tetrakis (4-carboxyphenyl) zinc porphyrin (ZnTC) are proposed to construct dual-porphyrin heterojunctions (TH/ZnTC), and their matched interface and strong interfacial electric field (IEF) enhance charge density and transfer for selective and efficient SDT. Specifically, metal organic frameworks were constructed through coordination of Fe<sup>3+</sup> and ZnTC and simultaneously loading TH to prepare TH@FeM. In infection sites with elevated glutathione, Fe³⁺ is reduced to Fe²⁺, triggering TH@FeM decomposition and TH/ZnTC self-assembly through π-π stacking and electrostatic interactions. IEF from ZnTC to TH drives the formation of S-scheme TH/ZnTC heterojunctions and greatly promotes efficient separation and transfer of the generated charges at the matched interface for efficient generation of reactive oxygen species. Meanwhile, GSH-reductive releases of Fe<sup>2+</sup> enable high Fenton reaction activity for chemodynamic therapy. After intravenous injection into a mouse pyomyositis model, the enhanced penetration and retention in the infected muscles implements up to 3.1-folds higher fluorescence intensities than those of the major tissues. Ultrasonication of TH@FeM fully destructs bacteria, downregulates inflammatory factor levels, promotes angiogenesis, and accelerates healing of infected muscles without significant pathological and functional changes in the main organs, leading to continuous decreases in clinical scores and full survival of pyomyositis mice. Thus, the concise design represents the first attempt to explore biofilm-responsive heterojunction formation for synergistic chemo-/sonodynamic therapies of bacterial infections. STATEMENT OF SIGNIFICANCE: Nearly 80% of chronic infections are linked to biofilm formation on living tissues. Extracellular polysaccharides produced by biofilms confer protection, making bacteria 10-1000 times more resistant to antibiotics compared to their planktonic counterparts, thus complicating treatment. Sonodynamic therapy (SDT) offers promising advantages in addressing antibiotics-resistant bacteria and deep tissue infections, but challenges remain in the development of highly efficient, infection-responsive, and biocompatible sonosensitizers. Herein, we propose biofilm-responsive generation of dual-porphyrin heterojunctions with matched interface and strong interfacial electric field, which enhance charge density and transfer for selective and efficient SDT. The glutathione-responsive formation and charge transfer mechanisms were both theoretically calculated and experimentally validated. Furthermore, target accumulation and treatment efficacy were demonstrated in a pyomyositis model.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta biomaterialiaPub Date : 2025-07-31DOI: 10.1016/j.actbio.2025.07.068
Yangeng Wang, Wenzhe Xuan, Chengqiong Mao, Yang Liu
{"title":"Inhalable Nucleic Acid Therapeutics for Chronic Pulmonary Disease: Progress, Challenges, and Prospects.","authors":"Yangeng Wang, Wenzhe Xuan, Chengqiong Mao, Yang Liu","doi":"10.1016/j.actbio.2025.07.068","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.07.068","url":null,"abstract":"<p><p>Inhalable nucleic acid drug delivery systems have garnered increasing attention as a promising strategy for the treatment of chronic pulmonary diseases, such as asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and idiopathic pulmonary fibrosis (IPF). These diseases are often characterized by chronic inflammation, airway remodeling, and progressive lung dysfunction, posing significant clinical challenges. Nucleic acid therapeutics, including plasmid DNA, messenger RNA (mRNA), microRNA (miRNA), small interfering RNAs (siRNAs), and antisense oligonucleotides (ASOs), offer the potential to correct genetic defects, modulate aberrant gene expression, or suppress pathogenic signaling pathways. The inhalation route enables direct, non-invasive access to the lungs, offering localized delivery, rapid onset of action, and reduced systemic side effects. However, the lung presents multiple biological barriers that limit the delivery and activity of nucleic acids, including mucus clearance, enzymatic degradation, alveolar macrophage uptake, and cellular membrane penetration. To address these challenges, various delivery vectors-ranging from viral vectors to non-viral systems such as lipid nanoparticles, polymeric carriers, and hybrid nanomaterials-have been engineered to enhance stability, targeting, and transfection efficiency. This review highlights recent advances in inhalable nucleic acid delivery platforms, discusses the critical physiological and pathological barriers in the pulmonary microenvironment, and outlines current clinical progress. Finally, we explore future directions and challenges toward clinical translation of these innovative therapies. STATEMENT OF SIGNIFICANCE: Chronic pulmonary