ACS Biomaterials Science & Engineering最新文献

{"title":"Exploring the Antimicrobial Potential of LL-37 Derivatives: Recent Developments and Challenges","authors":"Yihao Yuan,&nbsp;Jiapeng Li,&nbsp;Guotao Wei,&nbsp;Ziyi Shen,&nbsp;Bo Li*,&nbsp;Jiawei Wu* and Jing Liu,&nbsp;","doi":"10.1021/acsbiomaterials.4c0202910.1021/acsbiomaterials.4c02029","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c02029https://doi.org/10.1021/acsbiomaterials.4c02029","url":null,"abstract":"<p >The human antimicrobial peptide LL-37 exhibits broad antimicrobial efficacy. However, it has several limitations including high production costs, reduced efficacy under physiological conditions, susceptibility to proteolytic degradation and significant toxicity to human cells. Recent research has improved the clinical potential of peptide LL-37 through multiple systematic modifications. Therefore, we review the various modification techniques for LL-37 and explore the structure–activity relationships that underpin its antimicrobial properties. We also highlight the benefits of LL-37 derivatives and investigate their mechanisms of action against bacterial infections, particularly their effects on biofilms and cell membranes. Furthermore, we review the antimicrobial applications of LL-37 derivatives, examine nanocarrier systems for their delivery, and highlight the potential synergy between these derivatives and traditional antibiotics. Finally, it assesses the status of LL-37 derivatives in clinical applications, identifies ongoing challenges, and provides insights into future modifications and potential applications. This review aims to offer valuable strategies for enhancing LL-37 derivatives and facilitating their transition from laboratory research to clinical practice.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"11 6","pages":"3145–3164 3145–3164"},"PeriodicalIF":5.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144238722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction of “Nanogrooved Elastomeric Diaphragm Arrays for Assessment of Cardiomyocytes under Synergistic Effects of Circular Mechanical Stimuli and Electrical Conductivity to Enhance Intercellular Communication”","authors":"Abdullah-Bin Siddique,&nbsp;Keith A. Williams and Nathan S. Swami*,&nbsp;","doi":"10.1021/acsbiomaterials.5c0090610.1021/acsbiomaterials.5c00906","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00906https://doi.org/10.1021/acsbiomaterials.5c00906","url":null,"abstract":"","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"11 6","pages":"3785 3785"},"PeriodicalIF":5.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsbiomaterials.5c00906","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144239062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication of a ZnO/Polydopamine/ε-Polylysine Coating with Good Corrosion Resistance and a Joint Antibacterial Pathway on the Surface of Medical Stainless Steel","authors":"Jinglin Zhang*,&nbsp;Shuoyan Jiang,&nbsp;Huidi Liu,&nbsp;Zengxi Wang,&nbsp;Xiang Cai and Shaozao Tan*,&nbsp;","doi":"10.1021/acsbiomaterials.5c0008710.1021/acsbiomaterials.5c00087","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00087https://doi.org/10.1021/acsbiomaterials.5c00087","url":null,"abstract":"<p >Medical stainless steel (SS) is a widely used alloy in orthopedic and dental implant applications. However, SS can cause local corrosion in the body, which may affect cell proliferation and differentiation, and is prone to related bacterial infection. Therefore, surface modification is required to improve the corrosion resistance and antibacterial performance of SS to extend its service life. To achieve this goal, a new type of composite coating was established on the surface of SS. First, zinc oxide (ZnO) nanoparticles were deposited on the surface of SS by electrochemical deposition. Then, polydopamine (PDA) was formed through the self-polymerization of dopamine. Finally, the Michael addition reaction between ε-polylysine (ε-PL) and PDA was used to chemically graft a cationic antimicrobial peptide (AMP), namely, ε-PL, constructing a corrosion-resistant and antibacterial ZnO/PDA/ε-PL coating on the surface of the SS (SZP/ε-PL). The results indicated that the obtained composite coating could significantly improve the corrosion resistance of SS because of the introduction of ZnO. After