Acta Biomaterialia最新文献

{"title":"Corrole-based photothermal nanocomposite hydrogel with nitric oxide release for diabetic wound healing","authors":"Haixia Yang ,&nbsp;Qing Chen ,&nbsp;Huaqiong Qiang ,&nbsp;Bo Wang ,&nbsp;Junyang Chen ,&nbsp;Yingling Xie ,&nbsp;Liyan Peng ,&nbsp;Huanhuan Zhao ,&nbsp;Jian Tian","doi":"10.1016/j.actbio.2024.12.020","DOIUrl":"10.1016/j.actbio.2024.12.020","url":null,"abstract":"<div><div>The management of chronic diabetic wounds remains a significant challenge due to persistent bacterial infections and impaired angiogenesis. Herein, we reported a nanocomposite hydrogel (M/P-SNO/G) incorporated with M/P-SNO nanoparticles engineered by supramolecular assembly of the photosensitizing mono-carboxyl corrole (MCC) and S-nitrosothiol-modified polyethylene glycol (mPEG-SNO) for synergistic photothermal therapy (PTT)/nitric oxide (NO) treatment of diabetic wounds. The strong π-π interaction among aggregated MCC in M/P-SNO enhances the optical absorption and photothermal ability, thereby facilitating the precise release of NO upon laser irradiation. The hydrogel matrix, composed of oxidized hyaluronic acid and carboxymethyl chitosan crosslinked by Schiff-base, demonstrates good injectability and self-healing characteristics, providing an ideal environment for wound repair. As expected, M/P-SNO/G exhibits a desirable photothermal performance and a controlled laser-responsive NO release, realizing enhanced bactericidal effect and anti-biofilm ability <em>in vitro</em>. In a full-thickness skin defect model on diabetic mice, M/P-SNO/G has proven effective in bacteria clearance and angiogenesis, significantly accelerating wound healing. This study presents a feasible supramolecular strategy to develop diabetic wound dressings with synergistic PTT/NO treatment.</div></div><div><h3>Statement of significance</h3><div>Developing advanced dressings that simultaneously eliminate bacteria and accelerate wound recovery is essential for treating diabetic wounds. This study developed a nanocomposite hydrogel (M/P-SNO/G) featuring the synergistic effect of photothermal therapy (PTT) and nitric oxide (NO) treatment to accelerate infected diabetic wound healing. M/P-SNO nanoparticles within the hydrogel are self-assembled through the hydrophobic photosensitizing mono-carboxyl corrole (MCC) and the hydrophilic NO-releasing polymer (mPEG-SNO), where highly aggregated MCC molecules ensure superior photothermal performance. Meanwhile, the temperature increase induced by the photothermal effect activates NO release from the hydrogel. Under 660 nm laser irradiation, M/P-SNO/G demonstrates a PTT/NO synergy to effectively inhibit bacterial proliferation and promote angiogenesis, offering significant benefits in diabetic wound repair and further expanding the biomedical applications of corroles.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 431-445"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142802410","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":"Aggregation-prone antimicrobial peptides target gram-negative bacterial nucleic acids and protein synthesis","authors":"Pengyu Chen ,&nbsp;Tianmeng Zhang ,&nbsp;Chunyuan Li ,&nbsp;Praveen Praveen ,&nbsp;Kathy Parisi ,&nbsp;Chia Beh ,&nbsp;Siyang Ding ,&nbsp;John D. Wade ,&nbsp;Yuning Hong ,&nbsp;Sihui Li ,&nbsp;Jackson Nkoh Nkoh ,&nbsp;Andrew Hung ,&nbsp;Wenyi Li ,&nbsp;Chenjing Shang","doi":"10.1016/j.actbio.2024.12.002","DOIUrl":"10.1016/j.actbio.2024.12.002","url":null,"abstract":"<div><div>Aggregation of antimicrobial peptides (AMPs) enhances their efficacy by destabilising the bacterial cell wall, membrane, and cytosolic proteins. Developing aggregation-prone AMPs offers a promising strategy to combat antibiotic resistance, though predicting such AMPs and understanding bacterial responses remain challenging. <em>Octopus bimaculoides</em>, a cephalopod species, lacks known AMP gene families, yet its protein fragments were used to predict AMPs <em>via</em> artificial intelligence tools. Four peptides (Oct-P1, Oct-P2, Oct-P3, and Oct-P4) were identified based on their aggregation propensity. Among them, Oct-P2 reduced the viability of <em>Escherichia coli</em> and <em>Staphylococcus aureus</em> by up to 90 %, confirmed by confocal laser scanning microscopy and scanning electron microscopy. It further