diseases, including COPD, asthma, IPF, and CF, remain among the leading causes of morbidity and mortality worldwide, with limited treatment options that target disease pathogenesis at the molecular level. Nucleic acid therapeutics offer transformative potential to precisely regulate gene expression, correct mutations, and modulate inflammatory or fibrotic pathways. However, effective delivery to the lungs remains a critical barrier to clinical translation. This review highlights the emerging field of inhalable nucleic acid delivery systems, integrating recent advances in nanocarrier design, pulmonary targeting strategies, and the navigation of biological barriers. By bridging nucleic acid pharmacology with pulmonary drug delivery science, this review provides a comprehensive framework for the rational design and clinical development of next-generation genetic therapies for respiratory diseases. It also offers forward-looking perspectives on overcoming current translational hurdles, thereby accelerating the realization of precision gene therapy for chronic lung disorders.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta biomaterialiaPub Date : 2025-07-31DOI: 10.1016/j.actbio.2025.07.038
Carla Nathaly Villacís Núñez, Ulrich Scheven, Asheesh Bedi, Ellen M Arruda
{"title":"Tear growth mechanisms in high-grade bursal-sided partial thickness tears in the rotator cuff measured with full volume magnetic resonance imaging methods.","authors":"Carla Nathaly Villacís Núñez, Ulrich Scheven, Asheesh Bedi, Ellen M Arruda","doi":"10.1016/j.actbio.2025.07.038","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.07.038","url":null,"abstract":"<p><p>In this work, we evaluate the mechanical response of rotator cuff tendons with high-grade partial thickness tears through a recently developed full volume measurement technique that resolves through-thickness behavior. As opposed to traditional strain measurement methods, which examine surfaces of the tendon or localized two-dimensional regions, we have probed three-dimensional strains including internal locations via magnetic resonance imaging. Differences between the intact and torn states have been considered in an ex-vivo ovine model of the rotator cuff. The torn condition depicts sliding between cut/uncut tissue regions, with high shear strain concentrations at the boundaries of detached/attached tissue portions. At both submaximal and supramaximal force levels, the internal and inferior bands of the tendon show high shear strain magnitudes, which could indicate regions of high risk for tear propagation. Geometrical features which could explain strain distribution differences in their intact and torn conditions are also analyzed. Through the understanding of full volume displacement and strain distributions, our study elucidates why two-dimensional values might not represent the global behavior of the injured tendon, critical components of the Lagrangian strain tensor which have not been probed before, and important implications for surgical repairs.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144769437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta biomaterialiaPub Date : 2025-07-30DOI: 10.1016/j.actbio.2025.07.043
Franziska S Egli, Seyed Morteza Seyedpour, Mohammad Pachenari, David M Pierce, Tim Ricken
{"title":"Computational modeling of articular cartilage: Mechanical experiments, sensitivity analyses, parameter identification, and validation.","authors":"Franziska S Egli, Seyed Morteza Seyedpour, Mohammad Pachenari, David M Pierce, Tim Ricken","doi":"10.1016/j.actbio.2025.07.043","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.07.043","url":null,"abstract":"<p><p>Articular cartilage is a complex, multiphase material whose mechanical behavior is crucial for understanding joint function and diseases such as osteoarthritis. In this study we address the critical need to improve the fidelity of finite element simulations for cartilage by integrating mechanical experiments, sensitivity analyses, parameter identification, and validation to refine a well-established biphasic constitutive model for articular cartilage. Our sensitivity analyses using the Morris method identified fiber stiffness as dominant in uniaxial extension, while permeability and matrix stiffness played significant roles in confined compression. Parameter fitting for uniaxial extension achieved an excellent match with experimental force-displacement curves (R<sup>2</sup>≥0.989), and fitting permeability parameters for confined compression achieved a similarly excellent match to stress-strain responses (R<sup>2</sup>>0.998). Independent validation against biaxial extension experiments demonstrated that simulated stress-strain curves fell within the experimental range. Displacement and strain fields from uniaxial extension simulations also showed good agreement with