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Adhesive and Wound Healing, Dual Active Hydrogel with Snail Mucus Proteins 粘接和伤口愈合,双活性水凝胶与蜗牛黏液蛋白。
IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-14 DOI: 10.1021/acsabm.5c01923
Oindrila Das, , , Janu Newar, , , Suchanda Verma, , , Gourabamani Swalsingh, , , Aleena Das, , , K. Sony Reddy, , , Naresh Chandra Bal, , and , Archana Ghatak*, 

Many gastropods secrete mucus, which is more viscous and adhesive than the common trail mucus. The primary biochemical distinction between the two types of mucus is the higher protein content of the adhesive mucus. Not enough is known about the function of each of these proteins. In the current study, two of such mucus proteins were isolated from the adhesive mucus of the land snail Macrochlamys indica. In an attempt to imitate the structure of the mucus, these proteins were mixed with commercial hyaluronic acid (HA). The resultant hydrogel was found to have adhesive properties. A cell viability assay revealed that each of the hydrogel components and their mixtures were biologically safe and compatible. The in vitro cell migration assay showed better wound closure in case of the mucus protein as compared to HA, which is already known for its wound healing properties. The hydrogel was used for incision wound healing in mice, followed by histological staining. The result showed faster healing when compared to that of commercial wound healing ointment. In conclusion, this study presents a wound repair material, formulated from snail protein and HA and useful as an adhesive wound dressing with healing effects.

许多腹足类动物分泌黏液,比普通的尾黏液更粘稠。两种黏液的主要生化区别是黏附黏液的蛋白质含量较高。我们对这些蛋白质的功能了解得还不够。本研究从大蜗牛黏液中分离出两种此类黏液蛋白。为了模仿粘液的结构,将这些蛋白质与商业透明质酸(HA)混合。所得的水凝胶被发现具有粘合性能。细胞活力测定显示,每种水凝胶成分及其混合物在生物上是安全的和相容的。体外细胞迁移实验显示,与HA相比,粘液蛋白的伤口愈合效果更好,HA已经以其伤口愈合特性而闻名。将水凝胶用于小鼠切口创面愈合,并进行组织学染色。结果表明,与商业伤口愈合软膏相比,愈合速度更快。总之,本研究提出了一种伤口修复材料,由蜗牛蛋白和透明质酸配制而成,可作为具有愈合作用的粘接性伤口敷料。
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引用次数: 0
Controlling Enzymatic Degradation of Carboxyl-Modified Chitosan and Hyaluronic Acid Biopolymers Using Dynamic Covalent Cross-Linking 动态共价交联控制羧修饰壳聚糖和透明质酸生物聚合物的酶降解。
IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-14 DOI: 10.1021/acsabm.5c01744
Wasitha P. D. W. Thilakarathna, , , Emma G. Welshman, , , Namita Bhasin, , , William Austin, , , Jonah Glazebrook, , , Zeeshan Sheikh, , and , Vahid Adibnia*, 

The enzymatic degradation of hyaluronic acid (HA) and carboxyl-modified chitosan (CC) polymers in aqueous dispersions can be controlled by dynamic covalent cross-linking. Unlike un-cross-linked HA, dynamic covalent cross-linking preserves the viscoelastic behavior of HA dispersions when exposed to hyaluronidase enzyme. Among the dynamic covalent cross-linked CC dispersions, only dispersions with degrees of deacetylation of 98% (CC98) partially upheld the viscoelastic behavior under lysozyme-mediated degradation. Overall, our results suggest that dynamic covalent cross-linking can produce injectable HA and CC dispersions with partial enzymatic degradation resistance.