aggregated plasmid DNA <em>in vitro</em>, and the presence of extracellular DNA reduced their antibacterial activity. With knockout mutants, it revealed that Oct-P2 was internalized into bacterial cells, possibly through membrane transport proteins, enhancing its antibacterial effect. Aggregation-induced emission assays and molecular dynamics simulations revealed that Oct-P2 aggregates with transcription promoter DNA, inhibiting transcription and translation <em>in vitro</em>. This dual-target mechanism not only highlights the potential of Oct-P2 as a lead template for new antimicrobial drug development, but also opens a new window for discovering AMPs from protein fragments against the upcoming challenge of bacterial infections.</div></div><div><h3>Statement of significance</h3><div>A popular strategy for identifying antimicrobial peptides (AMPs) in specific genomes uses the conserved regions of AMP families, but this strategy has limitations in organisms lacking classical AMP gene families, such as Octopus. Fragments from non-antimicrobial proteins serve as a rich source for the identification of new AMPs. In this study, we used artificial intelligence tools to search for potential candidate AMP sequences from non-antimicrobial proteins in <em>Octopus bimaculoides</em>. The successful identification of aggregation-prone AMPs was shown to decrease bacterial viability, increase permeability, and reduce biomass. One candidate, Oct-P2, kills the gram-negative bacteria <em>E. coli</em> by aggregating with DNA and inhibiting transcription and translation, suggesting a new intracellular mechanism of AMP activity.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 446-460"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786891","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":"Fluorinated polyethyleneimine vectors with serum resistance and adjuvant effect to deliver LMP2 mRNA vaccine for nasopharyngeal carcinoma therapy","authors":"Suleixin Yang ,&nbsp;Ruie Chen ,&nbsp;Yi Wu ,&nbsp;Xiangrong Song ,&nbsp;Xingchen Peng ,&nbsp;Meiwan Chen","doi":"10.1016/j.actbio.2024.12.022","DOIUrl":"10.1016/j.actbio.2024.12.022","url":null,"abstract":"<div><div>Latent membrane protein 2 (LMP2), which is an important protein of Epstein-Barr virus (EBV) in the latent phase to mediate metastasis and recurrence, has shown great potential as a targeting antigen in mRNA vaccine for nasopharyngeal carcinoma (NPC) therapy. In this study, an LMP2 mRNA vaccine was developed based on a serum-resistant fluorinated polyethyleneimine (^TKPF) with the self-adjuvant effect for achieving a strong anti-tumor immunity in NPC treatment. Specifically, the proposed vaccine PEG[^TKPF/mLMP2] was comprised of a ^TKPF/mLMP2 core formed by the cationic ^TKPF and LMP2 mRNA, together with a dialdehyde poly (ethyl glycol) (OHC-PEG-CHO) coating. PEG[^TKPF/mLMP2] showed less protein absorption to enable serum resistance to maintain ∼50 % transfection efficiency under 50 % FBS media. In addition, PEG[^TKPF/mLMP2] could render enhanced internalization and lysosomal escape of mRNA by DC cells <em>via</em> positive charge and fluorine groups, followed by efficient transfection and expression, eventually triggering DC maturation and antigen presentation to T cells as demonstrated by <em>in vitro</em> studies. The activated antigen-specific T cells would attack tumor cells expressing LMP2 and release pro-inflammatory cytokines including IFN-γ, IL-6, and TNF-α. Furthermore, <em>in vivo</em> studies manifested effective spleen transfection and activated T cells by PEG[^TKPF/mLMP2] to prevent tumor cell growth and prolong mouse survival in both prophylactical and therapeutical models. Notably, PEG[^TKPF] revealed self-adjuvant effect to induce a strong immune response for boosting the anti-tumor potency of LMP2 mRNA. In summary, the fabricated LMP2 mRNA vaccine facilitated by the efficient and self-adjuvant vector induced robust immunotherapeutic efficacy, providing a possible solution for NPC therapy.