data from digital image correlation, with minor discrepancies attributed to experimental variability and boundary conditions. Our results underscore the importance of fiber reinforcement in tension and interstitial fluid pressurization in compression. We publicly release our work via the data repository of the University of Stuttgart (DaRUS, https://doi.org/10.18419/DARUS-4729). Our validated biphasic model provides a robust tool for investigating cartilage mechanics and could aid in developing improved treatments for cartilage degeneration. Statement of Significance Articular cartilage is an anisotropic, heterogeneous soft tissue facilitating frictionless function of joints. Its complex microstructure determines the load-bearing functionality, and varies among patients and in disease. We advance understanding of cartilage mechanics by employing a specialized, biphasic constitutive model implemented within FEBio (University of Utah) to analyze cartilage under diverse loading conditions. We conduct sensitivity analyses leveraging new experiment data from uniaxial tension and confined compression testing to establish key material parameters and assess the model's sensitivity. Experimental data from uniaxial tension, confined compression, and biaxial tension provide additional insights into the heterogeneous mechanical behavior of this remarkable soft tissue. By combining new experiments, sensitivity analyses, and careful parameter fittings, we validated our fitted model and improved prediction fidelity.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta biomaterialiaPub Date : 2025-07-30DOI: 10.1016/j.actbio.2025.07.064
Juanyong Li, Chaokai Zhang, Habibeh Ashouri, Jiazhang Chen, Taylor Paradis, Bryanna Samolyk, Owen Beaver, George Pins, Qi Wen, Nima Rahbar, Songbai Ji, Kristen Billiar
{"title":"Toroidal Indentation for Measuring Cell and Tissue Mechanical Anisotropy.","authors":"Juanyong Li, Chaokai Zhang, Habibeh Ashouri, Jiazhang Chen, Taylor Paradis, Bryanna Samolyk, Owen Beaver, George Pins, Qi Wen, Nima Rahbar, Songbai Ji, Kristen Billiar","doi":"10.1016/j.actbio.2025.07.064","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.07.064","url":null,"abstract":"<p><p>Indentation-based mechanical tests are advantageous for measuring tissue and cell stiffness due to their simplicity and ability to probe samples non-destructively. Most commonly, spherical or pyramidal probes are used, and Hertzian analysis is applied to calculate the modulus. This technique assumes material isotropy which ignores the direction-dependent properties of fibrous tissues and polarized cells. In this study, we aimed to develop a generalized indentation method to estimate the anisotropic elastic moduli of biomaterials across scales from macroscopic tissues to single cells. Torus-shaped indenter probes were created with radii ranging from millimeters to microns and aspect ratios up to 10:1. Anisotropic muscle tissue, cell monolayers, and single cells were indented in directions perpendicular and parallel to their preferred fiber orientations. To determine intrinsic anisotropic moduli (E<sub>1</sub> and E<sub>2</sub>), a linear incompressible transversely isotropic material model was developed, and finite element modeling was used to simulate normalized loading curve pairs for a wide range of E<sub>1</sub>:E<sub>2</sub> parameter sets. A deep learning model was then trained with the simulated data and used to calculate the moduli. We found that the degree of anisotropy (E<sub>1</sub>:E<sub>2</sub>) was comparable to published results for muscle (∼1:3.7), aligned cell monolayers (∼1:3.6), and polarized single cells (∼1:1.7). This method generalizes the isotropic Hertzian indentation approach for anisotropic biomaterials and cells across length scales. The toroidal probes can be fabricated for less than $30 and are compatible with commercial indenters, making the method widely accessible to researchers. STATEMENT OF SIGNIFICANCE: The toroidal indentation method and the finite element based deep learning model developed in this study provides a readily available, accessible, and low-cost method to measure anisotropic stiffness of broad biological materials from macroscopic tissues to microscopic cells using conventional laboratory devices, which was, to the best of our knowledge, impossible without using imaging and inverse finite element model or highly specialized customized equipment. By providing a tool, This study has the potential to facilitate the understanding of mechanical properties of anisotropic biological systems such as polarized cells, multicellular aggregates, and micro tissues, hence expedite the studies in tissue engineering, biomechanics, and mechanobiology.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta biomaterialiaPub Date : 2025-07-29DOI: 10.1016/j.actbio.2025.07.063