透明质酸(HA)和羧化壳聚糖(CC)聚合物在水分散体中的酶降解可以通过动态共价交联来控制。与未交联的透明质酸不同,当暴露于透明质酸酶时,动态共价交联保留了透明质酸分散体的粘弹性行为。在动态共价交联CC分散体中,只有去乙酰化程度为98% (CC98)的分散体在溶菌酶介导的降解下部分维持粘弹性行为。总的来说,我们的研究结果表明,动态共价交联可以产生具有部分酶降解抗性的可注射HA和CC分散体。
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引用次数: 0
Engineered Exosomes as Programmable Nanocarriers for Targeted Theranostic and Translational Applications 工程外泌体作为靶向治疗和转化应用的可编程纳米载体。
IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-14 DOI: 10.1021/acsabm.5c01251
Jugal Patil, , , Ankur Singh, , , Satyam Bhalerao, , , Syed Mudasir Ahmad, , , Rakesh M Rawal, , , Dhiraj Bhatia*, , and , Raghu Solanki*, 

Exosomes are nanoscale extracellular vesicles secreted by cells that possess molecular and pathological characteristics of their cellular origin. Acting as natural carriers, they efficiently transport a diverse cargo of biomolecules, including proteins, nucleic acids, lipids, metabolites, and small molecules facilitating highly specific intercellular communication. Owing to their inherent biocompatibility, target specificity, and cargo versatility, exosomes have emerged as one of the most promising platforms for diagnostic and therapeutic applications. This review comprehensively elaborates on intricate biogenesis and regulatory pathways governing exosome production, examines their structural composition and cargo loading preferences, and highlights emerging strategies to enhance their functional capabilities. We further explore recent breakthroughs at the intersection of exosome biology and nanotechnology, emphasizing their roles in maintaining cellular homeostasis, advancing disease diagnostics, and enabling targeted therapeutic delivery. Finally, we critically address current challenges and limitations in exosome research, offering insights into innovative solutions and future directions for their clinical translation.

外泌体是由细胞分泌的纳米级细胞外囊泡,具有细胞起源的分子和病理特征。作为天然载体,它们有效地运输各种生物分子,包括蛋白质、核酸、脂质、代谢物和促进高度特异性细胞间通讯的小分子。外泌体由于其固有的生物相容性、靶向特异性和载物的多功能性,已成为最有前途的诊断和治疗应用平台之一。这篇综述全面阐述了控制外泌体生产的复杂生物发生和调控途径,研究了它们的结构组成和货物装载偏好,并强调了增强其功能能力的新兴策略。我们进一步探讨了外泌体生物学和纳米技术交叉领域的最新突破,强调了它们在维持细胞稳态、推进疾病诊断和实现靶向治疗递送方面的作用。最后,我们批判性地解决当前外泌体研究的挑战和局限性,为其临床翻译提供创新解决方案和未来方向的见解。
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引用次数: 0
Near-Infrared Light-Driven Photocatalytic Antibacterial Activity of CaCO3/C/PDA Nanocomposites against Gram-Negative Bacteria CaCO3/C/PDA纳米复合材料对革兰氏阴性菌的近红外光催化抑菌活性研究
IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-14 DOI: 10.1021/acsabm.5c01840
Zhuoli Chen, , , Lingying Chen, , , Xiaozhi Zheng, , , Junlin Li, , , Jiankun Ding, , , Chen Cai, , and , Haiming Yu*, 

Antibacterial resistance has become a growing global health challenge, with multidrug-resistant pathogens posing significant threats to public health. Traditional antibacterial agents often encounter problems such as high costs, low efficiency, poor antibacterial efficacy, and restricted biocompatibility. Thus, there is an urgent need to develop materials with enhanced antibacterial properties. In this study, CaCO3/C/PDA antibacterial composite was designed as a high-efficacy antibacterial agent against Gram-negative bacteria. Under near-infrared light irradiation (808 nm, 0.3 W/cm2, 4 min), the CaCO3/C/PDA0.2 exhibited satisfactory antibacterial activity against Gram-negative bacteria, including Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumonia, with sterilization rates of 91.7%, 98%, and 100%, respectively. The antibacterial mechanism could be attributed to the synergistic effects of photothermal and photodynamic therapy, where high temperatures can denature bacterial proteins and reactive oxygen species (ROS) may disrupt bacterial metabolism, ultimately leading to bacterial death. All of the experimental results confirmed that CaCO3/C/PDA is a promising antimicrobial agent for Gram-negative bacterial infections. In addition, the in vitro toxicity tests also confirmed that CaCO3/C/PDA possessed excellent biocompatibility. Overall, this work offers an approach and strategy for the development of next-generation antimicrobial materials with broad biomedical potential.

