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Non-invasive transdermal delivery of peptide inhibitors of the IL-23/IL-17 axis by novel ionic liquid biomaterials for psoriasis treatment 新型离子液体生物材料无创经皮递送IL-23/IL-17轴肽抑制剂治疗银屑病
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-28 DOI: 10.1039/D5BM01168J
Xiaolei Ma, Zun Wang, Mihribangvl Alip, Qi Mao, Cheng Zhao, Huayong Zhang, Genhong Yao, Lingyun Sun and Lei Jiang

Psoriasis has been successfully treated by directly blocking the interleukin (IL)-23/IL-17 pathway and several inhibitors that specifically target the IL-23/IL-17 signaling axis have been approved by the Food and Drug Administration for clinical use and show excellent efficacy. However, all the approved IL-23/IL-17 axis targeting agents cannot be non-invasively delivered as topical treatment due to their biological and physicochemical properties, e.g., susceptibility to degradation, large molecular size, hydrophobicity and charge. Herein, we used novel ionic liquid biomaterials, amino acid esters and octanoic acids, as a non-invasive transdermal drug delivery system for bicyclic peptide inhibitors targeted to IL-23R and IL-17A. Using phenotypical images, psoriasis area and severity index, hematoxylin–eosin, and immunohistochemistry, we demonstrate that a biocompatible ionic liquid-based topical delivery approach of peptide inhibitors alleviates psoriasis in an imiquimod-induced psoriasis mouse model. Flow cytometry of innate lymphoid cells (ILCs) within the spleen, peripheral blood, and lesional epidermis shows that treatment with ionic liquids-peptides selectively blocks and reconfigures the spectrum of skin-resident and circulating ILCs. These results provide a framework for a topical delivery approach for peptides. Our findings highlight the potential of topical administration of peptide inhibitors of the IL-23/IL-17 pathway by biocompatible ionic liquids to treat psoriasis. The main immunopathogenic mechanism of peptide inhibitors mitigating psoriasis is reconfiguration of a spectrum of skin-resident and circulating ILCs.

直接阻断白介素(IL)-23/IL-17通路已成功治疗银屑病,几种特异性靶向IL-23/IL-17信号轴的抑制剂已被美国食品和药物管理局批准临床使用,并显示出优异的疗效。然而,所有被批准的IL-23/IL-17轴靶向药物由于其生物和物理化学性质,如易降解、大分子尺寸、疏水性和电荷性,不能作为局部治疗无创伤递送。本研究采用新型离子液体生物材料氨基酸酯和辛酸作为靶向IL-23R和IL-17A的双环肽抑制剂的无创透皮给药系统。利用表型图像、牛皮癣面积和严重程度指数、苏木精-伊红和免疫组织化学,我们证明了一种生物相容性离子液体为基础的肽抑制剂局部递送方法可以缓解吡喹莫德诱导的牛皮癣小鼠模型中的牛皮癣。脾、外周血和病变表皮内的先天淋巴样细胞(ILCs)的流式细胞术显示,离子液体-肽治疗选择性地阻断和重新配置皮肤驻留和循环的ILCs的光谱。这些结果为多肽的局部递送方法提供了一个框架。我们的研究结果强调了通过生物相容性离子液体局部给药IL-23/IL-17途径的肽抑制剂治疗牛皮癣的潜力。肽抑制剂缓解银屑病的主要免疫致病机制是皮肤驻留和循环ILCs谱的重构。
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引用次数: 0
Transformation of nanoparticles into hydrogels for long-acting and sensitized apoptosis therapy of triple negative breast cancer 纳米颗粒转化为水凝胶对三阴性乳腺癌的长效增敏细胞凋亡治疗。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-27 DOI: 10.1039/D5BM01226K
Linna Yu, Jianping Zhou, Hao Cheng and Yang Ding

