Khezina Rafiq, Iqra Sadia, Muhammad Zeeshan Abid, Muhammad Zaryab Waleed, Abdul Rauf, Ejaz Hussain
{"title":"Scientific Insights into the Quantum Dots (QDs)-Based Electrochemical Sensors for State-of-the-Art Applications.","authors":"Khezina Rafiq, Iqra Sadia, Muhammad Zeeshan Abid, Muhammad Zaryab Waleed, Abdul Rauf, Ejaz Hussain","doi":"10.1021/acsbiomaterials.4c01256","DOIUrl":"10.1021/acsbiomaterials.4c01256","url":null,"abstract":"<p><p>Size-dependent optical and electronic properties are unique characteristics of quantum dots (QDs). A significant advantage is the quantum confinement effect that allows their precise tuning to achieve required characteristics and behavior for the targeted applications. Regarding the aforementioned factors, QDs-based sensors have exhibited dramatic potential for the diverse and advanced applications. For example, QDs-based devices have been potentially utilized for bioimaging, drug delivery, cancer therapy, and environmental remediation. In recent years, use of QDs-based electrochemical sensors have been further extended in other areas like gas sensing, metal ion detection, monitoring of organic pollutants, and detection of radioactive isotopes. Objective of this study is to rationalize the QDs-based electrochemical sensors for state-of-the-art applications. This review article comprehensively illustrates the importance of aforementioned devices along with sources from which QDs devices have been formulated and fabricated. Other distinct features of QDs devices are associated with their extremely high active surfaces, inherent ability of reproducibility, sensitivity, and selectivity for the targeted analyte detection. In this review, major categories of QD materials along with justification of their key roles in electrochemical devices have been demonstrated and discussed. All categories have been evaluated with special emphasis on the advantages and drawbacks/challenges associated with QD materials. However, in the interests of readers and researchers, recent improvements also have been included and discussed. On the evaluation, it has been concluded that despite significant challenges, QDs-based electrochemical sensors exhibit excellent performances for state-of-the-art and targeted applications.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580905","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":"Correlating Mechanical Properties and Sequence Motifs in Artificial Spider Silk by Targeted Motif Substitution.","authors":"Hiroyuki Nakamura, Yusuke Ito, Ryota Sato, Hongfang Chi, Chikako Sato, Yasuha Watanabe, Kazuharu Arakawa","doi":"10.1021/acsbiomaterials.4c01389","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01389","url":null,"abstract":"<p><p>The major ampullate silk of orb-weaving spiders is renowned for its exceptional mechanical properties, including high tensile strength and extensibility. The development of artificial spider silk presents a promising alternative to traditional fibers with significant environmental impacts. This study aims to elucidate the relationship between sequence motifs of natural spider silk and the mechanical properties of artificial spider silk. Using the Spider Silkome Database, we identified motifs correlated with specific physical properties and substituted them into MaSp2-based mini-spidroin BP1. We then measured the mechanical properties of the resulting recombinant artificial spider silk through tensile tests, observed structural properties via birefringence measurement and wide-angle X-ray scattering, and evaluated the water response through boiled water shrinkage tests. Introducing a positively correlated motif increased the tensile strength by 9.3%, while a negatively correlated motif decreased it by 5.1%, confirming the sequence-property relationship. These findings demonstrate that targeted motif substitution can effectively control the physical properties of artificial spider silk, facilitating the development of sustainable biomaterials with tailored mechanical properties for diverse industrial applications.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580903","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}
Yunyang Li, Jingwen Wu, Peilin Ye, Yilin Cai, Mingfei Shao, Tong Zhang, Yanchuan Guo, Sujuan Zeng, Janak L Pathak
