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Tissue-Safe Low-Temperature Plasma Treatment for Effective Management of Mature Peri-Implantitis Biofilms on Titanium Surfaces. 组织安全的低温等离子处理技术,用于有效处理钛表面成熟的种植体周围炎生物膜。
IF 5.4 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-13 DOI: 10.1021/acsbiomaterials.4c01413
Beatriz H D Panariello, Giovanna C Denucci, Caroline C Tonon, George J Eckert, Lukasz Witek, Vasudev V Nayak, Paulo G Coelho, Simone Duarte

The unique screw-shape design and microstructure of implants pose a challenge for mechanical debridement in removing biofilms. Biofilms exhibit increased resistance to antimicrobials relative to single planktonic cells, emphasizing the need for effective biofilm removal during periodontal therapy for peri-implantitis treatment. To tackle this issue, our team evaluated the effectiveness of low-temperature plasma (LTP) for disinfecting titanium discs contaminated with multispecies biofilms associated with peri-implantitis, specifically focusing on biofilms matured for 14 and 21 days as well as biofilms that had formed on Straumann Ti-SLA implants for 21 days. The biofilms included Actinomyces naeslundii, Porphyromonas gingivalis, Streptococcus oralis, and Veillonella dispar, which were grown in anaerobic conditions. These biofilms were subjected to LTP treatment for 1, 3, and 5 min, using distances of 3 or 10 mm from the LTP nozzle to the samples. Control groups included biofilms formed on Ti discs or implants that received no treatment, exposure to argon flow at 3 or 10 mm of distance for 1, 3, or 5 min, application for 1 min of 14 μg/mL amoxicillin, 140 μg/mL metronidazole, or a blend of both, and treatment with 0.12% chlorhexidine (CHX) for 1 min. For the implants, 21-day-old biofilms were treated with 0.12% CHX 0.12% for 1 min and LTP for 1 min at a distance of 3 mm for each quadrant. Biofilm viability was assessed through bacterial counting and confocal laser scanning microscopy. The impact of LTP was investigated on reconstituted oral epithelia (ROE) contaminated with P. gingivalis, evaluating cytotoxicity, cell viability, and histology. The results showed that a 1 min exposure to LTP at distances of 3 or 10 mm significantly lowered bacterial counts on implants and discs compared to the untreated controls (p < 0.017). LTP exposure yielded lower levels of cytotoxicity relative to the untreated contaminated control after 12 h of contamination (p = 0.038), and cell viability was not affected by LTP (p ≥ 0.05); thus, LTP-treated samples were shown to be safe for tissue applications, with low cytotoxicity and elevated cell viability post-treatment, and these results were validated by qualitative histological analysis. In conclusion, the study's results support the effectiveness of 1 min LTP exposure in successfully disinfecting mature peri-implantitis multispecies biofilms on titanium discs and implants. Moreover, it validated the safety of LTP on ROE, suggesting its potential as an adjunctive treatment for peri-implantitis.