being irradiated with near-infrared (NIR) light (wavelength: 1064 nm, power: 1 W/cm²) for 8 min, the temperature of SZP/ε-PL increased from 22.4 to 57.8 °C. Moreover, there was no significant temperature decay after four cycles, which indicated the good photothermal performance and stability of SZP/ε-PL owing to the function of PDA. Combining photothermal sterilization and AMP contact sterilization, the antibacterial rates of SZP/ε-PL against <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> both reached nearly 100%. In addition, SZP/ε-PL has excellent blood compatibility. With the above advantages, SZP/ε-PL was expected to become a safe and efficient implant material.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"11 6","pages":"3351–3363 3351–3363"},"PeriodicalIF":5.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144238895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Unique Extracellular Matrix Composition of Acomys as a Potential Key to Resisting Fibrosis","authors":"Michele N. Dill,&nbsp;Zoe Turner,&nbsp;Paulina W. Kapuscinska,&nbsp;Katie Heiden,&nbsp;Kari B. Basso,&nbsp;Chelsey S. Simmons and Erika Moore*,&nbsp;","doi":"10.1021/acsbiomaterials.5c0081010.1021/acsbiomaterials.5c00810","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00810https://doi.org/10.1021/acsbiomaterials.5c00810","url":null,"abstract":"<p >Fibrosis is a dysregulated wound healing response characterized by excessive accumulation of dense scar tissue that inhibits organ function and is estimated to contribute to up to 45% of deaths in the industrialized world. In this work, we sought to uncover new ways to address fibrosis by drawing inspiration from an animal that does not develop fibrosis. The Spiny Mouse (<i>Acomys</i>) has the most extensive regenerative capabilities of any known mammal and can regenerate injuries to the skin, kidney, heart, skeletal muscle, and spine with little to no fibrosis. We hypothesize that the regenerative abilities of <i>Acomys</i> are due, in part, to altered stiffness-mediated fibroblast-to-myofibroblast transition (FMT). In this work, we interrogated stiffness-mediated FMT in <i>Acomys</i> and <i>Mus</i> dermal fibroblasts <i>in vitro</i> by performing RNA Sequencing and found no differential gene expression in <i>Acomys</i> fibroblasts cultured on soft vs stiff substrates. We further investigated the direct impact of stiffness-mediated FMT and species differences on ECM deposition by fabricating cell-derived matrices (CDMs) from <i>Acomys</i> and <i>Mus</i> fibroblasts cultured on varying stiffnesses. After assessing the composition of these CDMs using label-free quantitative proteomics, fibrosis-associated extracellular matrix proteins including fibrillin-1, ADAMTS1, SPARC, and galectin-1 were found to be significantly reduced or absent in <i>Acomys</i> CDMs compared to <i>Mus</i> CDMs. In addition, proteins that have been connected to fibrosis resolution, including Col12a1 and clusterin, were upregulated in <i>Acomys</i> CDMs. When cultured on <i>Acomys</i> CDMs, mouse macrophages downregulated MMP9 mRNA expression and maintained increased expression of iNOS in response to IL-4, a pro-fibrotic cytokine. These results indicate a direct impact of species-specific ECM compositions on macrophage phenotype and suggest that ECM produced by <i>Acomys</i> fibroblasts may impede the development of a pro-fibrotic macrophage phenotype in the presence of pro-fibrotic stimuli.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"11 6","pages":"3616–3633 3616–3633"},"PeriodicalIF":5.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144238841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Sensory Neuron-Integrated Skin Spheroid Model for the Evaluation of Neuropeptide-Based Topical Delivery Systems","authors":"Bianca Aparecida Martin,&nbsp;Juliana Viegas,&nbsp;Luciana Facco Dalmolin,&nbsp;Emerson de Souza Santos,&nbsp;Izabela Pereira Vatanabe,&nbsp;Sabrina Francesca Lisboa,&nbsp;Renata Fonseca Vianna Lopez and Bruno Sarmento*,&nbsp;","doi":"10.1021/acsbiomaterials.5c0014110.1021/acsbiomaterials.5c00141","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00141https://doi.org/10.1021/acsbiomaterials.5c00141","url":null,"abstract":"<p >The skin is a complex organ composed of multiple layers and diverse cell types, including keratinocytes, fibroblasts, adipocytes, and