{"title":"Decellularized Extracellular Matrix Scaffolds: Recent Advances and Emerging Strategies in Bone Tissue Engineering.","authors":"Yunyang Li, Jingwen Wu, Peilin Ye, Yilin Cai, Mingfei Shao, Tong Zhang, Yanchuan Guo, Sujuan Zeng, Janak L Pathak","doi":"10.1021/acsbiomaterials.4c01764","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01764","url":null,"abstract":"<p><p>Bone tissue engineering (BTE) is a complex biological process involving the repair of bone tissue with proper neuronal network and vasculature as well as bone surrounding soft tissue. Synthetic biomaterials used for BTE should be biocompatible, support bone tissue regeneration, and eventually be degraded in situ and replaced with the newly generated bone tissue. Recently, various forms of bone graft materials such as hydrogel, nanofiber scaffolds, and 3D printed composite scaffolds have been developed for BTE application. Decellularized extracellular matrix (DECM), a kind of natural biological material obtained from specific tissues and organs, has certain advantages over synthetic and exogenous biomaterial-derived bone grafts. Moreover, DECM can be developed from a wide range of biological sources and possesses strong molding abilities, natural 3D structures, and bioactive factors. Although DECM has shown robust osteogenic, proangiogenic, immunomodulatory, and bone defect healing potential, the rapid degradation and limited mechanical properties should be improved for bench-to-bed translation in BTE. This review summarizes the recent advances in DECM-based BTE and discusses emerging strategies of DECM-based BTE.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566440","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":"Enhanced Biodegradation of Silk Fibroin Hydrogel for Preventing Postoperative Adhesion.","authors":"Yusuke Kambe, Yusuke Kawano, Makoto Sasaki, Maito Koga, Nobuyuki Fujita, Tsunenori Kameda","doi":"10.1021/acsbiomaterials.4c01805","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01805","url":null,"abstract":"<p><p>An absorbable adhesion barrier is a medical device that prevents postoperative adhesion and matches its biodegradation time with the regeneration period of its target tissues, which is important for antiadhesion effects. Physical hydrogels of <i>Bombyx mori</i> silk fibroin (SF) proteins are degradable <i>in vivo</i>. However, their biodegradation time is too long to exert antiadhesion effects. To shorten the biodegradation time of the SF hydrogels, we decreased the molecular weight (MW) of the SF proteins by alkaline treatment and prepared low-MW (LMW) SF hydrogels. The hydrogels contained less β-sheet crystalline and more amorphous structures than conventional, high-MW (HMW) SF hydrogels. Because of the potential loosened SF molecular structures in the hydrogel networks, the LMW SF hydrogels showed enhanced biodegradation (i.e., shorter <i>in vitro</i> enzymatic biodegradation time and faster <i>in vivo</i> biodegradation rate) as well as a lower affinity for plasma proteins and fibroblasts, which are involved in postoperative adhesion formation. An antiadhesion test using a rat abdominal adhesion model demonstrated that the LMW SF hydrogel applied to the abraded cecum was almost completely degraded within two weeks postimplantation, with a significantly lower adhesion severity score than that in the untreated model rat group. Conversely, the HMW SF hydrogel remained between the cecum and abdominal wall, with the same adhesion severity as that of the untreated model rat group. Therefore, we concluded that the antiadhesion effects of SF hydrogels were induced by enhanced biodegradation. The results of this study indicate the potential of LMW SF hydrogels as absorbable adhesion barriers.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574781","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}
Luping Ren, Junhao Zhang, Lei Nie, Armin Shavandi, Khaydar E Yunusov, Uladzislau E Aharodnikau, Sergey O Solomevich, Yanfang Sun, Guohua Jiang