抗菌药物耐药性已成为日益严重的全球卫生挑战,耐多药病原体对公共卫生构成重大威胁。传统抗菌剂往往存在成本高、效率低、抗菌效果差、生物相容性受限等问题。因此,迫切需要开发具有增强抗菌性能的材料。本研究设计了CaCO3/C/PDA抗菌复合材料作为抗革兰氏阴性菌的高效抗菌剂。在808 nm、0.3 W/cm2、4 min的近红外光照射下,CaCO3/C/PDA0.2对大肠杆菌、铜绿假单胞菌、肺炎克雷伯菌等革兰氏阴性菌具有良好的抑菌活性,灭菌率分别为91.7%、98%和100%。抗菌机制可归因于光热和光动力治疗的协同作用,其中高温可使细菌蛋白质变性,活性氧(ROS)可破坏细菌代谢,最终导致细菌死亡。实验结果证实CaCO3/C/PDA是一种很有前景的革兰氏阴性菌感染抗菌药物。此外,体外毒性试验也证实CaCO3/C/PDA具有良好的生物相容性。总的来说,这项工作为开发具有广泛生物医学潜力的下一代抗菌材料提供了一种方法和策略。
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引用次数: 0
Surface Chemistry-Driven Permeation of Nanoparticles Produced by Flash Nanoprecipitation through Mucus Barriers 表面化学驱动的纳米粒子通过黏液屏障的闪蒸沉淀。
IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-13 DOI: 10.1021/acsabm.5c01736
Karla E. Cureño Hernandez, , , Jeonghun Lee, , , Zachary Cartwright, , , Sunghoon Kim, , and , Margarita Herrera-Alonso*, 

Mucosal barriers protect epithelial tissues but limit the diffusion of therapeutic nanoparticles, posing a major challenge for transmucosal drug delivery. Surface chemistry plays a key role in navigating this barrier, where both mucoadhesive and mucopenetrating strategies have shown value. In this study, we demonstrate how combining zwitterionic and boronic acid functionalities enables the rational design of nanoparticles with tunable interactions toward mucus. Block copolymers of poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and poly(carboxybetaine) (PMCB), with or without a terminal aminophenylboronic acid (APBA), were synthesized and used as nanoparticle stabilizers via flash nanoprecipitation using a multi-inlet vortex mixer. Nanoparticle permeation was examined in purified sheep small intestine mucus. PMPC-based nanoparticles exhibited superior transport compared to PMCB- and PEG-containing analogs. Increasing APBA density led to reduced permeation due to specific interactions with mucin-associated sialic acids; this effect was reversed upon preincubation with free sialic acid. Zeta potential analysis before and after mucus exposure confirmed preserved surface integrity regardless of APBA density. These findings highlight the ability to balance mucoadhesive and mucopenetrating properties via surface chemistry, offering a flexible platform for engineering nanoparticles optimized for mucus barrier traversal and downstream targeting in transmucosal drug delivery.