Claudia A Garrido, Daniela S Garske, Christian H Bucher, Shahrouz Amini, Georg N Duda, Katharina Schmidt-Bleek, Amaia Cipitria
{"title":"Anisotropic Hydrogel Degradation Enhances 3D Collective Mesenchymal Stromal Cell Alignment, Mechanotransduction and Osteogenic Differentiation.","authors":"Claudia A Garrido, Daniela S Garske, Christian H Bucher, Shahrouz Amini, Georg N Duda, Katharina Schmidt-Bleek, Amaia Cipitria","doi":"10.1016/j.actbio.2025.07.063","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.07.063","url":null,"abstract":"<p><p>Tissue engineering involves assembling cells and mimicking the complex anisotropic architecture of biological tissues to perform specific functions. This study uses 3D alginate-based hydrogels with RGD binding motifs to explore the impact of anisotropic degradation of patterned hydrogels (two components: degradable (Deg) and non-degradable (noDeg)) compared to single-phase materials (one component: Deg or noDeg), on the potential of enhancing cell spreading, collective alignment, mechanotransduction and osteogenic differentiation of encapsulated human mesenchymal stromal cells (hMSCs). Spatial patterns of Deg and noDeg subregions are formed by photolithography: UV-triggered thiol-ene crosslinking with matrix metalloprotease (MMP) sensitive peptides form Deg phases, while non-UV exposed regions result in Diels-Alder spontaneous click crosslinking and noDeg phases. 3D patterns in hydrogel degradation enhance hMSC spreading and allow collective cell alignment in Deg areas, while cells remain rounded with no alignment in noDeg regions. In addition, we observe a boosted osteogenic differentiation when compared to single-phase materials, as mid osteogenic markers (osteocalcin) are expressed at day 14 in anisotropic gels, whereas in single-phase only early osteogenic markers are found (osterix). Mechanosensing pathways were evaluated using the expression and localization of YAP. Deg sections in patterned materials have an enhanced nuclear translocation and higher YAP expression compared to single-phase Deg materials and noDeg sections. This effect is lost and no patterns in YAP expression and localization emerge when using an MMP-scramble peptide or no-RGD materials. These findings demonstrate that 3D patterns in alginate hydrogel degradation guide hMSC spreading, collective alignment, enhance YAP nuclear translocation and osteogenic differentiation. Mimicking tissue anisotropy in 3D patterned hydrogels could have broad applications in biofabrication and tissue engineering. STATEMENT OF SIGNIFICANCE: Patterned materials integrate multiple characteristics within a single material, closely mimicking the anisotropy found in tissues. This research goes further by demonstrating how anisotropic degradation of cell-laden hydrogels leads to emerging patterns in mechanics. As a consequence, anisotropic hMSC morphology and collective alignment are observed in 3D patterned materials compared to single-phase counterparts. Additionally, we show enhanced and spatially guided hMSC osteogenic differentiation in patterned materials. Furthermore, anisotropic mechanosensing via YAP/TAZ signaling is shown to mediate this enhanced and spatially guided mechanotransduction and osteogenic differentiation. Finally, we explore how additional biochemical stimuli can further boost the spatially guided hMSC osteogenic differentiation. These findings advance our understanding of cell response in anisotropic microenvironments, with broad applications in biofabrication and tissu","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta biomaterialiaPub Date : 2025-07-29DOI: 10.1016/j.actbio.2025.07.031
Ying He, Zhaoxu Huang, Jie Liang, Hao Ji, Zhaoxia Pu
{"title":"Synergistic effects of biomaterials and extracellular vesicles in treating myocardial infarction: A systematic review of preclinical studies.","authors":"Ying He, Zhaoxu Huang, Jie Liang, Hao Ji, Zhaoxia Pu","doi":"10.1016/j.actbio.2025.07.031","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.07.031","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) combined with biomaterials have shown promise in treating myocardial infarction (MI), with potential to alleviate inflammation, oxidative stress, and apoptosis while improving cardiac function. However, systematic evaluation is needed. This meta-analysis utilized data from PubMed, Web of Science, Scopus, EMBASE, and Ovid medicine from their inception to May 2025. Relevant outcomes were analyzed using GetData Graph Digitizer 2.26 and Review Manager 5.4 software. The quality of studies was assessed using the SYRCLE risk of bias tool and CAMARADES checklist. We measured 12 indicators across cardiac function, fibrosis, apoptosis, and inflammation. The meta-analysis included 33 studies. Compared to EV monotherapy, the combination of EVs with biomaterials significantly improved several cardiac functions