种植体独特的螺纹设计和微观结构给机械清创去除生物膜带来了挑战。与单个浮游细胞相比,生物膜对抗菌剂的耐药性更强,因此在治疗种植体周围炎的牙周治疗过程中需要有效清除生物膜。为了解决这个问题,我们的团队评估了低温等离子体(LTP)对被与种植体周围炎相关的多菌种生物膜污染的钛盘进行消毒的效果,特别关注成熟 14 天和 21 天的生物膜,以及在 StraumannⓇ Ti-SLA 种植体上形成 21 天的生物膜。这些生物膜包括在厌氧条件下生长的奈氏放线菌、牙龈卟啉单胞菌、口腔链球菌和Veillonella dispar。对这些生物膜进行 1、3 和 5 分钟的 LTP 处理,LTP 喷嘴与样品的距离为 3 或 10 毫米。对照组包括在钛盘或植入物上形成的生物膜,这些生物膜未接受任何处理;在 3 或 10 毫米的距离内暴露于氩气流 1、3 或 5 分钟;使用 14 μg/mL 阿莫西林、140 μg/mL 甲硝唑或两者的混合物 1 分钟;使用 0.12% 洗必泰 (CHX) 处理 1 分钟。对于种植体,用 0.12% CHX 0.12% 处理 21 天的生物膜 1 分钟,然后用 LTP 处理 1 分钟,每个象限的距离为 3 毫米。通过细菌计数和共聚焦激光扫描显微镜评估生物膜的活力。研究了 LTP 对受牙龈脓胞污染的重建口腔上皮(ROE)的影响,评估了细胞毒性、细胞活力和组织学。结果表明,与未经处理的对照组相比,在距离为 3 毫米或 10 毫米处接触 LTP 1 分钟可显著降低种植体和牙盘上的细菌数量(p < 0.017)。与未处理的污染对照组相比,LTP 污染 12 小时后产生的细胞毒性水平较低(p = 0.038),细胞存活率不受 LTP 影响(p ≥ 0.05);因此,经 LTP 处理的样品可安全用于组织应用,处理后细胞毒性较低,细胞存活率较高,组织学定性分析也验证了这些结果。总之,研究结果表明,暴露 1 分钟的 LTP 可以成功消毒钛盘和种植体上成熟的种植体周围炎多菌种生物膜。此外,研究还验证了 LTP 对 ROE 的安全性,表明它有可能成为种植体周围炎的辅助治疗方法。
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引用次数: 0
Forum: Flexible Bioelectronics with a Focus on Europe 论坛:聚焦欧洲的柔性生物电子学
IF 8.3 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-13 DOI: 10.1021/acsami.4c1783510.1021/acsami.4c17835
Sabine Szunerits,  and , Osvaldo N. Oliveira Jr., 
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引用次数: 0
Advanced Preparation Methods and Biomedical Applications of Single-Atom Nanozymes. 单原子纳米酶的先进制备方法和生物医学应用。
IF 5.4 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-13 DOI: 10.1021/acsbiomaterials.4c01530
Chun-Nan Zhu, Xin Chen, Yong-Qiang Xu, Fei Wang, Dong-Yun Zheng, Chao Liu, Xue-Hao Zhang, Yu Yi, Dong-Bing Cheng

Metal nanoparticles with inherent defects can harness biomolecules to catalyze reactions within living organisms, thereby accelerating the advancement of multifunctional diagnostic and therapeutic technologies. In the quest for superior catalytic efficiency and selectivity, atomically dispersed single-atom nanozymes (SANzymes) have garnered significant interest recently. This review concentrates on the development of SANzymes, addressing potential challenges such as fabrication strategies, surface engineering, and structural characteristics. Notably, we elucidate the catalytic mechanisms behind some key reactions to facilitate the biomedical application of SANzymes. The diverse biomedical uses of SANzymes including in cancer therapy, wound disinfection, biosensing, and oxidative stress cytoprotection are comprehensively summarized, revealing the link between material structure and catalytic performance. Lastly, we explore the future prospects of SANzymes in biomedical fields.