粘膜屏障保护上皮组织,但限制了治疗性纳米颗粒的扩散,这对经黏膜给药构成了重大挑战。表面化学在穿越这一屏障的过程中起着关键作用,黏液粘附和黏液穿透策略都显示出了价值。在这项研究中,我们展示了两性离子和硼酸功能的结合如何使纳米颗粒的合理设计具有可调的对粘液的相互作用。采用多入口涡流混合器,通过闪蒸沉淀法合成了末端氨基苯基硼酸(APBA)或不含末端氨基苯基硼酸(APBA)的聚(2-甲基丙烯酰氧乙基磷酸胆碱)(PMPC)和聚(羧甜菜碱)(PMCB)嵌段共聚物,并将其用作纳米颗粒稳定剂。研究了纳米颗粒在纯化绵羊小肠粘液中的渗透。与含PMCB和peg的类似物相比,基于pmpc的纳米颗粒具有更好的转运能力。由于与黏液相关唾液酸的特异性相互作用,APBA密度增加导致渗透性降低;这种效果在用游离唾液酸预孵育后被逆转。接触黏液前后的Zeta电位分析证实,无论APBA密度如何,表面都保持完整。这些发现强调了通过表面化学平衡黏液粘附和黏液穿透特性的能力,为工程纳米颗粒提供了一个灵活的平台,优化了其在粘膜药物传递中的黏液屏障穿越和下游靶向。
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引用次数: 0
Revolutionizing Wound Care: The Role of Nanotechnology and Biopolymer-Based Materials 革新伤口护理:纳米技术和生物聚合物基材料的作用。
IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-13 DOI: 10.1021/acsabm.5c01412
Prajakta A. Mane, , , Rahul M. Sonavale*, , , Rohan Phatak, , , Nutan Shukla*, , , Zhengyou Li, , , Oleg E. Polozhentsev, , , Carol Cárdenas, , and , Sabrina Belbekhouche*, 

Wound infections represent a significant global healthcare burden, often complicating healing processes and leading to increased morbidity. These infections vary in type, ranging from acute to chronic, surgical site infections, and pressure ulcers, each presenting distinct pathological and microbiological profiles. The primary causative agents include Gram-positive bacteria such as Staphylococcus aureus and Streptococcus pyogenes as well as Gram-negative pathogens such as Pseudomonas aeruginosa and Escherichia coli. Conventional treatment modalities largely rely on systemic or topical antibiotics, debridement of the wound, and antiseptics. However, rising antimicrobial resistance, slow tissue regeneration, and recurrent infections limit the efficacy of these approaches. Recent advances in nanotechnology- and biopolymer-based materials have enhanced wound care options. Biopolymers such as chitosan, alginate, and collagen are valued for their biocompatibility and biodegradability. Chitosan uniquely offers inherent antimicrobial activity, while collagen, alginate, and agarose mainly function as biocompatible scaffolds or drug delivery systems without significant antibacterial properties. When combined with metal nanoparticles, particularly silver, zinc oxide, and gold, these composites exhibit enhanced antibacterial activity, anti-inflammatory effects, and improved wound healing dynamics. Such nanocomposites can be engineered into films, hydrogels, and scaffolds that facilitate moisture retention, controlled drug release, and tissue regeneration, while minimizing cytotoxicity. The integration of nanotechnology with biopolymer science represents a paradigm shift in wound management strategies. This multidisciplinary approach not only addresses the limitations of conventional therapies but also offers tailored, responsive, and effective wound healing platforms. Continued research into the synergistic effects of nanoparticles and natural polymers is essential to fully realize their clinical potential. Ultimately, these innovations could transform wound care, offering patients faster recovery, reduced infection rates, and an improved quality of life. Additionally, hybrid nanocomposites such as hydroxyapatite-based systems have shown enhanced bioactive properties.