{"title":"Platelet Membrane-Camouflaged Copper Doped CaO<sub>2</sub> Biomimetic Nanomedicines for Breast Cancer Combination Treatment.","authors":"Luping Ren, Junhao Zhang, Lei Nie, Armin Shavandi, Khaydar E Yunusov, Uladzislau E Aharodnikau, Sergey O Solomevich, Yanfang Sun, Guohua Jiang","doi":"10.1021/acsbiomaterials.4c01362","DOIUrl":"10.1021/acsbiomaterials.4c01362","url":null,"abstract":"<p><p>Breast cancer (BC) is the most frequently diagnosed cancer in women worldwide. Chemodynamic therapy (CDT), photothermal therapy (PTT), and ion interference therapy (IIT), used in combination, represent a common treatment. In this study, platelet membrane-camouflaged copper-doped CaO<sub>2</sub> biomimetic nanomedicines have been developed for breast cancer treatments. Copper-doped CaO<sub>2</sub> nanoparticles were first coated by polydopamine (PDA) and subsequently camouflaged by platelet membrane (PM) to form platelet membrane-camouflaged copper doped CaO<sub>2</sub> biomimetic nanomedicines (Cu-CaO<sub>2</sub>@PDA/PM). The as-fabricated Cu-CaO<sub>2</sub>@PDA/PM multifunctional nanomedicines could decompose within the tumor microenvironment to release Ca<sup>2+</sup> for ion interference therapy, and the generated H<sub>2</sub>O<sub>2</sub> could perform a Fenton-like reaction with the assistance of loaded copper ions to produce ·OH, thus realizing chemodynamic therapy. In addition, the copper ions could also consume glutathione and weaken its ability to scavenge reactive oxygen species, which was conducive to amplifying the effect of oxidative stress. The coating of the polydopamine layer could achieve local hyperthermia of the tumor site, and the surface modification of the platelet membrane could enhance the targeting and biocompatibility of nanomedicines. <i>In vivo</i> and <i>in vitro</i> tests demonstrated that the developed Cu-CaO<sub>2</sub>@PDA/PM biomimetic nanomedicines offer a promising biomimetic nanoplatform for efficient multimodal combination therapy for breast cancer.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566441","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}
Mehmet Serhat Aydin, Nora Marek, Theo Luciani, Samih Mohamed-Ahmed, Bodil Lund, Cecilie Gjerde, Kamal Mustafa, Salwa Suliman, Ahmad Rashad
{"title":"Impact of Porosity and Stiffness of 3D Printed Polycaprolactone Scaffolds on Osteogenic Differentiation of Human Mesenchymal Stromal Cells and Activation of Dendritic Cells.","authors":"Mehmet Serhat Aydin, Nora Marek, Theo Luciani, Samih Mohamed-Ahmed, Bodil Lund, Cecilie Gjerde, Kamal Mustafa, Salwa Suliman, Ahmad Rashad","doi":"10.1021/acsbiomaterials.4c01108","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01108","url":null,"abstract":"<p><p>Despite the potential of extrusion-based printing of thermoplastic polymers in bone tissue engineering, the inherent nonporous stiff nature of the printed filaments may elicit immune responses that influence bone regeneration. In this study, bone scaffolds made of polycaprolactone (PCL) filaments with different internal microporosity and stiffness was 3D-printed. It was achieved by combining three fabrication techniques, salt leaching and 3D printing at either low or high temperatures (LT/HT) with or without nonsolvent induced phase separation (NIPS). Printing PCL at HT resulted in stiff scaffolds (modulus of elasticity (E): 403 ± 19 MPa and strain: 6.6 ± 0.1%), while NIPS-based printing at LT produced less stiff and highly flexible scaffolds (E: 53 ± 10 MPa and strain: 435 ± 105%). Moreover, the introduction of porosity by salt leaching in the printed filaments significantly changed the mechanical properties and degradation rate of the scaffolds. Furthermore, this study aimed to show how these variations influence proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBMSC) and the maturation and activation of human monocyte-derived dendritic cells (Mo-DC). The cytocompatibility of the printed scaffolds was confirmed by live-dead imaging, metabolic activity measurement, and the continuous proliferation of hBMSC over 14 days. While all scaffolds facilitated the expression of osteogenic markers (RUNX2 and Collagen I) from hBMSC as detected through immunofluorescence staining, the variation in porosity and stiffness notably influenced the early and late mineralization. Furthermore, the flexible LT scaffolds, with porosity induced by NIPS and salt leaching, stimulated Mo-DC to adopt a pro-inflammatory phenotype marked by a significant increase in the expression of IL1B and TNF genes, alongside decreased expression of anti-inflammatory markers, IL10 and TGF1B. Altogether, the results of the current study demonstrate the importance of tailoring porosity and stiffness of PCL scaffolds to direct their biological performance toward a more immune-mediated bone healing process.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563500","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}