sensory neurons, which maintain its structural and functional integrity together. Conventional in vitro and ex vivo models help investigate drug permeation and selected biological effects. However, they are limited in replicating neural interactions critical for assessing the efficacy of neuropeptide-based therapies. To address this limitation, a sensory neuron-integrated skin spheroid (SS) model was established, incorporating key skin cell types and providing a rapid, adaptable, and physiologically relevant platform for screening the biological activity of topical delivery systems targeting neuronal pathways. The model’s responsiveness was demonstrated using acetyl hexapeptide-3 (HEX-3), a neuropeptide that inhibits acetylcholine release. HEX-3 was internalized by spheroid cells, with preferential accumulation around sensory neurons, confirming targeted cellular uptake. In parallel, ex vivo human skin studies confirmed that HEX-3 can traverse the stratum corneum and accumulate in deeper layers. Treatment with this film enhanced skin hydration, reduced scaling, and improved the structural organization of the stratum corneum after 48 h. Functional assays using the SS model showed that HEX-3 treatment suppressed acetylcholine release, upregulated the antioxidant enzyme SOD2, and stimulated type I collagen synthesis. In aged skin samples, the application of HEX-3 significantly increased collagen levels. This effect was mirrored in the spheroid model, which reached collagen levels comparable to those of aged human skin upon treatment. These findings establish the SS model as a robust platform for evaluating the biological activity of neuropeptide-based topical therapies, offering valuable insights for developing advanced strategies for skin rejuvenation and repair.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"11 6","pages":"3503–3522 3503–3522"},"PeriodicalIF":5.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144238443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Five-In-One Hydrogel Integrating Bacteriostasis, Self-Healing Capability, Growth Factor Release, Electrical Stimulation, and Photothermal Stimulation Tailored for Complex Wound Repair","authors":"Simin Lai,&nbsp;Chenxi Shi,&nbsp;Liting Yuan,&nbsp;Kefeng Li,&nbsp;Xiaojing Wang,&nbsp;Xi Yu,&nbsp;Pengbi Liu,&nbsp;Huan Wang,&nbsp;Lihuan Wang* and Hui Yu*,&nbsp;","doi":"10.1021/acsbiomaterials.5c0024410.1021/acsbiomaterials.5c00244","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00244https://doi.org/10.1021/acsbiomaterials.5c00244","url":null,"abstract":"<p >Complex wound management remains a significant global challenge, and the development of multifunctional wound dressings that can effectively promote wound healing remains an urgent clinical need. Herein, a kind of multifunctional hydrogel wound dressing that combines bacteriostasis, self-healing capability, growth factor release, electrical stimulation, and photothermal stimulation is developed. This kind of wound dressing is generated by adding protocatechualdehyde (protocatechuic aldehyde (PA)), short core–shell fibers loading with platelet-rich-plasma (platelet-rich plasma fibers), and polydopamine-coated carbon nanotubes (PDA@CNTs) into quaternary ammonium chitosan (QCS) solution to form a shear-reversibly cross-linked QCS/PA/PDA@CNTs-PRP hydrogel. The obtained hydrogels possess impressive properties, including high swelling capacity (445–852%), strong adhesion ability (16.4–36.7 kPa), self-healing ability, injectability, conductivity (0.24–0.46 S/m), and photothermal properties. Notably, under near-infrared irradiation, the hydrogel exhibits a highly efficient bactericidal activity. In vitro experiments demonstrated that the hydrogel exhibits excellent biocompatibility and anti-inflammatory capability as well as its ability to stimulate cell proliferation, migration, and tubule formation. Moreover, the in vivo studies further confirmed that with the additional assistance of near-infrared light and electrical stimulation, the hydrogel further promotes wound epithelization, angiogenesis, and collagen deposition. Consequently, this hydrogel provides a promising therapeutic strategy for complex wound healing.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"11 6","pages":"3709–3725 3709–3725"},"PeriodicalIF":5.