伤口感染是一个重大的全球卫生保健负担,往往使愈合过程复杂化并导致发病率增加。这些感染的类型各不相同,从急性到慢性,手术部位感染和压疮,每一种都有不同的病理和微生物特征。主要病原体包括革兰氏阳性细菌,如金黄色葡萄球菌和化脓性链球菌,以及革兰氏阴性病原体,如铜绿假单胞菌和大肠杆菌。传统的治疗方式主要依靠全身或局部抗生素、伤口清创和防腐剂。然而,抗菌素耐药性上升、组织再生缓慢和复发性感染限制了这些方法的有效性。纳米技术和生物聚合物基材料的最新进展增加了伤口护理的选择。生物聚合物如壳聚糖、海藻酸盐和胶原蛋白因其生物相容性和生物可降解性而受到重视。壳聚糖具有独特的抗菌活性,而胶原蛋白、海藻酸盐和琼脂糖主要作为生物相容性支架或药物输送系统,没有明显的抗菌性能。当与金属纳米颗粒,特别是银、氧化锌和金结合时,这些复合材料表现出增强的抗菌活性、抗炎作用和改善伤口愈合动力学。这种纳米复合材料可以制成薄膜、水凝胶和支架,促进水分保持、控制药物释放和组织再生,同时最小化细胞毒性。纳米技术与生物聚合物科学的结合代表了伤口管理策略的范式转变。这种多学科的方法不仅解决了传统疗法的局限性,而且还提供了量身定制的、反应灵敏的、有效的伤口愈合平台。继续研究纳米颗粒和天然聚合物的协同作用对于充分发挥其临床潜力至关重要。最终,这些创新可以改变伤口护理,为患者提供更快的恢复,降低感染率,提高生活质量。此外,混合纳米复合材料,如羟基磷灰石为基础的系统,已显示出增强的生物活性特性。
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引用次数: 0
Tryptophan-Conjugated Carbon Dots with Enhanced Cellular Uptake as a Potential Drug Delivery System for Melanoma 增强细胞摄取的色氨酸共轭碳点作为黑色素瘤潜在的药物递送系统。
IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-13 DOI: 10.1021/acsabm.5c01730
Nasrin Imumkachi, , , Pornpattra Rattanaseth, , , Sawinee Ngernpimai, , , Janpen Thonghlueng, , , Piyaporn Matulakul, , , Pakawat Toomjeen, , , Theerapong Puangmali, , , Raynoo Thanan, , , Tawut Rudtanatip, , , Natthida Weerapreeyakul, , and , Chadamas Sakonsinsiri*, 

Melanoma is a rare but highly aggressive form of skin cancer that can rapidly metastasize, leading to a significant mortality rate. A main challenge in chemotherapy is the lack of selectivity in drug delivery to tumor sites, which affects both tumor and healthy tissues. Developing drug delivery systems (DDS) capable of preferentially interacting with transporters expressed on cancer cells may help address this issue. Carbon dots (CDs) have emerged as promising tools for the advancement of DDS due to their distinctive fluorescent characteristics, good water solubility, biocompatibility, and straightforward fabrication. In this work, CDs were synthesized via a facile method and conjugated with tryptophan (Trp) to evaluate their potential application as a DDS in melanoma. The fabricated CDs were characterized for their size, surface charge, optical properties, functional groups, and elemental analysis. LAT1 expression was examined by immunofluorescence, confirming higher levels in SK-MEL-2 melanoma cells compared to HK-2 normal kidney cells. Biocompatibility was established before conjugating CDs with tryptophan (Trp), ditryptophan (di-Trp), and tritryptophan (tri-Trp) and assessing their size, functional groups, and optical characteristics. Cellular uptake studies showed preferential uptake of Trp-conjugated CDs in SK-MEL-2 cells over HK-2 cells, indicating that tri-Trp-CDs exhibited the highest uptake. Molecular dynamics simulations suggested potential CDs-LAT1 interactions via van der Waals and electrostatic interactions. Trp-conjugated CDs were biocompatible with both SK-MEL-2 and HK-2 cells and could be electrostatically loaded with doxorubicin (DOX), exhibiting enhanced cytotoxicity against SK-MEL-2 cells compared to DOX alone. A trend toward greater selectivity for SK-MEL-2 cells over normal cells was observed, with tri-Trp/DOX showing the most pronounced effect, possibly reflecting LAT1-1 mediated uptake. These findings suggest that Trp-modified CDs may serve as promising DDS candidates for melanoma treatment.