</div></div><div><h3>Statement of Significance</h3><div>Latent membrane protein 2 (LMP2), which is a key Epstein-Barr virus (EBV) protein for metastasis and recurrence, can be targeted as an antigen for mRNA vaccine development to treat nasopharyngeal carcinoma (NPC). However, the current LMP2 vaccine is still inefficient in inducing potent anti-NPC immunity. Although mRNA has emerged as an effective tool to rejuvenate LMP2 vaccine development, it still suffers from vulnerability to serum conditions and weak immune response. In this study, we developed an LMP2 mRNA vaccine based on a serum-resistant fluorinated polyethyleneimine (^TKPF) with self-adjuvant effects to achieve strong anti-tumor immunity in NPC treatment. The proposed PEG[^TKPF/mLMP2] vaccine efficiently delivers to dendritic cells (DCs) for activating T cell maturation, ultimately suppressing the growth of LMP2-expressing tumors in both prophylactic and therapeutic mouse models.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 340-352"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808800","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":"Osteogenic tailoring of oriented bone matrix organization using on/off micropatterning for osteoblast adhesion on titanium surfaces","authors":"Tadaaki Matsuzaka,&nbsp;Aira Matsugaki,&nbsp;Kazuhiko Ishihara,&nbsp;Takayoshi Nakano","doi":"10.1016/j.actbio.2024.12.017","DOIUrl":"10.1016/j.actbio.2024.12.017","url":null,"abstract":"<div><div>Titanium (Ti) implants are well known for their mechanical reliability and chemical stability, crucial for successful bone regeneration. Various shape control and surface modification techniques to enhance biological activity have been developed. Despite the crucial importance of the collagen/apatite bone microstructure for mechanical function, antimicrobial properties, and biocompatibility, precise and versatile pattern control for regenerating the microstructure remains challenging. Here, we developed a novel osteogenic tailoring stripe-micropatterned MPC-Ti substrate that induces genetic-level control of oriented bone matrix organization. This biomaterial was created by micropatterning 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer onto a titanium (Ti) surface through a selective photoreaction. The stripe-micropatterned MPC-Ti substrate establishes a distinct interface for cell adhesion, robustly inducing osteoblast cytoskeleton alignment through actin cytoskeletal alignment, and facilitating the formation of a bone-mimicking-oriented collagen/apatite tissue. Moreover, our study revealed that this bone alignment process is promoted through the activation of the Wnt/β-catenin signaling pathway, which is triggered by nuclear deformation induced by strong cellular alignment guidance. This innovative material is essential for personalized next-generation medical devices, offering high customizability and active restoration of the bone microstructure.</div></div><div><h3>Statement of Significance</h3><div>This study demonstrates a novel osteogenic tailoring stripe-micropatterned MPC-Ti substrate that induces osteoblast alignment and bone matrix orientation based on genetic mechanism. By employing a light-reactive MPC polymer, we successfully micropatterned the titanium surface, creating a biomaterial that stimulates unidirectional osteoblast alignment and enhances the formation of natural bone-mimetic anisotropic microstructures. The innovative approach of regulating cell adhesion and cytoskeletal alignment activates the Wnt/β-catenin signaling pathway, crucial for both bone differentiation and orientation. This study presents the first biomaterial that artificially induces the construction of mechanically superior anisotropic bone tissue, and it is expected to promote functional bone regeneration by enhancing bone differentiation and orientation—targeting both the quantity and quality of bone tissue.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 487-500"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792970","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":"Lysozyme-targeted liposomes for enhanced tubular targeting in the treatment of acute kidney injury","authors":"Qianqian Guo ,&nbsp;Kedui Geng ,&nbsp;Jiangmin Wan ,&nbsp;Tianyu Lan ,&nbsp;Xin Lu ,&nbsp;Ling Tao ,&nbsp;Kunyuan Duan ,&nbsp;Wen Zhou ,&nbsp;Honglei Guo ,&nbsp;Xiangchun Shen","doi":"10.1016/j.actbio.2024.12.026","DOIUrl":"10.1016/j.actbio.2024.12.026","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is defined by the release of pro-inflammatory factors, leading to structural damage in renal tubules and subsequent tubular cell injury