Acta Biomaterialia最新文献

{"title":"Bioinspired Janus Mesh with Mechanical Support and Side-specific Biofunctions for Hernia Repair","authors":"Xiaoli Han ,&nbsp;Zhenliang Liu ,&nbsp;Liwei Sun ,&nbsp;Zexiang Li ,&nbsp;Yanhong Dong ,&nbsp;Lu Zhou ,&nbsp;Lingwan Hao ,&nbsp;Jie Zhao ,&nbsp;Rujian Jiang","doi":"10.1016/j.actbio.2024.12.018","DOIUrl":"10.1016/j.actbio.2024.12.018","url":null,"abstract":"<div><div>Postoperative adhesion (PA) caused by the combination of proteins, inflammatory response and bacterial infection poses substantial challenges for polypropylene meshes (PPMs) based hernioplasty. Herein, inspired by the peritoneum, a Janus PPMs with side-specific functions was developed <em>via</em> a surface-initiated photoiniferter-mediated polymerization technology. A physical barrier composed of zwitterionic polymer brushes (PS) was firstly constructed on the one side of the PPMs, while the polymethacrylic acid (PMAA) brushes acting as the linker for bioactive nanoparticles (HAP) were precisely situated on the opposite surface subsequently. Our findings reveal that the mesh surface modified with PS demonstrated significant antifouling property that more than 99% of protein adhesion could be inhibited even after the co-incubation for 72 h in the crucial test. Meanwhile, on the other surface of the PPMs modified with HAP achieved satisfactory ROS-scavenging, inflammation-inhibiting and cell adhesion-promoting properties as well as good bactericidal performance (killing rate &gt; 99.9%). Furthermore, the Janus PPMs could maintain comparable mechanical property with pristine meshes. Equipped with the above multiple merits and asymmetric property, the constructed Janus PPMs demonstrated effective treatment for abdominal hernia defects <em>in vivo</em> without any PA formation. Overall, this study duplicates the unique characteristics of peritoneum onto PPMs to successfully address postoperative complications of the hernioplasty and also offers a versatile and innovative idea to construct asymmetrical functions on the one implant.</div></div><div><h3>Statement of Significance</h3><div>The implantation of surgical meshes in the hernia defect provides additional firm support to reinforce the abdomen fascia in tension-free way. However, multiple post-surgery complications induced tissue adhesions is of great challenges for commercial mesh-based hernioplasty. Although material designing and surface modification might circumvent these limitations partly, the construction of side-specific biofunctions on the commercial mesh surfaces is very challenging because of its porous structure. Herein, we demonstrate a feasible and promising approach to construct asymmetric biofunctions on the opposite sides of network structured polypropylene mesh, which is rarely achieved previously. The fabricated Janus PPMs maintains the inherent long-term mechanical support; meanwhile, the opposite sides of PPMs could perform multiple biofunctions independently.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 218-234"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796672","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":"Spatial confinement growth of high-performance persistent luminescence nanoparticles for image-guided sonodynamic therapy","authors":"Peng Lin ,&nbsp;Junpeng Shi ,&nbsp;Lin Liu ,&nbsp;Jinyuan Wang ,&nbsp;Zhengxia Yang ,&nbsp;Xia Sun ,&nbsp;Maochun Hong ,&nbsp;Yun Zhang","doi":"10.1016/j.actbio.2024.12.011","DOIUrl":"10.1016/j.actbio.2024.12.011","url":null,"abstract":"<div><div>Near-infrared (NIR) persistent luminescence nanoparticles (PLNPs) have significant potential in diagnostic and therapeutic applications owing to their unique persistent luminescence (PersL). However, obtaining high-performance NIR PLNPs remains challenging because of the limitations of current synthesis methods. Herein, we introduce a spatial confinement growth strategy for synthesizing high-performance NIR PLNPs using hollow mesoporous silica (hmSiO₂). By calcining precursor ions in the hollow cavity, the yolk size of NIR PLNPs was regulated, yielding well-dispersed Zn_1.3Ga_1.4Sn_0.3O₄: Cr_0.005, Y_0.003@hmSiO₂ (ZS) with a yolk-shell structure. Compared to the conventional template method, ZS synthesized via the spatial confinement growth strategy exhibited a 7.7-fold increase in PersL intensity and a threefold increase in specific surface area. As a proof of concept, ZS@PpIX@CaP-AMD (ZPSC-AMD) nanoparticles, with potential for sonodynamic therapy (SDT), were synthesized by loading the sonosensitizer protoporphyrin IX (PpIX) into ZS, coating it with a calcium phosphate (CaP) shell, and modifying it with a tumor-targeting molecule plerixafor (AMD-3100). The tumor enrichment behavior of ZPSC-AMD was monitored by sensitive NIR PersL to guide SDT. Simultaneously, ZPSC-AMD enabled the precise monitoring of tumor accumulation, thereby guiding effective SDT. In addition, Ca²⁺ released from CaP degradation increased the level of reactive oxygen species during SDT, promoting tumor cell apoptosis. This study outlines a reliable design and synthesis approach for high-performance NIR PLNPs and promotes their development in biomedical applications.</div></div><div><h3>Statement of Significance</h3><div>The potential of near infrared (NIR) persistent luminescence nanoparticles (PLNPs) in bio applications is hindered by limitations in the synthesis method. In this article, we proposed a spatial confinement growth strategy of high-performance NIR PLNPs. The obtained PLNPs with yolk-shell structure showed a 7.7-fold increase in PersL intensity and a threefold increase in specific surface area, compared with the commonly used template method. Due to the advantages, sonodynamic therapeutic nanoparticles were constructed based on the above PLNPs, where persistent luminescence was used for ultrasensitive imaging to determine the optimal timing in sonodynamic therapy. In addition, the multifunctional calcium phosphate shell elevated the intracellular reactive oxygen species level to promote tumor cell apoptosis.