黑色素瘤是一种罕见但侵袭性很强的皮肤癌,可以迅速转移,导致很高的死亡率。化疗的一个主要挑战是药物递送到肿瘤部位缺乏选择性,这既影响肿瘤也影响健康组织。开发能够优先与癌细胞上表达的转运蛋白相互作用的药物传递系统(DDS)可能有助于解决这一问题。碳点(cd)由于其独特的荧光特性、良好的水溶性、生物相容性和简单的制备方法,已成为推进DDS的有前途的工具。在这项工作中,CDs通过一种简单的方法合成,并与色氨酸(Trp)偶联,以评估其作为黑色素瘤DDS的潜在应用。对制备的CDs进行了尺寸、表面电荷、光学性质、官能团和元素分析表征。通过免疫荧光检测LAT1的表达,证实SK-MEL-2黑色素瘤细胞中的LAT1表达水平高于HK-2正常肾细胞。在将CDs与色氨酸(Trp)、二色氨酸(di-Trp)和三色氨酸(tri-Trp)偶联并评估它们的大小、官能团和光学特性之前,建立了生物相容性。细胞摄取研究显示,SK-MEL-2细胞比HK-2细胞更优先摄取trp -共轭CDs,表明tr3 - trp -CDs的摄取最高。分子动力学模拟表明cd - lat1可能通过范德华和静电相互作用相互作用。色氨酸偶联的CDs与SK-MEL-2和HK-2细胞均具有生物相容性,并且可以静电负载多柔比星(DOX),与DOX单独相比,对SK-MEL-2细胞具有增强的细胞毒性。观察到SK-MEL-2细胞比正常细胞有更大的选择性趋势,其中tri-Trp/DOX表现出最明显的效果,可能反映了LAT1-1介导的摄取。这些发现表明,trp修饰的CDs可能是治疗黑色素瘤的有希望的DDS候选者。
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引用次数: 0
Soft, Sustainable, and Sensitive: Biopolymer-Based Hydrogels as Recyclable Temperature Sensors for Skin-Integrated Electronics 柔软,可持续和敏感:基于生物聚合物的水凝胶作为皮肤集成电子产品的可回收温度传感器。
IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-13 DOI: 10.1021/acsabm.5c01607
David Naranjo, , , Juan Torras, , and , Jose García-Torres*, 

The development of sustainable, soft, and recyclable materials for skin-integrated electronics is critical for advancing wearable health monitoring while minimizing electronic waste. Here, chitosan–agarose-based hydrogels integrated with poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) are fabricated as recyclable, biocompatible, and thermoresponsive materials for flexible temperature sensors. The hydrogels are synthesized using a green and easy process, forming interpenetrated dual networks that exhibit high water content, mechanical compliance, and enhanced electroconductivity. Morphological analysis reveals highly porous interconnected structures, while Fourier transform infrared spectroscopy confirms the successful incorporation of PEDOT:PSS. The hydrogels display high swelling capacity, tunable mechanical properties within the physiological range of human skin, and enhanced electrochemical performance. The temperature-sensing capability of the hydrogels demonstrates a negative temperature coefficient of resistance (TCR) of up to −1.5% °C–1, outperforming similar hydrogel-based sensors while maintaining stability over repeated thermal cycles. Importantly, the hydrogels can be disassembled, reprocessed, and reused for multiple sensing cycles without significant loss of performance, demonstrating true recyclability and supporting circular material use in soft electronics. The convergence of natural biopolymers with conducting polymers within these hydrogels provides a promising platform for developing eco-friendly, flexible bioelectronic devices, aligning with the requirements of sustainable materials science while addressing the need for high-performance, soft temperature sensors for wearable healthcare applications.