and structural parameters. These include: Ejection Fraction (SMD = 1.79; p < 0.00001); Fractional Shortening (SMD = 1.61; p < 0.00001); Myocardial Fibrosis (SMD = -1.83; p = 0.002); Additionally, IL-6 (SMD = -2.55; p = 0.01) and TNF-α (SMD = -1.18; p = 0.01), as well as apoptosis levels (SMD = -3.72; p < 0.0001), were markedly reduced. Among them, intramyocardial injection of MSC-derived EVs combined with hydrogel is the most widely used combination therapy. EVs combined with biomaterials enhance cardiac recovery in MI models with no significant safety issues, highlighting their potential therapeutic benefits. STATEMENT OF SIGNIFICANCE: Myocardial infarction (MI) is one of the leading causes of death and disease burden. Over the past 20 years, extracellular vesicles (EVs) have undergone a remarkable journey and are now poised on the brink of becoming the next generation of cell-free therapeutic tools. Our study aims to quantitatively analyze the efficacy and safety of combining biomaterials with EVs compared to EVs alone in MI through a meta-analytical mapping approach. This is the first comprehensive meta-analysis summarizing the effectiveness and safety of various biomaterials combined with EV therapy, highlighting the role of biomaterials in advancing the field. It provides valuable insights for researchers exploring the clinical translation of EV-based therapies.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta biomaterialiaPub Date : 2025-07-28DOI: 10.1016/j.actbio.2025.07.061
Bryan M Gregorits, Yi Wu, Chen Chen, Eric Yeager, Myddelton C Parker, Isabel Martinez, Meghan L Lancaster, Chad Schmiedt, Hitesh Handa, Harry R Allcock, Christopher A Siedlecki, Li-Chong Xu
{"title":"In Vitro and In Vivo Biocompatibility Study of Fluorinated Polyphosphazene Coatings for Blood-Contacting Medical Devices.","authors":"Bryan M Gregorits, Yi Wu, Chen Chen, Eric Yeager, Myddelton C Parker, Isabel Martinez, Meghan L Lancaster, Chad Schmiedt, Hitesh Handa, Harry R Allcock, Christopher A Siedlecki, Li-Chong Xu","doi":"10.1016/j.actbio.2025.07.061","DOIUrl":"https://doi.org/10.1016/j.actbio.2025.07.061","url":null,"abstract":"<p><p>Implant-induced thromboembolic events are the most common complication of blood contacting medical devices. Coatings are a promising approach to improve the biocompatibility of current biomaterials and devices. Poly[bis(trifluoroethoxy) phosphazene] (TFE) has been demonstrated to be biocompatible, anti-inflammatory, and antithrombogenic as a device coating over the past decades; however, its inherently poor mechanical properties make applications in medical devices challenging, especially regarding potential detachment from devices. Our previous work developed a new fluorinated polyphosphazene, poly[bis(octafluoropentoxy) phosphazene] (OFP), and incorporated allylphenoxy side groups to the P-N backbone to make the polymer crosslinkable (X-OFP). In this study, we applied this X-OFP coating on central venous catheters and investigated the surface properties and biocompatibility of the coatings. In vitro and in vivo studies demonstrated that X-OFP has a similar antithrombogenic performance as TFE, but its mechanical properties including adhesion strength of coating-to-substrate are significantly improved, thereby enhancing the stability of the coating. The success of X-OFP will provide a platform to incorporate other different side groups to the polymer backbones and generate new fluorinated polyphosphazene polymers having improved biocompatibility and mechanical properties for coating applications in blood-contacting medical devices. STATEMENT OF SIGNIFICANCE: Implant-induced thrombosis is a major complication of blood-contacting medical devices. This study demonstrated a new fluorinated polyphosphazene coating suitable for the medical device with the significant improvement of the biocompatibility of catheters. Compared to the traditional fluorinated polyphosphazene coating, poly[bis(trifluoroethoxy) phosphazene] (TFE), crosslinkable poly[bis(octafluoropentoxy) phosphazene] (X-OFP) contains a higher amount of fluorocarbon content with the octafluoropentoxy side group and is crosslinkable with the allylphenoxy side group. TFE and X-OFP were applied on central venous catheters as coatings. In vitro and in vivo studies demonstrated that X-OFP has a similar antithrombogenic performance as TFE, but its mechanical properties including adhesion strength of coating-to-substrate are significantly improved, thereby enhancing the stability of the coating.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta biomaterialiaPub Date : 2025-07-28DOI: 10.1016/j.actbio.2025.07.059
Hongyu Yang, Chang Peng, Hanjie Sun, Sen Mu, Aiyang Tong, Siqi Wang, Dongkai Wang, Ji Li