Despite the high sensitivity of triple-negative breast cancer (TNBC) to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy, its efficacy was limited by rapid systemic clearance and treatment tolerance. To overcome these barriers, we developed a pH-responsive nanoparticle-to-hydrogel system for long-lasting retention of TRAIL receptors at the tumour site and promoting apoptosis in TRAIL-sensitive TNBC cells. The nanoparticle core, composed of soluble TRAIL (sTRAIL) and terpyridine (TPY), was assembled via silk fibroin self-polymerization, while a metal–polyphenol (MPN) complexation structure imparts a pH-responsive outer shell. After peritumoral injection, the slightly acidic tumour microenvironment transiently degraded MPN, releasing dihydromyricetin (DMY) to upregulate the TRAIL receptor DR5, whereas Fe3+ covalently bound TPY, triggering nanoparticle-to-gel conversion. The system achieved a high DMY loading via the MPN network, rapidly released DMY under acidic tumour microenvironment conditions, and induced apoptotic receptor DR5 upregulation within 24 h. Dynamic covalent bond reconstitution converted nanoparticles into a hydrogel in situ, forming a stable library for sustained TRAIL release. Compared with conventional gels, this sequential fast-activation and continuous synergistic apoptosis strategy minimized burst release, extended TRAIL activity beyond six days, and localized the drug to the lesion area, increasing the local concentration of the drug while reducing systemic exposure. In vitro and in vivo studies confirmed enhanced apoptosis through dual-drug synergy with minimal systemic toxicity. This dynamic switching strategy delivery offers an innovative platform for protein–small molecule co-therapy, addressing TNBC resistance, and holds translational potential for clinical applications.

尽管三阴性乳腺癌(TNBC)对肿瘤坏死因子相关凋亡诱导配体(TRAIL)治疗具有高度敏感性,但其疗效受到快速全身清除和治疗耐受性的限制。为了克服这些障碍,我们开发了一种ph响应纳米颗粒-水凝胶系统,用于TRAIL受体在肿瘤部位的长期保留,并促进TRAIL敏感的TNBC细胞的凋亡。由可溶性TRAIL (sTRAIL)和三吡啶(TPY)组成的纳米粒子内核通过丝素蛋白自聚合组装,而金属-多酚(MPN)络合结构赋予了ph响应的外壳。在瘤周注射后,微酸性肿瘤微环境瞬间降解MPN,释放二氢杨梅素(DMY)上调TRAIL受体DR5,而Fe3+共价结合TPY,触发纳米颗粒到凝胶的转化。该系统通过MPN网络实现了高DMY负载,在酸性肿瘤微环境条件下快速释放DMY,并在24 h内诱导凋亡受体DR5上调。动态共价键重构将纳米颗粒原位转化为水凝胶,形成了一个稳定的TRAIL持续释放文库。与传统凝胶相比,这种连续快速激活和持续协同凋亡策略最大限度地减少了爆发释放,将TRAIL活性延长至6天以上,并将药物定位于病变区域,增加了药物的局部浓度,同时减少了全身暴露。体外和体内研究证实,通过双药协同作用增强细胞凋亡,并且具有最小的全身毒性。这种动态转换策略提供了一个创新的蛋白质-小分子联合治疗平台,解决TNBC耐药问题,并具有临床应用的转化潜力。
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引用次数: 0
Red blood cell-derived extracellular vesicles as biomaterials: the opportunity of freezing-induced accelerated aging 红细胞来源的细胞外囊泡作为生物材料:冷冻诱导加速衰老的机会。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-25 DOI: 10.1039/D5BM01349F
Lucia Paolini, Miriam Romano, Valentina Mangolini, Selene Tassoni, Shuhan Jiang, Elena Laura Mazzoldi, Angelo Musicò, Andrea Zendrini, Anna Kashkanova, Vahid Sandoghdar, Anna C. Berardi, Silvia Clara Giliani, Paolo Bergese and Annalisa Radeghieri