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 279-289"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792977","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":"Myofibers cultured in viscoelastic hydrogels reveal the effects of integrin-binding and mechanosensing on muscle satellite cells","authors":"Tze-Ling Chang ,&nbsp;Alexandra N. Borelli ,&nbsp;Alicia A. Cutler ,&nbsp;Bradley B. Olwin ,&nbsp;Kristi S. Anseth","doi":"10.1016/j.actbio.2024.11.044","DOIUrl":"10.1016/j.actbio.2024.11.044","url":null,"abstract":"<div><div>Quiescent skeletal muscle satellite cells (SCs) located on myofibers activate in response to muscle injury to regenerate muscle; however, identifying the role of specific matrix signals on SC behavior <em>in vivo</em> is difficult. Therefore, we developed a viscoelastic hydrogel with tunable properties to encapsulate myofibers while maintaining stem cell niche polarity and SC-myofiber interactions to investigate how matrix signals, including viscoelasticity and the integrin-binding ligand arginyl-glycyl-aspartic acid (RGD), influence SC behavior during muscle regeneration. Viscoelastic hydrogels support myofiber culture while preserving SC stemness for up to 72 hours post-encapsulation, minimizing myofiber hypercontraction and SC hyperproliferation compared to Matrigel. Pax7 is continuously expressed in SCs on myofibers embedded in hydrogels with higher stress relaxation while SCs differentiate when embedded in elastic hydrogels. Increasing RGD concentrations activates SCs and translocates YAP/TAZ to the nucleus as revealed by photo-expansion microscopy. Deleting YAP/TAZ abrogates RGD-mediated activation of SCs, and thus, YAP/TAZ mediates RGD ligand-induced SC activation and subsequent proliferation.</div></div><div><h3>Statement of significance</h3><div>Satellite cells (SCs) are responsible for muscle maintenance and regeneration, but how the extracellular matrix regulates SC function is less understood and would benefit from new biomaterial models that can recapitulate the complexity of SC niche <em>in vitro</em>. Upon isolation of myofibers, SCs exit quiescence, becoming activated. To circumvent this issue, we developed a viscoelastic hydrogel for encapsulating myofibers, which maintains SC quiescence and limits differentiation, allowing the study of RGD effects. We showed that increasing RGD concentration promotes activation and suppresses differentiation. Finally, to allow high resolution imaging for resolving the subcellular localization of YAP/TAZ transcriptional co-activators, we applied photo-expansion microscopy and gel-to-gel transfer techniques to quantify YAP/TAZ nuclear-cytoplasmic ratio, revealing that RGD-mediated activation relies on YAP/TAZ nuclear translocation.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 48-60"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775503","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":"Understanding the antibacterial mechanism of metal surfaces","authors":"J.X. Ma,&nbsp;X.L. Chen,&nbsp;M.X. Huang","doi":"10.1016/j.actbio.2024.12.001","DOIUrl":"10.1016/j.actbio.2024.12.001","url":null,"abstract":"<div><div>Bacterial inactivation on antibacterial metal surfaces has been widely used in medicine and daily life to inhibit infection caused by surface contact. However, the underlying antibacterial mechanism of metal surfaces has remained elusive due to a lack of comprehensive theoretical perspectives and direct evidence. Here, we propose a universal understanding of the bacteria-inactivation mechanism of metal surfaces and reveal the changes in bacterial survival behavior with time and spatial location. In terms of bacterial survival over time, we established a quantitative ion influx model and predicted four bacterial survival behaviors based on osmotic pressure changes and ion release. To demonstrate the spatial distribution of bacterial survival, we consider variations in metal antibacterial properties and electrode potentials and design five corrosion galvanic couples to cover all possible metal combinations. The results on the bacterial survival behavior over time confirm our theoretical predictions, exhibiting a dependence of bacterial viability on environmental humidity and metal toxicity. In addition, on the surfaces of galvanic couples, bacteria will experience the most pronounced decrease in viability at anodes, irrespective of the location of the antibacterial metals. This abnormal distribution pattern can be fundamentally attributed to the highest toxic-ion concentration resulting from a low pH at anodes. The consistency between our predictions and observed bacterial survival rates supports the notion that the antibacterial mechanism follows surface ion release and subsequent free-ion influx into the cytoplasm, leading to lethal biochemical reactions in bacteria.</div></div><div><h3>Statement of significance</h3><div>Numerous studies have been conducted on developing antibacterial metals, alloys, and their related applications. However, the underlying antibacterial mechanism of metal surfaces has remained elusive. This work is the first to propose a general understanding of the antibacterial mechanism of metal surfaces, including the temporal and spatial characteristics of bacterial survival behavior. By building a theoretical model, we predicted and confirmed the shapes of the four bacterial survival curves over time. In addition, we found that bacteria have the worst viability loss at the alloy anode, even if non-antibacterial metals occupy this position. The conclusions can provide theoretical support for the antibacterial behavior of metal surfaces, including but not limited to Ag, Cu, Zn, and their corresponding alloys.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"192 ","pages":"Pages 501-512"},"PeriodicalIF":9.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792980","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":"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":"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":"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":"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}