and death. Delivering drugs specifically to renal tubules to mitigate tubular cell damage holds potential for AKI treatment. In this work, we developed functional liposomes (LZM-PLNPs-TP) designed to bypass the glomerular filtration barrier and target tubules by leveraging the unique structural and pathological characteristics of glomeruli and tubules. LZM-PLNPs-TP, incorporating lysozyme (LZM) and cationic liposome, and carrying the anti-inflammatory and antioxidant drug Triptolide (TP), demonstrated favorable stability, efficient drug release, and good cytocompatibility in wide TP concentrations (0–100 ng/mL). These liposomes exhibited the enhanced renal accumulation, tubular retention, and cellular targeting through endocytosis by peritubular capillary endothelial cells. The administration of LZM-PLNPs-TP at a minimal TP dosage (0.01 mg/kg) demonstrated significant protection through the mitigation of oxidative stress and inflammation in ischemia/reperfusion injury (IRI) mice, while the naked TP (0.01 mg/kg) exhibited lower efficacy. Following treatment with LZM-PLNPs-TP, levels of serum creatine, blood urea nitrogen, superoxide dismutase, malondialdehyde, as well as the inflammatory cytokines IL-1β and IL-6 in renal IRI mice were found to be significantly reduced by factors of 2.9, 1.7, 0.7, 1.3, 2.1, and 1.9, respectively, compared to mice treated with TP alone. In summary, this study presents an LZM-targeted drug delivery system that synergistically enhances tubular reabsorption and cellular uptake, offering a promising strategy for AKI treatment.</div></div><div><h3>Statement of significance</h3><div>We have designed specialized liposomes (LZM-PLNPs-TP) with targeting capabilities towards renal tubules to enhance cellular internalization, offering a promising therapeutic strategy for AKI treatment. Our research confirms that the increased accumulation of LZM-PLNPs-TP in renal tubules is facilitated by peritubular capillary endothelial cells rather than glomerular filtration. LZM-PLNPs-TP demonstrated effective mitigation of oxidative stress, inflammation suppression, and significant improvement in kidney injury, ultimately leading to the restoration of renal function in murine models of AKI induced by ischemia/reperfusion. This study introduces LZM-targeted liposomes that enhance tubular reabsorption and cellular uptake synergistically, providing a promising therapeutic approach for AKI management.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 394-408"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824106","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":"A metal coordination polymer nanoparticle synergistically re-establishes acidosis and enhances chemodynamic therapy for Glioblastoma","authors":"Yajing Chi ,&nbsp;Chaoqi Song ,&nbsp;Qian Jia ,&nbsp;Ruili Zhang ,&nbsp;Fang Sun ,&nbsp;Zheng Li ,&nbsp;Yuanyuan Jia ,&nbsp;Xian An ,&nbsp;Zhongliang Wang ,&nbsp;Jianxiong Li","doi":"10.1016/j.actbio.2024.11.042","DOIUrl":"10.1016/j.actbio.2024.11.042","url":null,"abstract":"<div><h3>Background</h3><div>Chemodynamic therapy (CDT) has become increasingly important as a tumor treatment strategy, which relies on intracellular acid and hydrogen peroxide to kill tumor cells by generating hydroxyl radicals (·OH) through Fenton/Fenton-like reactions. However, the weakly alkaline intracellular environment considerably caused by the efflux of lactate and <em>H</em>⁺ from glioblastoma cells is not conducive to CDT performance. Intracellular acidification induced by inhibiting the transmembrane monocarboxylate transporter 4 (MCT4) can enhance the therapeutic efficacy of CDT. Existing approaches suffer from insufficient MCT4 inhibition, involve complex drug synthesis, and have many unsatisfactory side effects.</div></div><div><h3>Methods</h3><div>In this study, we constructed an anti-tumor nanoparticle formed by self-assembly driven by the coordination interaction of Fe³⁺ and α-cyano-4-hydroxycinnamate (CHC) to avoid safety issues posed by excessive modification. Fe-CHC nanoparticles were designed to decrease intracellular pH through inhibition of MCT4, which transports lactate/<em>H</em>⁺ to the extracellular space. The resulting intracellular accumulation of lactate and <em>H</em>⁺ led to fatal acidosis and promoted ·OH generated by Fenton/Fenton-like reactions with the presence of the Fe³⁺, thus enhancing CDT-induced tumor cell death.