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144238717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electric Stimulation Combined with Biomaterials for Repairing Spinal Cord Injury","authors":"Lulu Du,&nbsp;Liya Zhang,&nbsp;Shengzhe Bao,&nbsp;Fangsu Yan,&nbsp;Wenwei Jiang,&nbsp;Hui Wang* and Chuanming Dong*,&nbsp;","doi":"10.1021/acsbiomaterials.5c0061510.1021/acsbiomaterials.5c00615","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00615https://doi.org/10.1021/acsbiomaterials.5c00615","url":null,"abstract":"<p >Spinal cord injury (SCI) is a central nervous system (CNS) disease with a high disability rate, and reconstructing motor function after SCI remains a global challenge. Recent advancements in rehabilitation and regenerative medicine offer new approaches to SCI repair. Electrical stimulation has been shown to alter cell membrane charge distribution, generating action potentials, and affecting cell behavior. This method aids axon regeneration and neurotrophic factor upregulation, crucial for nerve repair. Biomaterials, used as scaffolds or coatings in cell culture and tissue engineering, enhance cell proliferation, migration, differentiation, and tissue regeneration. Electroactive biomaterials combined with electrical stimulation show promise in regenerating nerve, heart, and bone tissues. In this paper, different types of electrical stimulation and biomaterials applied to SCI are described, and the current application and research progress of electrical stimulation combined with biomaterials in the treatment of SCI are described, as well as the future prospects and challenges.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"11 6","pages":"3276–3296 3276–3296"},"PeriodicalIF":5.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144238510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinspired Silk and Human Amniotic Membrane-Based MSC-sEV-Functionalized Wound Dressing Enhances Skin Regeneration: A Cell-Free Therapeutic Modality for Wound Care","authors":"Shruti Mahapatra,&nbsp;Yashvi Sharma,&nbsp;Seema Kashyap and Sujata Mohanty*,&nbsp;","doi":"10.1021/acsbiomaterials.5c0035310.1021/acsbiomaterials.5c00353","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00353https://doi.org/10.1021/acsbiomaterials.5c00353","url":null,"abstract":"<p >Full-thickness wounds pose significant healing challenges due to their impaired regenerative capacity, persistent inflammation, and oxidative stress. Enhancing the bioactivity of silk fibroin (SF) and the mechanical strength of the human amniotic membrane (hAM) can improve wound healing outcomes. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) offer promising anti-inflammatory and antioxidant benefits, but their poor retention and painful application limits their clinical utility. To overcome these challenges, we developed a composite scaffold of SF and hAM (Sh), loaded with sEVs (ShE), designed to accelerate wound healing by modulating inflammation, oxidative stress, and tissue regeneration. ShE exhibited excellent physical stability, optimal swelling, degradation kinetics, hemocompatibility, and sustained sEV release. <i>In vitro</i>, it enhanced keratinocyte and fibroblast proliferation and migration, reduced oxidative stress, and provided immunomodulatory and pro-angiogenic effects. ShE significantly lowered ROS levels, suppressed PHA-activated PBMNC proliferation, facilitated macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, and promoted angiogenesis. <i>In vivo</i>, ShE accelerated wound closure within 21 days, outperforming DuoDERM, a commercial dressing. Histopathological analysis demonstrated improved epidermal maturation, dermal regeneration, and reduced scarring in ShE-treated wounds, confirming the superior tissue regeneration capacity. Additionally, its fabrication from medical waste and indigenous raw materials ensures cost-effectiveness and sustainability in healthcare applications. By synergistically regulating cell physiology for skin regeneration, ShE emerges as a promising, clinically viable, and affordable wound dressing for enhanced wound care management.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"11 6","pages":"3597–3615 3597–3615"},"PeriodicalIF":5.