为皮肤集成电子产品开发可持续、柔软和可回收的材料对于推进可穿戴健康监测,同时最大限度地减少电子废物至关重要。在这里,壳聚糖-琼脂糖基水凝胶与聚(3,4-乙烯二氧噻吩):聚苯乙烯磺酸盐(PEDOT:PSS)集成,作为可回收的,生物相容性和热响应材料,用于柔性温度传感器。水凝胶的合成采用绿色和简单的工艺,形成相互渗透的双重网络,具有高含水量,机械顺应性和增强的导电性。形态学分析显示了高度多孔的互连结构,而傅里叶变换红外光谱证实了PEDOT:PSS的成功结合。该水凝胶具有较高的溶胀能力,在人体皮肤的生理范围内可调节机械性能,并具有增强的电化学性能。水凝胶的温度传感能力显示出高达-1.5%°C-1的负温度电阻系数(TCR),优于类似的基于水凝胶的传感器,同时在重复热循环中保持稳定性。重要的是,水凝胶可以拆卸,再加工,并在多个传感周期中重复使用,而不会显着损失性能,展示了真正的可回收性,并支持循环材料在软电子中的使用。在这些水凝胶中,天然生物聚合物与导电聚合物的融合为开发环保、灵活的生物电子设备提供了一个有前途的平台,符合可持续材料科学的要求,同时满足可穿戴医疗保健应用对高性能、柔软温度传感器的需求。
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引用次数: 0
Synergistic Therapeutic Efficacy of Engineered Probiotics Embedded in Self-Assembling Keratin Hydrogels for Ulcerative Colitis Treatment 嵌入自组装角蛋白水凝胶的工程益生菌治疗溃疡性结肠炎的协同疗效。
IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-12 DOI: 10.1021/acsabm.5c01614
Yijiao Wen, , , Chunhua Zhang, , , Xuanting Wang, , , Yi Shen, , , Huiwen Luo, , , Siyuan Liu, , , Famin Ke, , , Qin Wang*, , and , Xiaowei Gao*, 

Efficient oral delivery and sustained viability of probiotics remain significant obstacles to the clinical translation of live biotherapeutics. Therefore, in this study, we developed self-assembling keratin hydrogels derived from feather waste using a disulfide shuffling strategy for probiotic encapsulation. This cost-effective and scalable approach substantially improved the gastrointestinal tolerance and oral bioavailability of multiple probiotics, including Escherichia coli Nissle 1917 (EcN), Bacillus licheniformis, Lactococcus lactis, and Bifidobacterium bifidum. To achieve site-specific release in the intestinal tract, EcN was engineered to express keratinase (EcNker), enabling hydrogel degradation in the gut. In dextran sulfate sodium-induced colitis model mice, hydrogel-encapsulated EcNker exhibited markedly superior therapeutic efficacy over unencapsulated probiotics, as indicated by the amelioration of clinical symptoms, restoration of colon histology, attenuation of intestinal apoptosis, and normalization of inflammatory cytokine profiles. Mechanistically, hydrogel-encapsulated EcNker treatment restored the gut barrier integrity by upregulating the tight junction protein levels, modulating gut microbiota by increasing the number of beneficial genera, and enhancing short-chain fatty acid production. Collectively, our findings highlight the potential of keratin hydrogels as universal biocompatible and efficient delivery platforms for orally engineered probiotics to treat colonic colitis and other diseases.

有效的口服给药和益生菌的持续生存能力仍然是活体生物治疗药物临床转化的重大障碍。因此,在本研究中,我们利用二硫洗牌策略开发了自组装角蛋白水凝胶,用于益生菌包封。这种具有成本效益和可扩展的方法大大提高了胃肠道对多种益生菌的耐受性和口服生物利用度,包括大肠杆菌、地衣芽孢杆菌、乳酸乳球菌和两歧双歧杆菌。为了在肠道中实现位点特异性释放,EcN被设计成表达角化酶(EcNker),使水凝胶在肠道中降解。在葡聚糖硫酸钠诱导的结肠炎模型小鼠中,水凝胶包封EcNker的治疗效果明显优于未包封的益生菌,表现为临床症状的改善、结肠组织学的恢复、肠道细胞凋亡的减少和炎症细胞因子的正常化。从机制上讲,水凝胶包封的EcNker处理通过上调紧密连接蛋白水平,通过增加有益菌的数量来调节肠道微生物群,并增加短链脂肪酸的产生来恢复肠道屏障的完整性。总的来说,我们的研究结果强调了角蛋白水凝胶作为口服工程益生菌治疗结肠结肠炎和其他疾病的通用生物相容性和高效递送平台的潜力。
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引用次数: 0
3D Printable Ethylene-co-vinyl Acetate-Hydroxyapatite Composites for Bone Substitute Applications 用于骨替代品应用的3D打印乙烯-醋酸乙烯-羟基磷灰石复合材料。
IF 4.7 Q2 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-12 DOI: 10.1021/acsabm.5c01291
Athira Murali, , , Shiny Velayudhan, , , Prakash Nair, , and , Ramesh Parameswaran*, 