Red blood cell-derived extracellular vesicles (RBC-EVs) are emerging as promising biomaterials for next-generation drug delivery, owing to their intrinsic biocompatibility, immune-evasion properties, and minimal oncogenic risk. However, their broader application is currently limited by unresolved challenges related to heterogeneity, reproducibility, and long-term storage stability. By combining discontinuous sucrose density gradient separation with high-resolution interferometric nanoparticle tracking analysis, we identified a sharp bimodal size distribution of vesicles in freshly prepared samples. We then tracked how long-term storage at −80 °C drove their conversion into a monomodal distribution. To reproduce these conditions in a shorter time frame, we developed an “accelerated-ageing” protocol based on freeze–thaw cycles that generates RBC-EV samples with homogeneous density, size distribution, and biological activity, effectively replicating the properties of preparations stored for six months at −80 °C. This new vesicle population remains stable and retains membrane integrity and cellular internalization capacity, as confirmed by surface-associated enzymatic activity assays and uptake tests in cancer cell lines. These results suggest that freezing-induced “accelerated ageing” represents an effective method for the optimization and standardization of RBC-EVs as building blocks for biomaterial and bioengineering applications.

红细胞来源的细胞外囊泡(红细胞外囊泡)由于其固有的生物相容性、免疫逃避特性和最小的致癌风险,正在成为下一代药物输送的有前途的生物材料。然而,它们的广泛应用目前受到与异质性、可重复性和长期存储稳定性相关的未解决的挑战的限制。通过将不连续蔗糖密度梯度分离与高分辨率干涉纳米颗粒跟踪分析相结合,我们在新制备的样品中发现了一个尖锐的双峰大小分布的囊泡。然后,我们追踪了在-80°C的长期储存是如何将它们转化为单模态分布的。为了在更短的时间内重现这些条件,我们开发了一种基于冻融循环的“加速老化”方案,该方案生成的RBC-EV样品具有均匀的密度、大小分布和生物活性,有效地复制了在-80°C下储存6个月的制剂的特性。癌细胞的表面相关酶活性测定和摄取试验证实,这种新的囊泡群保持稳定,并保持膜完整性和细胞内化能力。这些结果表明,冷冻诱导的“加速老化”是优化和标准化红细胞ev作为生物材料和生物工程应用基础的有效方法。
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引用次数: 0
Nanoarchitectured molybdenum oxide nanozymes: from fabrication strategies to theranostic application 纳米结构氧化钼纳米酶:从制造策略到治疗应用。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-24 DOI: 10.1039/D5BM01362C
Xuehui Zhu, Jinghua Li, Yanfei Liang, Zeng Yang, Jing Fu and Aihua Li

Nanoarchitectured molybdenum oxides (MoOx) have emerged as promising artificial enzymes, capable of mimicking a broad range of enzymatic activities, including oxidase, peroxidase, catalase, and sulfite oxidase, owing to their unique physicochemical properties such as variable oxidation states, tunable electronic structures, and pH-responsive biodegradability. In addition, MoOx-based systems demonstrate strong photoresponsiveness, enabling the synergistic integration of enzymatic catalysis with photothermal (PTT) or photodynamic (PDT) therapies under near-infrared (NIR) irradiation. Their excellent biocompatibility and biodegradability further highlight their potential for biomedical applications. This review provides a comprehensive overview of recent advances in the design, synthesis, and bioapplications of MoOx nanozymes, with an emphasis on their structural versatility and multifunctional therapeutic capabilities. Through strategies such as defect engineering, surface functionalization, and heteroatom doping, the enzyme-mimicking activities of MoOx nanozymes can be finely tuned, enabling outstanding performance in biosensing, antitumor and antimicrobial therapies, and antioxidation. Finally, the review outlines the prospects and key challenges in translating these innovative nanoplatforms into clinical applications.