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144238716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilizing Extracellular Vesicles from Phaeodactylum tricornutum as a Novel Approach for Protecting the Skin from Oxidative Damage","authors":"Ran Xu,&nbsp;Ying Lu,&nbsp;Luyun Cai* and Litao Zhang,&nbsp;","doi":"10.1021/acsbiomaterials.4c0234610.1021/acsbiomaterials.4c02346","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c02346https://doi.org/10.1021/acsbiomaterials.4c02346","url":null,"abstract":"<p >Oxidative stress is a principal factor contributing to skin damage induced by deleterious stimuli, including ultraviolet (UV) radiation. Microalgae-derived extracellular vesicles (EVs), particularly those from <i>Phaeodactylum tricornutum</i> (PTEV), are gaining recognition as a potential therapeutic avenue for restoring skin homeostasis, owing to their scalable production and multifaceted biological activities. This study evaluates the therapeutic effects of PTEV on oxidative damage in H₂O₂-stimulated HaCaT cells and UV-exposed KM mouse models, based on the extraction and characterization of PTEV. Subsequently, the oxidative stress injury model of HaCaT cells induced by H₂O₂ and the acute photodamage model of KM mice skin induced by UV were established. The results show that HaCaT cells exhibit a time-dependent uptake of PTEV, confirming that PTEV is nontoxic and has the potential for intercellular cross-boundary regulation. Treatment with PTEV can enhance the vitality of H₂O₂-stimulated HaCaT cells, reduce intracellular ROS levels, and increase antioxidant enzyme activity in the cells. Further evaluation revealed that PTEV can inhibit UV-induced thickening of the epidermis and degradation of collagen fibers in mice by suppressing the overexpression of matrix metalloproteinase (MMP-3) induced by UV. It enhances the expression of type I collagen (COL1A1) and increases the activity of antioxidant enzymes, as well as the overall antioxidant capacity of tissues. Additionally, PTEV reduces the increase in malondialdehyde levels and lowers the expression levels of inflammatory factors TNF-α and IL-6, thereby protecting the skin barrier and function in mice with acute photodamage. Continuous production of PTEV offers promising applications in therapeutic strategies.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"11 6","pages":"3400–3415 3400–3415"},"PeriodicalIF":5.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144238436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polylysine Derivatives with a Potent Antibacterial Ability for Effectively Treating Methicillin-Resistant Staphylococcus aureus-Induced Endophthalmitis","authors":"Ting Hua,&nbsp;Rui Wan,&nbsp;Chengcheng Chai,&nbsp;Ran Li,&nbsp;Shuo Wang,&nbsp;Yi Tang,&nbsp;Tianzi Zhang* and Hong Wu*,&nbsp;","doi":"10.1021/acsbiomaterials.5c0042210.1021/acsbiomaterials.5c00422","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.5c00422https://doi.org/10.1021/acsbiomaterials.5c00422","url":null,"abstract":"<p >Bacterial endophthalmitis (BE) is a severe ocular infection that can lead to irreversible blinding ocular disease. When diagnosed with BE, the main treatment approach is empirically administering intravitreal antibiotic injections. However, the excessive use of antibiotics leads to increased drug resistance in pathogens, and the retinal dose-limiting toxicities greatly limit its application in clinic. In this work, we present a series of polylysine derivatives (PLL-<i>n</i>) for the treatment of bacterial endophthalmitis. By precisely adjusting the balance of hydrophilic/hydrophobic, the optimal polymer, PLL-2, demonstrates high efficacy against <i>Staphylococcus aureus</i> (<i>S. aureus</i>), <i>Escherichia coli</i> (<i>E. coli</i>), and various clinically isolated drug-resistant bacteria. The antibacterial mechanism showed that PLL-2 could effectively destroy the bacterial membrane and lead to bacterial death. Due to its unique antibacterial mechanism, PLL-2 exhibits rapid bactericidal kinetics and does not induce bacterial resistance up to 16 generations. More importantly, PLL-2 showed a significant therapeutic effect on a methicillin-resistant <i>S. aureus</i>-induced rat endophthalmitis model, which presents a promising therapeutic approach for managing endophthalmitis.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":"11 6","pages":"3752–3761 3752–3761"},"PeriodicalIF":5.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144238347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}