</div></div><div><h3>Results</h3><div><em>In vitro</em> and <em>in vivo</em> results revealed that Fe-CHC exerted a significant synergistic anti-tumor effect by re-establishing acidosis and enhancing CDT in glioblastoma. Furthermore, the decreased <em>H</em>⁺outside the cells caused by the inhibition of lactate/<em>H</em>⁺ efflux hindered extracellular matrix degradation, thereby inhibiting tumor metastasis.</div></div><div><h3>Conclusion</h3><div>Fe-CHC is an effective anti-cancer agent against glioblastoma. This study provides valuable insights for developing acid-modulating anti-tumor nanoparticles, as well as enriching and optimizing the application of CDT in tumor therapy.</div></div><div><h3>Statement of Significance</h3><div>Our study pioneers the Fe-CHC nanoparticle, a metal-coordination polymer that targets MCT4 in glioblastoma cells to restore intracellular acidity and synergize with Fe³⁺ to boost chemodynamic therapy (CDT). Unlike other studies, Fe³⁺ and CHC work together to maximize the therapeutic potential and safety of Fe-CHC with minimal complexity. This innovative approach not only increased the production of reactive oxygen species within tumor cells, but also hindered tumor metastasis. Our work has important scientific implications for tumor microenvironment regulation and the application of CDT, and will provide a promising pathway for the treatment of aggressive cancers and attract a wide audience through its scientific implications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 290-301"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752574","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":"Antibacterial and antifouling materials for urinary catheter coatings","authors":"Qianwen Zhang ,&nbsp;Qida Zong ,&nbsp;Xinke Feng ,&nbsp;Min Luo ,&nbsp;Wei Sun ,&nbsp;Yinglei Zhai","doi":"10.1016/j.actbio.2024.12.040","DOIUrl":"10.1016/j.actbio.2024.12.040","url":null,"abstract":"<div><div>Implantable medical devices have played a significant role in improving both medical care and patients' quality of life. Urinary Catheters (UCs) are commonly utilized as a substitute for bladder drainage and urine collection to prevent urinary retention in patients. However, bacterial colonization and biofilm formation on the catheter surface are prone to occur, leading to catheter-associated urinary tract infections (CAUTIs) and other complications. In recent years, UC coatings have garnered increasing attention. In this review, various antifouling and antibacterial materials for UC coatings are summarized and their impacts on bacterial activities are linked to potential mechanisms of action. Additionally, this review provides an in-depth understanding of the current advancements in UC coatings by presenting the advantages, limitations, notable achievements, and latest research findings. Finally, it anticipates the prospective design and development trajectories of UC coatings in this domain. This holds paramount significance in advancing medical device technology.</div></div><div><h3>Statement of significance</h3><div>Combating catheter-associated urinary tract infections is a major healthcare challenge, and urinary catheter (UC) coatings are considered promising candidates to counter these infections. In this review, various antifouling and antibacterial materials for UCs are summarized, and their impacts on bacterial activities are linked to potential mechanisms of action. Additionally, the review provides an in-depth understanding of the current advancements in UC coatings by presenting the advantages, limitations, notable achievements, and latest research findings. This holds paramount significance in advancing medical device technology.</div><div>This review not only contributes to the scientific research but also sparks interest among readerships and other researchers in the study of safer and more effective UC coatings for improved patient outcomes.