纳米结构的钼氧化物(MoOx)由于其独特的物理化学性质,如可变氧化态、可调电子结构和ph响应性,能够模拟广泛的酶活性,包括氧化酶、过氧化物酶、过氧化氢酶和亚硫酸盐氧化酶,已经成为一种有前途的人工酶。此外,基于moox的系统表现出很强的光响应性,可以在近红外(NIR)照射下将酶催化与光热(PTT)或光动力(PDT)疗法协同整合。其优异的生物相容性和生物降解性进一步凸显了其生物医学应用的潜力。本文综述了MoOx纳米酶的设计、合成和生物应用方面的最新进展,重点介绍了MoOx纳米酶的结构通用性和多功能治疗能力。通过缺陷工程、表面功能化和杂原子掺杂等策略,MoOx纳米酶的酶模拟活性可以被精细调节,从而在生物传感、抗肿瘤和抗菌治疗以及抗氧化方面具有出色的性能。最后,综述概述了将这些创新纳米平台转化为临床应用的前景和主要挑战。
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引用次数: 0
Correction: Artificial testis: a testicular tissue extracellular matrix as a potential bio-ink for 3D printing 修正:人工睾丸:睾丸组织细胞外基质作为3D打印的潜在生物墨水。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-24 DOI: 10.1039/D5BM90090E
Zahra Bashiri, Iraj Amiri, Mazaher Gholipourmalekabadi, Reza Falak, Hamidreza Asgari, Chad B. Maki, Ali Moghaddaszadeh and Morteza Koruji

Correction for ‘Artificial testis: a testicular tissue extracellular matrix as a potential bio-ink for 3D printing’ by Zahra Bashiri et al., Biomater. Sci., 2021, 9, 3465–3484, https://doi.org/10.1039/D0BM02209H.

更正“人造睾丸:睾丸组织细胞外基质作为3D打印的潜在生物墨水”,作者:Zahra Bashiri等人,Biomater。科学。, 2021, 9, 3465-3484, https://doi.org/10.1039/D0BM02209H。
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引用次数: 0
Bionic gradient scaffolds for osteochondral tissue engineering: construction strategies, interface optimization, gradient characterization, and controllability research 骨软骨组织工程仿生梯度支架:构建策略、界面优化、梯度表征及可控性研究。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-24 DOI: 10.1039/D5BM01230A
Fufen Li, Xiaohan Yang, Yining Chen, Min Gong, Lang Li, Anjing Chen, Nianhua Dan and Zhengjun Li

Osteochondral (OC) tissue faces significant challenges in defect repair due to its unique gradient characteristics. Bionic gradient scaffolds have been developed to address this issue, whose anisotropic three-dimensional structures can achieve gradual transitions in physical and chemical properties, providing innovative solutions for tissue regeneration. This review first focuses on the multidimensional gradient characteristics of natural OC tissue, including its composition, structure, performance, and metabolism, and provides an in-depth discussion of its significance for the design of biomimetic scaffolds. Second, it summarizes the current research progress on the construction strategy of gradient scaffolds. On this basis, this review innovatively proposes a systematic interface optimization strategy for discrete gradient scaffolds and summarizes the latest research progress on the gradient characterization and controllability of continuous gradient scaffolds. Finally, based on the current advances of research, this paper evaluates the main challenges facing this field and reviews the prospects in future development directions, providing new theoretical perspectives and technical routes for OC tissue engineering research.

骨软骨组织由于其独特的梯度特性,在缺陷修复中面临着巨大的挑战。仿生梯度支架的发展就是为了解决这一问题,其各向异性的三维结构可以实现物理和化学性质的逐渐转变,为组织再生提供了创新的解决方案。本文首先对天然OC组织的组成、结构、性能、代谢等多维梯度特征进行了综述,并对其对仿生支架设计的意义进行了深入探讨。其次,综述了目前梯度支架构建策略的研究进展。在此基础上,本文创新性地提出了离散梯度支架的系统界面优化策略,并对连续梯度支架的梯度表征和可控性的最新研究进展进行了总结。最后,根据目前的研究进展,对该领域面临的主要挑战进行了评价,并对未来发展方向进行了展望,为OC组织工程研究提供了新的理论视角和技术路线。
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引用次数: 0
Does mechanobiology drive respiratory disease? Biomechanical induction of mucus hypersecretion in human bronchial organoids using a photocontrolled biomaterial gel 机械生物学导致呼吸系统疾病吗?利用光控生物材料凝胶生物力学诱导人支气管类器官粘液高分泌。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-20 DOI: 10.1039/D5BM00958H
Isabel E. Uwagboe, Sharon Mumby, Iain E. Dunlop and Ian M. Adcock