具有固有缺陷的金属纳米粒子可以利用生物分子催化生物体内的反应,从而加速多功能诊断和治疗技术的发展。为了追求更高的催化效率和选择性,原子分散的单原子纳米酶(SANzymes)最近引起了人们的极大兴趣。这篇综述集中探讨了 SANzymes 的开发,解决了制造策略、表面工程和结构特征等潜在挑战。值得注意的是,我们阐明了一些关键反应背后的催化机理,以促进 SANzymes 的生物医学应用。我们全面总结了 SANzymes 在癌症治疗、伤口消毒、生物传感和氧化应激细胞保护等方面的多种生物医学用途,揭示了材料结构与催化性能之间的联系。最后,我们探讨了 SANzymes 在生物医学领域的未来前景。
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引用次数: 0
Materials Science and Environmental Applicability 材料科学与环境适用性
IF 8.9 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-12 DOI: 10.1021/acs.estlett.4c0087310.1021/acs.estlett.4c00873
Peng Wang*, Jiang Xu, Wenbin Wang, Tanju Karanfil, Michael S. Wong, Virender K. Sharma and Rajnish Kumar, 
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引用次数: 0
Correction to "Injectable Self-Harden Antibiofilm Bioceramic Cement for Minimally Invasive Surgery". 对 "用于微创手术的可注射自硬抗生物膜生物陶瓷水泥 "的更正。
IF 5.4 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-11 Epub Date: 2024-10-07 DOI: 10.1021/acsbiomaterials.4c01735
Xiaofang Li, Zexu Ma, Congping Wu, Mei Zhang, Yitong Wang, Guangxun Zheng, Mengxin Zhu, Guangda Li, Fangfang Fu, Xueqin Hao
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引用次数: 0
Electrospinning Recombinant Spider Silk Fibroin-Reinforced PLGA Membranes: A Biocompatible Scaffold for Wound Healing Applications. 电纺丝重组蜘蛛丝纤维蛋白增强聚乳酸乙二醛(PLGA)膜:用于伤口愈合的生物相容性支架。
IF 5.4 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-11 Epub Date: 2024-10-22 DOI: 10.1021/acsbiomaterials.4c01605
Yuanyuan Chen, Emma J Murphy, Zhi Cao, Ciara Buckley, Yvonne Cortese, Bor Shin Chee, Thomas Scheibel

Polylactide-polyglycolide (PLGA) is one of the most attractive polymeric biomaterials used to fabricate medical devices for drug delivery and tissue engineering applications. Nevertheless, the utilization of PLGA in load-bearing applications is restricted due to its inadequate mechanical properties. This study examines the potential of recombinant silk fibroin (eADF4), a readily producible biomaterial, as a reinforcing agent for PLGA. The PLGA/eADF4 composite membranes were developed by using the process of electrospinning. The spinnability of the electrospinning solutions and the physicochemical, mechanical, and thermal properties of the composite membranes were characterized. The addition of eADF4 increased the viscosity of the electrospinning solutions and enhanced both the mechanical characteristics and the thermal stability of the composites. This study demonstrates that PLGA membranes reinforced with recombinant spider silk fibroin are noncytotoxic, significantly enhance cell migration and wound closure, and do not trigger an inflammatory response, making them ideal candidates for advanced wound healing applications.

聚乳酸-聚乙二醇(PLGA)是最具吸引力的聚合物生物材料之一,可用于制造药物输送和组织工程应用的医疗器械。然而,由于其机械性能不足,PLGA 在承重应用中的使用受到了限制。本研究探讨了重组蚕丝纤维素(eADF4)作为 PLGA 增强剂的潜力。PLGA/eADF4 复合膜是通过电纺丝工艺制成的。研究人员对电纺溶液的可纺性以及复合膜的物理化学、机械和热性能进行了表征。添加 eADF4 增加了电纺丝溶液的粘度,提高了复合材料的机械特性和热稳定性。这项研究表明,用重组蜘蛛丝纤维蛋白增强的聚乳酸乙丙橡胶(PLGA)膜无细胞毒性,能显著促进细胞迁移和伤口闭合,而且不会引发炎症反应,是先进伤口愈合应用的理想候选材料。
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引用次数: 0
Form Equals Function: Influence of Coacervate Architecture on Drug Delivery Applications. 形式等于功能:凝聚态结构对药物输送应用的影响
IF 5.4 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-11 Epub Date: 2024-10-18 DOI: 10.1021/acsbiomaterials.4c01105
Chaeyoung Lim, Whitney C Blocher McTigue