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 28-47"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866563","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":"Rapid release of high-valent silver ions from water-soluble porphyrin complexes to enhance the direct killing of Methicillin-Resistant Staphylococcus aureus","authors":"Yanling Lin ,&nbsp;Liyue Liu ,&nbsp;Jiaqi He ,&nbsp;Jianliang Shen ,&nbsp;Qizhi Ren","doi":"10.1016/j.actbio.2024.12.004","DOIUrl":"10.1016/j.actbio.2024.12.004","url":null,"abstract":"<div><div>The emergence of multidrug-resistant (MDR) bacteria represented by MRSA (Methicillin-resistant <em>Staphylococcus aureus</em>) poses a great challenge to current anti-infection treatment. It is critical to develop efficient MRSA anti-bacteria drugs and explore simple therapeutic strategies with low MDR risk. Herein, we synthesized high-valent (Ag^II/Ag^III) water-soluble porphyrins (cationic AgTMPyP and anionic AgTMPPS) and investigated their direct bactericidal property for MRSA without photoactivation <em>in vitro</em> and <em>in vivo.</em> The cationic porphyrin AgTMPyP exhibits well oxidase-like activity and has 100 % sterilizing rate at 8 μmol/L concentration. Besides, AgTMPyP can effectively destroy biofilms <em>in vitro</em>, mediate the polarization of macrophages from M1 to M2, and promote wound healing <em>in vivo</em>. Combined with DFT calculation, the related antibacterial mechanism is further discussed. High-valent silverporphyrins can maintain stable in water for at least 200 days. The moment they encounter MRSA, high-valent silver ions from AgTMPyP can be immediately released from the porphyrin ring and attack the MRSA with efficient sterilization. Together with the hemolysis, blood routine and blood biochemistry tests, it is proved that AgTMPyP can have great prospects in the direct treatment of bacterial infections in skin diseases in the future.</div></div><div><h3>Statement of significance</h3><div>The emergence of multidrug-resistant (MDR) bacteria represented by MRSA poses a great challenge to current anti-infection treatment. It has become critical to develop efficient MRSA anti-bacteria drugs and explore simple therapeutic strategies with low MDR risk. We synthesized high-valent (Ag^II/Ag^III) water-soluble silver porphyrins (AgTMPyP and AgTMPPS), which can be stable for long periods in aqueous solutions. AgTMPyP can directly and efficiently kill bacteria and destroy biofilms without photoactivation <em>in vitro</em> and <em>in vivo</em>. Combined with DFT calculation, the related antibacterial mechanism is further discussed. AgTMPyP is a superior antimicrobial agent with good biocompatibility and it can have great prospects in the direct treatment of bacterial infections and wound healing in the future.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 419-430"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787638","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":"Restoration of physiologic loading after engineered disc implantation mitigates immobilization-induced facet joint and paraspinal muscle degeneration","authors":"Sarah E. Gullbrand ,&nbsp;Ali Kiapour ,&nbsp;Caitlin Barrett ,&nbsp;Matthew Fainor ,&nbsp;Brianna S. Orozco ,&nbsp;Rachel Hilliard ,&nbsp;Robert L. Mauck ,&nbsp;Michael W. Hast ,&nbsp;Thomas P. Schaer ,&nbsp;Harvey E. Smith","doi":"10.1016/j.actbio.2024.12.014","DOIUrl":"10.1016/j.actbio.2024.12.014","url":null,"abstract":"<div><div>Intervertebral disc degeneration is commonly associated with back and neck pain, and standard surgical treatments do not restore spine function. Replacement of the degenerative disc with a living, tissue-engineered construct has the potential to restore normal structure and function to the spine. Toward this goal, our group developed endplate-modified disc-like angle-ply structures (eDAPS) that recapitulate the native structure and function of the disc. While our initial large animal studies utilized rigid internal fixation of the eDAPS implanted level to ensure retention of the eDAPS, chronic immobilization does not restore full function and is detrimental to the spinal motion segment. The purpose of this study was to utilize a goat cervical disc replacement model coupled with finite element modeling of goat cervical motion segments to investigate the effects of remobilization (removal of fixation) on the eDAPS, the facet joints and the adjacent paraspinal muscle. Our results demonstrated that chronic immobilization caused notable degeneration of the facet joints and paraspinal muscles adjacent to eDAPS implants. Remobilization improved eDAPS composition and integration and mitigated, but did not fully reverse, facet joint osteoarthritis and paraspinal muscle atrophy and fibrosis. Finite element modeling revealed that these changes were likely due to reduced range of motion and reduced facet loading, highlighting the importance of maintaining normal spine biomechanical function with any tissue engineered disc replacement.