Over the years, 3D printing has become a multidisciplinary research hotspot and state-of-the-art technology for developing bioinspired structures with intricate geometry, mechanical robustness and verified designs. However, the extrusion complexity of thermoplastic elastomeric filaments makes it challenging to design complex shapes in filament-based extrusion 3D printing. Herein, the paucity of low-modulus ethylene-co-vinyl acetate (EVA) polymer for the fabrication of bone tissue mimetic scaffolds was addressed by compounding with hydroxyapatite (HAP) and the effects of HAP incorporation on extrudability, printability, mechanical properties and osteoblast–material interactions were studied. The systematic optimization of printability and printing parameters enabled successful 3D printing of composite scaffolds with controlled deposition, pore geometry and architecture using a pellet-extrusion 3D printer. The die swell, unstable extrudate deposition and warpage of the EVA polymer melt subsided upon HAP addition. Confocal Raman microscopy and scanning electron microscopy (SEM) confirmed the uniform dispersion of HAP in EVA matrix, necessary to yield stable extrusion of the polymer melt. Dynamic mechanical analysis (DMA) revealed a 5-fold increase in storage modulus as well as a shift in Tg of the composites from −13°C to −9.8°C for 40 vol % HAP, confirming the possible polymer-HAP interactions. Biocompatibility studies demonstrated robust viability, proliferation and cellular integrity, especially in scaffolds with 40 vol % HAP. Moreover, F-actin staining of MG-63 cells revealed expanded cell pseudopods distributed evenly across the scaffold surface with a polygonal spreading pattern, confirming the cell adhesion and proliferation conducive for osteogenesis on the composite scaffolds. Osteogenic differentiation, as evidenced by ALP activity and Alizarin red S staining, indicated statistically higher levels of osteogenic-related factors and mineralization in composite scaffolds relative to neat EVA. These primary findings collectively support that the EVA-HAP composite, especially with 40 vol % HAP loading, provides a suitable microenvironment for osteoblast activities and is expected to promote bone tissue formation.

多年来,3D打印已经成为一个多学科的研究热点和最先进的技术,用于开发具有复杂几何形状,机械稳健性和验证设计的仿生结构。然而,热塑性弹性体长丝的挤压复杂性使得在基于长丝的挤压3D打印中设计复杂形状具有挑战性。本文通过与羟基磷灰石(HAP)复配,解决了制备模拟骨组织支架用低模量EVA聚合物的缺乏问题,并研究了HAP掺入对其可挤压性、可打印性、力学性能和成骨材料相互作用的影响。系统优化了可打印性和打印参数,使用颗粒挤压3D打印机成功打印出具有可控沉积、孔隙几何形状和结构的复合材料支架。添加HAP后,EVA聚合物熔体的模胀、不稳定的挤出物沉积和翘曲现象得到缓解。共聚焦拉曼显微镜和扫描电镜(SEM)证实了HAP在EVA基体中的均匀分散,这是聚合物熔体稳定挤出所必需的。动态力学分析(DMA)显示,当HAP含量为40 vol %时,复合材料的存储模量增加了5倍,Tg从-13°C变为-9.8°C,证实了聚合物-HAP之间可能存在相互作用。生物相容性研究显示了强大的活力,增殖和细胞完整性,特别是在40 vol % HAP的支架中。此外,MG-63细胞的F-actin染色显示扩增的细胞假足均匀分布在支架表面,呈多边形扩散模式,证实了细胞在复合支架上的粘附和增殖有利于成骨。ALP活性和茜素红S染色表明,与纯EVA相比,复合支架的成骨相关因子和矿化水平在统计学上更高。这些初步发现共同支持EVA-HAP复合材料,特别是40 vol % HAP负载,为成骨细胞活动提供了合适的微环境,并有望促进骨组织形成。
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