Complex coacervates, formed through electrostatic interactions between oppositely charged polymers, present a versatile platform for drug delivery, providing rapid assembly, selective encapsulation, and responsiveness to environmental stimuli. The architecture and properties of coacervates can be tuned by controlling structural and environmental design factors, which significantly impact the stability and delivery efficiency of the drugs. While environmental design factors such as salt, pH, and temperature play a crucial role in coacervate formation, structural design factors such as polymer concentration, polymer structure, mixing ratio, and chain length serve as the core framework that shapes coacervate architecture. These elements modulate the phase behavior and material properties of coacervates, allowing for a highly tunable system. In this review, we primarily analyze how these structural design factors contribute to the formation of diverse coacervate architecture, ranging from bulk coacervates to polyion complex micelles, vesicles, and cross-linked gels, though environmental design factors are considered. We then examine the effectiveness of these architectures in enhancing the delivery and efficacy of drugs across various administration routes, such as noninvasive (e.g., oral and transdermal) and invasive delivery. This review aims to provide foundational insights into the design of advanced drug delivery systems by examining how the origin and chemical structure of polymers influence coacervate architecture, which in turn defines their material properties. We then explore how the architecture can be tailored to optimize drug delivery for specific administration routes. This approach leverages the intrinsic properties derived from the coacervate architecture to enable targeted, controlled, and efficient drug release, ultimately enhancing therapeutic outcomes in precision medicine.

通过带相反电荷的聚合物之间的静电作用形成的复杂共水合物是一种多功能的给药平台,具有快速组装、选择性封装和对环境刺激反应灵敏等特点。可以通过控制结构和环境设计因素来调整凝聚态的结构和特性,这些因素对药物的稳定性和递送效率有重大影响。盐分、pH 值和温度等环境设计因素在凝聚态形成过程中起着至关重要的作用,而聚合物浓度、聚合物结构、混合比例和链长等结构设计因素则是形成凝聚态结构的核心框架。这些因素可调节共水合物的相行为和材料特性,从而形成一个高度可调的系统。在本综述中,我们主要分析了这些结构设计因素是如何促进形成各种不同的共渗结构的,包括从团状共渗物到多离子复合胶束、囊泡和交联凝胶,当然也考虑了环境设计因素。然后,我们将研究这些结构在提高各种给药途径(如非侵入性给药(如口服和透皮给药)和侵入性给药等)的给药效果和药效方面的有效性。本综述旨在通过研究聚合物的来源和化学结构如何影响凝聚态结构,进而确定其材料特性,为先进给药系统的设计提供基础性见解。然后,我们将探讨如何调整结构以优化特定给药途径的给药效果。这种方法利用了凝聚态结构的固有特性,实现了药物的定向、可控和高效释放,最终提高了精准医疗的治疗效果。
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引用次数: 0
Specific Degradation of the Mucin Domain of Lubricin in Synovial Fluid Impairs Cartilage Lubrication. 滑膜液中润滑蛋白粘蛋白域的特异性降解会损害软骨的润滑性。
IF 5.4 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-11 Epub Date: 2024-10-19 DOI: 10.1021/acsbiomaterials.4c00908
Megh Prajapati, Karan Vishwanath, Lingting Huang, Marshall Colville, Heidi Reesink, Matthew Paszek, Lawrence J Bonassar

Progressive cartilage degradation, synovial inflammation, and joint lubrication dysfunction are key markers of osteoarthritis. The composition of synovial fluid (SF) is altered in OA, with changes to both hyaluronic acid and lubricin, the primary lubricating molecules in SF. Lubricin's distinct bottlebrush mucin domain has been speculated to contribute to its lubricating ability, but the relationship between its structure and mechanical function in SF is not well understood. Here, we demonstrate the application of a novel mucinase (StcE) to selectively degrade lubricin's mucin domain in SF to measure its impact on joint lubrication and friction. Notably, StcE effectively degraded the lubricating ability of SF in a dose-dependent manner starting at nanogram concentrations (1-3.2 ng/mL). Further, the highest StcE doses effectively degraded lubrication to levels on par with trypsin, suggesting that cleavage at the mucin domain of lubricin is sufficient to completely inhibit the lubrication mechanism of the collective protein component in SF. These findings demonstrate the value of mucin-specific experimental approaches to characterize the lubricating properties of SF and reveal key trends in joint lubrication that help us better understand cartilage function in lubrication-deficient joints.