Ye Zhu, Yong Jiang, Qian Cao*, Hongchi Liu, Lei Lei and Tianmin Guan,
{"title":"Study on Optimization of the Structural Mechanical Properties of Personalized Porous Implant Prosthesis","authors":"Ye Zhu, Yong Jiang, Qian Cao*, Hongchi Liu, Lei Lei and Tianmin Guan, ","doi":"10.1021/acsbiomaterials.4c0026810.1021/acsbiomaterials.4c00268","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c00268https://doi.org/10.1021/acsbiomaterials.4c00268","url":null,"abstract":"<p >Porous implant prostheses can effectively reduce the stress shielding effect. Still, the single elastic modulus prosthesis cannot adapt to the individual skeletal variability, so it is necessary to optimize the structural parameters of the prosthesis to overcome the individual variability. In this regard, this study analyzes the law of structural parameters and mechanical properties after selecting the type of porous structure (diamond structure). It proposes the optimization method of the structural parameters on this basis. First, the functional relationship equations between the unit mass of the porous implant prosthesis, the elastic modulus of the porous implant prosthesis, and the structural parameters were established respectively. Second, the support rod length and radius of the porous implant prosthesis are optimized by a genetic algorithm to form the optimization design method of the porous implant prosthesis. Finally, the feasibility and effectiveness of the optimized design of the porosity implanted prosthesis were verified by animal experiments, and the optimized implanted prosthesis with optimized structural parameters increased bone growth by 20–30% compared to the control group in the animal body. The proposed method provides a theoretical basis and technical support for the rehabilitation of patients and the production of prostheses by physicians.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142609577","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}
Shanguo Zhang, Tianyi Jiang*, Ming Li, Haoxiu Sun, Hao Wu, Wenlong Wu, Yu Li and Hongyuan Jiang,
{"title":"Graphene-Based Wound Dressings for Wound Healing: Mechanism, Technical Analysis, and Application Status","authors":"Shanguo Zhang, Tianyi Jiang*, Ming Li, Haoxiu Sun, Hao Wu, Wenlong Wu, Yu Li and Hongyuan Jiang, ","doi":"10.1021/acsbiomaterials.4c0114210.1021/acsbiomaterials.4c01142","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01142https://doi.org/10.1021/acsbiomaterials.4c01142","url":null,"abstract":"<p >The development of novel wound dressings is critical in medical care. Graphene and its derivatives possess excellent biomedical properties, making them highly suitable for various applications in medical dressings. This review provides a comprehensive technical analysis and the current application status of graphene-based medical dressings. Initially, we discuss the chemical structure and the fabrication method of graphene and its derivatives. We then provide a detailed summary of the mechanisms by which graphene materials promote wound repair across the four stages of wound healing. Subsequently, we categorize the types of graphene-based wound dressings and analyze corresponding characteristics. Finally, we analyze the challenges encountered at present and propose solutions regarding future development trends. This paper aims to serve as a reference for further research in skin tissue engineering and the development of innovative graphene-based medical dressings.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142608702","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}
Mohamad Mokhtarzadegan, Saba Amini, Aida Iraji, Mehdi Kian, Cambyz Irajie, Seyyed Sajad Daneshi, Shekofeh Abbaspour, Shahrokh Zare, Akram Jamshidzadeh, Ali Feiz, Nadiar M. Mussin, Nader Tanideh* and Amin Tamadon*,