Respiratory diseases such as COPD, IPF and severe asthma are major causes of death globally, characterized by chronic inflammation and by fibrotic biomechanical remodelling of the lung ECM. However, present treatments focus on relieving inflammation and symptoms and do not address the mechanobiological aspect. This is in great part because the role of mechanobiology in disease progression and aetiology is not well-understood, indicating a need for new investigatory models. Here we introduce a combined biomaterial and 3D-organoid model, based on a hybrid biomaterial-matrix double-network gel, whose mechanical properties are dynamically photocontrolled by the application of light. This combines basement membrane extract (Matrigel) with biocompatible polymer (poly(ethylene glycol)diacrylate), and a low-toxicity photoinitation system. We achieve rapid (<5 min) photoinduced stiffening over the range of remodelled lung tissue (up to ∼140 kPa). Bronchosphere organoids from primary human bronchial epithelial cells, embedded within the hybrid gel, replicate airway physiology and exhibit a dynamic biological response to matrix stiffening. We show that the expression of mucus proteins MUC5AC and MUC5B is biomechanically enhanced over a period of 24–72 h, with in particular MUC5B showing a substantial response at 48 h after matrix stiffening. Mucus hypersecretion is a symptom of respiratory disease, and these results support the hypothesis that biomechanics is a driver of disease aetiology. We combine the photostiffened hybrid matrix gel with organoids from COPD donors, generating an advanced disease model including both cellular and biomechanical aspects. We propose this technology platform for evaluating mechanomodulatory therapeutics in respiratory disease.

慢性阻塞性肺病、IPF和严重哮喘等呼吸系统疾病是全球死亡的主要原因,其特征是慢性炎症和肺外膜纤维化生物力学重构。然而,目前的治疗侧重于缓解炎症和症状,而不是解决机械生物学方面。这在很大程度上是因为机械生物学在疾病进展和病因学中的作用尚未得到很好的理解,这表明需要新的研究模型。在这里,我们介绍了一种基于混合生物材料-基质双网络凝胶的生物材料和3d类器官模型,其力学性能通过光的应用动态光控制。它结合了基膜提取物(Matrigel)和生物相容性聚合物(聚乙二醇二丙烯酸酯),以及低毒的光引发系统。我们实现了快速(
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引用次数: 0
4D bioprinting of protein-based bioinks for tissue engineering and disease models 用于组织工程和疾病模型的蛋白质基生物墨水的4D生物打印。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-18 DOI: 10.1039/D5BM01284H
Yusuf Olatunji Waidi and Sriram Bharath Gugulothu

Four-dimensional (4D) printing enables the creation of dynamic structures that can change, altering their shape, properties, or functionality in response to stimuli over time by incorporating time as a fourth dimension. This revolutionary approach has gotten significant attention across various fields, with recent advancements in integrating smart biomaterials, biological components, and living cells into dynamic, three-dimensional (3D) constructs. Among the myriad of biomaterials available, protein-based (PB) polymers have emerged as promising due to their inherent biocompatibility, biodegradability, and ability to interact with and mimic the extracellular matrix (ECM). This review provides a comprehensive overview of 4D bioprinting, involving PB bioinks, and explores key principles, mechanisms, strategies, and types. It discusses essential requirements, such as printability, biodegradation, and mechanical integrity, as well as strategies for designing stimuli-responsive 4D bioinks. Furthermore, it comprehensively explores emerging trends in applying these bioinks for the 4D bioprinting of tissue scaffolds and their utility in disease modeling. Finally, it addresses current challenges and prospects, aiming to provide readers with a thorough understanding of recent developments in this groundbreaking technology towards adaptability in regenerative medicine and disease models.