软骨逐渐退化、滑膜发炎和关节润滑功能障碍是骨关节炎的主要标志。骨关节炎患者的滑液(SF)成分会发生改变,滑液中的主要润滑分子透明质酸和润滑蛋白也会发生变化。据推测,润滑蛋白独特的底丛粘蛋白结构域有助于提高其润滑能力,但其结构与滑液中机械功能之间的关系尚不十分清楚。在这里,我们展示了应用新型粘蛋白酶(StcE)选择性降解SF中润滑蛋白的粘蛋白结构域,以测量其对关节润滑和摩擦的影响。值得注意的是,StcE从纳米浓度(1-3.2纳克/毫升)开始以剂量依赖的方式有效降解SF的润滑能力。此外,最高剂量的 StcE 能有效降解润滑能力,降解水平与胰蛋白酶相当,这表明裂解润滑蛋白的粘蛋白结构域足以完全抑制 SF 中集体蛋白成分的润滑机制。这些发现证明了粘蛋白特异性实验方法在表征 SF 润滑特性方面的价值,并揭示了关节润滑的关键趋势,有助于我们更好地了解润滑缺陷关节的软骨功能。
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引用次数: 0
Thermo-controlled Water Microenvironment Inducing Fluorescence Enhancement of Chalcone Nanohydrogels for Mitochondrial Temperature Sensing. 用于线粒体温度传感的查耳酮纳米水凝胶的热控水微环境诱导荧光增强作用
IF 5.4 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-11 Epub Date: 2024-10-15 DOI: 10.1021/acsbiomaterials.4c01427
Qing-Pu Zhang, Qingqing Zhang, Yu-Ling Sun, Xin Tao, Yu-Ting Zhao, Fei Guo, Zhen-Ke Li, Zhen Wang, Zi-Hui Liang, Chang-Hai Yi

Developing aggregation-induced emission (AIE)-based hydrogels that exhibit fluorescence enhancement as to thermal properties is an interesting and challenging task. In this work, we employed the fluorophore 2'-hydroxychalcone (HC), fluorescence properties of which are easily influenced by the excited-state intramolecular proton transfer and twisted intramolecular charge transfer (TICT) effects, to develop a novel type of temperature-sensitive polymers, hydroxychalcone-based polymers (HCPs). By controlling the temperature-dependent water microenvironments in HCPs, the intramolecular hydrogen bonds between water and HCPs can be regulated, thereby influencing the TICT process and leading to thermo-induced fluorescence enhancement, which shows a contrary tendency compared to typical AIEgens that always exhibit fluorescence attenuation as the thermal energy accelerates the molecular motion. Following the decoration with triphenylphosphine, the resulting polymer P-HCP assembled into nanohydrogels and served as a fluorescent probe for intracellular mitochondrial temperature sensing.

开发基于聚合诱导发射(AIE)的水凝胶,使其在热特性方面表现出荧光增强效果,是一项既有趣又具有挑战性的任务。在这项工作中,我们利用荧光团 2'-羟基查尔酮(HC)(其荧光特性很容易受到激发态分子内质子转移和扭曲分子内电荷转移(TICT)效应的影响)来开发一种新型的温度敏感聚合物--羟基查尔酮基聚合物(HCPs)。通过控制 HCPs 中与温度相关的水微环境,可以调节水和 HCPs 之间的分子内氢键,从而影响 TICT 过程,导致热诱导荧光增强,这与典型的 AIEgens(由于热能加速分子运动,因此始终表现出荧光衰减)相比,呈现出相反的趋势。用三苯基膦装饰后,得到的聚合物 P-HCP 组装成纳米水凝胶,可作为荧光探针用于细胞内线粒体温度传感。
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引用次数: 0
Treatment of Bone Defects and Nonunion via Novel Delivery Mechanisms, Growth Factors, and Stem Cells: A Review. 通过新型输送机制、生长因子和干细胞治疗骨缺损和骨不连:综述。
IF 5.4 2区 医学 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-11-11 DOI: 10.1021/acsbiomaterials.4c01279
Quinn T Ehlen, Joseph P Costello, Nicholas A Mirsky, Blaire V Slavin, Marcelo Parra, Albert Ptashnik, Vasudev Vivekanand Nayak, Paulo G Coelho, Lukasz Witek