</div></div><div><h3>Statement of significance</h3><div>Back and neck pain are ubiquitous in modern society, and the gold standard surgical treatment of spinal fusion limits patient function. This study advances our understanding of the response of the spinal motion segment to tissue engineered disc replacement with provisional fixation in a large animal model, further advancing the clinical translation of this technology.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 128-139"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803067","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":"Substrate stiffness regulates the proliferation and inflammation of chondrocytes and macrophages through exosomes","authors":"Qiling Lai ,&nbsp;Bo Li ,&nbsp;Linjie Chen ,&nbsp;Yafen Zhou ,&nbsp;Hongdan Bao ,&nbsp;Huaqiong Li","doi":"10.1016/j.actbio.2024.12.021","DOIUrl":"10.1016/j.actbio.2024.12.021","url":null,"abstract":"<div><div>Osteoarthritis (OA) progression is characterized by decreased cartilage stiffness and degradation of the extracellular matrix (ECM), which significantly influence cartilage behavior and fate. In contrast, processes such as chondrocyte calcification and aging often result in increased stiffness. Despite extensive studies on how ECM stiffness regulates cellular functions, the impact of substrate stiffness on the cartilage microenvironment and intercellular communications remains not well understood. Using tunable stiffness Gelatin methacryloyl (GelMA) hydrogel, we demonstrated that a potential optimal substrate stiffness can promote maximal chondrocyte proliferation and exosome secretion. The exogenous addition of stiffness-tuned exosomes induced significant changes in chondrocyte morphology, proliferation, migration, and inflammation. Notably, blocking Yes-associated protein (YAP) synthesis negated the proliferation enhancement induced by exosomes from chondrocytes cultured on medium stiffness substrates (Exo^Medium), confirming that substrate stiffness regulates cell proliferation through exosomes by modulating YAP expression and its nuclear localization. Moreover, our study revealed that exosomes from medium stiffness substrates-mimicking normal cartilage stiffness-not only reduce inflammation in chondrocytes but also shift macrophage polarization from M1 to M2. Conversely, exosomes from soft stiffness substrates, akin to osteoarthritic tissue, exacerbate chondrocytes inflammation and M1 macrophage polarization. These findings highlight the crucial role of stiffness-tuned exosomes in OA progressing, affecting chondrocyte proliferation, migration, inflammation and macrophage polarization, and provide new insights into the potential novel treatment strategies using engineered scaffolds and exosomes.</div></div><div><h3>Statement of significance</h3><div>Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by decreased cartilage stiffness and degradation of the extracellular matrix (ECM). While some studies suggest that increased substrate stiffness enhances cell proliferation, others have reported the opposite effect. Whether there exists an optimal matrix stiffness that promotes chondrocytes anabolism and how matrix stiffness regulates the cartilage microenvironment and intercellular communications remain unclear. Utilizing tunable stiffness Gelatin methacryloyl (GelMA) hydrogel, this study demonstrated that a potential optimal substrate stiffness can maximize chondrocyte proliferation and exosome secretion. The introduction of stiffness-tuned exosomes induced significant changes in chondrocyte and macrophage proliferation, migration, and inflammation, offering new insights into OA progression and highlighting their potential as a promising therapeutic strategy for osteoarthritis treatment and tissue regeneration.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 77-89"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815230","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}