四维(4D)打印可以创建动态结构,随着时间的推移,通过将时间作为第四个维度,可以改变其形状,属性或功能,以响应刺激。这种革命性的方法已经在各个领域引起了极大的关注,最近在将智能生物材料、生物成分和活细胞集成到动态的三维(3D)结构中取得了进展。在众多可用的生物材料中,基于蛋白质(PB)的聚合物由于其固有的生物相容性、生物可降解性以及与细胞外基质(ECM)相互作用和模拟的能力而变得很有前途。本文综述了包括PB生物墨水在内的4D生物打印技术,并探讨了4D生物打印的主要原理、机制、策略和类型。它讨论了基本要求,如可打印性,生物降解和机械完整性,以及设计刺激响应4D生物墨水的策略。此外,它还全面探讨了将这些生物墨水应用于组织支架的4D生物打印及其在疾病建模中的应用的新兴趋势。最后,它解决了当前的挑战和前景,旨在为读者提供对再生医学和疾病模型适应性这一突破性技术的最新发展的透彻理解。
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引用次数: 0
Correction: TPP-coated Mo-doped W18O49 biodegradable nanomaterials with mitochondria-targeting and pH-responsive properties for synergistic photothermal therapy/chemodynamic therapy/chemotherapy 校正:tpp包被的mo掺杂W18O49可生物降解纳米材料,具有线粒体靶向和ph响应特性,用于协同光热治疗/化学动力学治疗/化疗。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-17 DOI: 10.1039/D5BM90089A
Yingjuan Ren, Wenhui Yi, Jie Gao, Nan Wang and Di Zhuang

Correction for ‘TPP-coated Mo-doped W18O49 biodegradable nanomaterials with mitochondria-targeting and pH-responsive properties for synergistic photothermal therapy/chemodynamic therapy/chemotherapy’ by Yingjuan Ren et al., Biomater. Sci., 2025, 13, 6138–6155, https://doi.org/10.1039/D5BM00833F.

对“具有线粒体靶向和ph响应特性的tpp包被掺杂mo的W18O49可生物降解纳米材料,用于协同光热治疗/化学动力治疗/化疗”的修正(任英娟等人,Biomater)。科学。生态学报,2025,13,6138-6155,https://doi.org/10.1039/D5BM00833F。
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引用次数: 0
Catechol modification as a platform for functional coatings 儿茶酚改性作为功能涂料的平台。
IF 5.7 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-17 DOI: 10.1039/D5BM01363A
Banibrata Maiti, Erik V. Van der Eycken and Guglielmo A. Coppola

Catechol-based surface functionalization has emerged as a powerful strategy for tailoring material properties and enabling diverse applications, owing to its robust adhesive capabilities and broad substrate compatibility. Inspired by mussel foot proteins and popularized by dopamine-derived polydopamine coatings, catechol grafting has evolved into a versatile platform for anchoring molecules of interest (MOI) onto surfaces. This review focuses on the synthetic strategies for direct covalent modification of active compounds—such as polymers, peptides, and small molecules—with catechol moieties, bypassing the limitations of traditional bottom-up and co-deposition approaches. By examining the reactivity profiles of catechol precursors and their coupling chemistries, we aim to provide a comprehensive framework for designing functional coatings with enhanced performance and simplified processing. This work fills a critical gap in the literature by offering practical guidelines for researchers seeking to harness catechol chemistry in advanced material engineering.

由于其强大的粘合能力和广泛的基材兼容性,基于儿茶酚的表面功能化已成为定制材料特性和实现多种应用的强大策略。受贻贝足蛋白的启发,并由多巴胺衍生的聚多巴胺涂层推广,儿茶酚接枝已经发展成为一种将感兴趣分子(MOI)锚定在表面上的多功能平台。本文综述了利用儿茶酚基团对活性化合物(如聚合物、多肽和小分子)进行直接共价修饰的合成策略,绕过了传统自下而上和共沉积方法的局限性。通过研究儿茶酚前体及其偶联化学的反应性,我们的目标是为设计具有增强性能和简化工艺的功能涂层提供一个全面的框架。这项工作填补了文献中的一个关键空白,为寻求在先进材料工程中利用儿茶酚化学的研究人员提供了实用指南。
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引用次数: 0
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