Bone nonunion following a fracture represents a significant global healthcare challenge, with an overall incidence ranging between 2 and 10% of all fractures. The management of nonunion is not only financially prohibitive but often necessitates invasive surgical interventions. This comprehensive manuscript aims to provide an extensive review of the published literature involving growth factors, stem cells, and novel delivery mechanisms for the treatment of fracture nonunion. Key growth factors involved in bone healing have been extensively studied, including bone morphogenic protein (BMP), vascular endothelial growth factor (VEGF), and platelet-derived growth factor. This review includes both preclinical and clinical studies that evaluated the role of growth factors in acute and chronic nonunion. Overall, these studies revealed promising bridging and fracture union rates but also elucidated complications such as heterotopic ossification and inferior mechanical properties associated with chronic nonunion. Stem cells, particularly mesenchymal stem cells (MSCs), are an extensively studied topic in the treatment of nonunion. A literature search identified articles that demonstrated improved healing responses, osteogenic capacity, and vascularization of fractures due to the presence of MSCs. Furthermore, this review addresses novel mechanisms and materials being researched to deliver these growth factors and stem cells to nonunion sites, including natural/synthetic polymers and bioceramics. The specific mechanisms explored in this review include BMP-induced osteoblast differentiation, VEGF-mediated angiogenesis, and the role of MSCs in multilineage differentiation and paracrine signaling. While these therapeutic modalities exhibit substantial preclinical promise in treating fracture nonunion, there remains a need for further research, particularly in chronic nonunion and large animal models. This paper seeks to identify such translational hurdles which must be addressed in order to progress the aforementioned treatments from the lab to the clinical setting.

骨折后的骨不愈合是全球医疗保健面临的一项重大挑战,其总体发生率占所有骨折的 2% 到 10%。处理骨不连不仅经济上难以承受,而且往往需要进行侵入性手术干预。本综合手稿旨在对已发表的涉及生长因子、干细胞和治疗骨折不愈合的新型给药机制的文献进行广泛综述。涉及骨愈合的主要生长因子已被广泛研究,包括骨形态形成蛋白(BMP)、血管内皮生长因子(VEGF)和血小板衍生生长因子。本综述包括评估生长因子在急性和慢性骨不连中作用的临床前和临床研究。总体而言,这些研究显示了良好的桥接率和骨折愈合率,但也阐明了与慢性不愈合相关的异位骨化和机械性能低下等并发症。干细胞,尤其是间充质干细胞(MSCs),是治疗骨折不愈合的一个广泛研究课题。通过文献检索发现,有文章表明间充质干细胞的存在改善了骨折的愈合反应、成骨能力和血管化。此外,本综述还探讨了将这些生长因子和干细胞输送到骨不连部位的新机制和新材料,包括天然/合成聚合物和生物陶瓷。本综述探讨的具体机制包括BMP诱导的成骨细胞分化、血管内皮生长因子介导的血管生成以及间充质干细胞在多线分化和旁分泌信号中的作用。虽然这些治疗方式在治疗骨折不愈合方面显示出了巨大的临床前前景,但仍需进一步研究,尤其是在慢性不愈合和大型动物模型中。本文旨在找出必须解决的转化障碍,以便将上述疗法从实验室推向临床。
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引用次数: 0
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