{"title":"Enhanced Mandibular Bone Repair Using Poly Lactic-co-glycolic Acid Combined with Nanohydroxyapatite Scaffold Loaded by Mesenchymal Stromal/Stem Cells and Curcumin in Male Rats","authors":"Mohamad Mokhtarzadegan, Saba Amini, Aida Iraji, Mehdi Kian, Cambyz Irajie, Seyyed Sajad Daneshi, Shekofeh Abbaspour, Shahrokh Zare, Akram Jamshidzadeh, Ali Feiz, Nadiar M. Mussin, Nader Tanideh* and Amin Tamadon*, ","doi":"10.1021/acsbiomaterials.4c0060810.1021/acsbiomaterials.4c00608","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c00608https://doi.org/10.1021/acsbiomaterials.4c00608","url":null,"abstract":"<p >This study aimed to investigate the healing effect of a polylactic-<i>co</i>-glycolic acid (PLGA) scaffold containing nanohydroxyapatite (NHA) along with curcumin (CCM), loaded with adipose-derived mesenchymal stem cells (AD-MSCs), on mandibular bone defects. The designed PLGA scaffolds containing NHA were evaluated for their mechanical and structural properties. Forty rats were divided into five groups (<i>n</i> = 8) based on the treatment: Sham, PLGA scaffolds containing NHA, PLGA scaffolds containing NHA + CCM, PLGA scaffolds containing NHA + AD-MSCs, and PLGA scaffolds containing NHA + CCM + AD-MSCs. After 8 weeks’ follow-up, mandible bones were isolated for histomorphometry evaluation. Data were analyzed using SPSS version 21, with <i>p</i>-values <0.05 considered statistically significant. SEM evaluation showed that the designed nanocomposite scaffold had 80% porosity. Histomorphometry results indicated a significant difference in osteocyte, osteoblast, bone area, and vascular area parameters in the group treated with scaffolds loaded with AD-MSCs + CCM compared to the other groups (<i>p</i> < 0.05). The PLGA-containing NHA-CCM nanocomposite scaffold demonstrated good porosity and dispersion, suitable for treating bone defects. Rats treated with scaffolds containing AD-MSCs and CCM showed better therapeutic results than the other groups. Further research is needed to evaluate its anti-inflammatory, antioxidant properties, osteogenesis, and therapeutic effects in larger animal models.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142609033","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}
Shuo Wang, Zhan Yuin Ong, Sheng Qu, Yongjie Wang, Jingguo Xin, Zhi Zheng and Hong Wu*,
{"title":"Omiganan-Based Synthetic Antimicrobial Peptides for the Healthcare of Infectious Endophthalmitis","authors":"Shuo Wang, Zhan Yuin Ong, Sheng Qu, Yongjie Wang, Jingguo Xin, Zhi Zheng and Hong Wu*, ","doi":"10.1021/acsbiomaterials.4c0154410.1021/acsbiomaterials.4c01544","DOIUrl":"https://doi.org/10.1021/acsbiomaterials.4c01544https://doi.org/10.1021/acsbiomaterials.4c01544","url":null,"abstract":"<p >Bacterial endophthalmitis is a severe infection of the aqueous or vitreous humor of the eye that can lead to permanent vision loss. Due to the rapid emergence of antibiotic resistance and dose-limiting toxicities, the standard treatment of bacterial endophthalmitis via the intravitreal injection of broad-spectrum antibiotics remains inadequate. Membrane active cationic antimicrobial peptides (AMPs) have emerged as a promising class of effective and broad-spectrum antimicrobial agents with potential to overcome antibiotic resistance. In this work, we investigate, for the first time, the use of omiganan (IK-12), a 12-amino acid indolicidin derivative for the treatment of bacterial endophthalmitis. Additionally, IK-12 was used as a template to perform amino acid rearrangements, without altering the length or type of amino acids, to yield a series of new derivative AMPs with varying extents of secondary structure formation under membrane mimicking conditions. IK-12 and its derivatives demonstrated strong and broad-spectrum antibacterial activities against a panel of clinically isolated Gram-positive and Gram-negative bacteria, including methicillin-resistant <i>Staphylococcus aureus</i> commonly implicated in bacterial endophthalmitis. Interestingly, two of the new IK-12 derivatives, IP-12 and WP-12, showed lower geometric mean minimum inhibitory concentration and higher 50% hemolysis concentration values, which effectively translated into 2- to 3.4-fold higher bacterial selectivity than the parent IK-12. Furthermore, the intravitreal injection of IK-12, IP-12, and WP-12 in a rabbit model of <i>MRSA</i>-induced endophthalmitis led to considerably improved clinical presentation and reduced recruitment of inflammatory cells. In all, these results demonstrate the potential of IK-12 and its derivatives, IP-12 and WP-12, as promising candidates for the treatment of bacterial endophthalmitis.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142608751","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}