{"title":"Nanotechnology-targeted modulation of mitophagy in cancer therapy: Progress and challenges.","authors":"Hongyu Yang, Chang Peng, Hanjie Sun, Sen Mu, Aiyang Tong, Siqi Wang, Dongkai Wang, Ji Li","doi":"10.1016/j.actbio.2025.07.059","DOIUrl":"10.1016/j.actbio.2025.07.059","url":null,"abstract":"<p><p>The clinical efficacy of current cancer treatments remains insufficient, creating an urgent need to identify new therapeutic targets and combine them with traditional treatment methods. Mitophagy, a crucial mechanism for the intracellular clearance of damaged mitochondria, has shown tremendous potential in cancer therapy. However, accurately and effectively regulating mitophagy remains a significant challenge. In some years, nanoparticle-based drug delivery systems have attracted considerable attention due to their high targeting ability and deep tissue penetration. Therefore, applying nanotechnology to regulate mitophagy may offer new therapeutic strategies for cancer treatment. This review provides a comprehensive overview of the recent advances in the targeted regulation of mitophagy using nanotechnology, including the use of nanoparticle carriers alone or in combination with other cancer therapies. Additionally, we discuss the development of mitophagy, the relevant signaling pathways, the relationship between mitophagy and cancer, drugs that modulate mitophagy, and methods for detecting mitophagy. Finally, we explore the prospects and challenges of using nanotechnology to target and regulate mitophagy in cancer therapy. STATEMENT OF SIGNIFICANCE: This review underscores the therapeutic relevance of mitophagy in cancer, focusing on its selective role in mitochondrial quality control and tumor regulation. Given the challenges in precise mitophagy modulation, we highlight the emergence of nanotechnology based delivery systems as a promising solution. The review covers mitophagy mechanisms, associated pathways, detection techniques, mitophagy modu lating agents, and nanoparticle strategies- both standalone and combinatorial. It further discusses translational opportunities and technical barriers, offering a concise, integrative perspective on how nanomedicine can enable targeted mitophagy interventio n for improved cancer therapy.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Structural and mechanical properties of engineered silkworm-spider composite silk.","authors":"Shihua Yu, Xiaoyan Dai, Haodong Wang, Xiaogang Ye, Xiangping Dai, Xinqiu Wang, Huoqing Zheng, Guijun Zhang, Boxiong Zhong","doi":"10.1016/j.actbio.2025.07.056","DOIUrl":"10.1016/j.actbio.2025.07.056","url":null,"abstract":"<p><p>Spider silk demonstrates significant potential for biomaterials and medicinal applications owing to its favorable mechanical properties and biocompatibility. However, spiders are difficult to raise on a large scale, and obtaining silk proteins directly from spiders is inefficient and expensive. A promising strategy for addressing these challenges involves expressing spider silk proteins in transgenic silkworms. In this study, transcription activator-like effector nuclease (TALEN)-mediated genome-targeted editing was employed to separately fuse 1-, 2-, 4-, and eightfold repeats of the cre-MaSp1 gene from black widow spiders to the sericin 1 gene. AlphaFold 3 structure prediction and infrared spectroscopy showed that the β-sheet and helix contents of the composite silk proteins progressively increased with the increase in the number of fused cre-MaSp1 repeats. Mechanical property testing showed that the maximum stress and maximum strain of the silkworm-spider composite silk containing the eightfold cre-MaSp1/Ser1 fusion protein were 39.4 % and 62.2 % higher than those of the wild-type, respectively, representing the best performance among all the lines. This study provides insights into sericin modification and further confirms that the expression of the cre-MaSp1 gene harboring a large number of repeats can improve the mechanical properties of silkworm silk. STATEMENT OF SIGNIFICANCE: Silkworm silk is a kind of natural protein fiber, and the improvement of silk performance is a long-term focus. This study aims to improve the mechanical properties of silk by endowing it with functional proteins through targeted modification of silk proteins. Four different repeats of cre-MaSp1 gene from black widow spiders separately fused into endogenous Ser1 by TALEN-mediated homology-directed recombination. The fusion proteins were successfully expressed and secreted into the cocoon shell. Tensile testing indicated that eightfold cre-MaSp1 repeats significantly increased the maximum stress and strain of the composite silk by 39.4 % and 62.2 % over the wild-type, respectively. Our work provides insights into improving silk properties and expands the potential applications of the silkworm silk gland bioreactor.</p>","PeriodicalId":93848,"journal":{"name":"Acta biomaterialia","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}