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Development of a 3D printed perfusable in vitro blood-brain barrier model for use as a scalable screening tool. 开发三维打印可灌注体外血脑屏障模型,用作可扩展的筛选工具。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-07-18 DOI: 10.1039/d4bm00663a
Madison K Royse, Martha Fowler, A Kristen Mai, Yufang He, Marc R Durante, Nicole Buist, Adam Procopio, Jun Xu, Omid Veiseh

Despite recent technological advances in drug discovery, the success rate for neurotherapeutics remains alarmingly low compared to treatments for other areas of the body. One of the biggest challenges for delivering therapeutics to the central nervous system (CNS) is the presence of the blood-brain barrier (BBB). In vitro blood-brain barrier models with high predictability are essential to aid in designing parameters for new therapeutics, assess their ability to cross the BBB, and investigate therapeutic strategies that can be employed to enhance transport. Here, we demonstrate the development of a 3D printable hydrogel blood-brain barrier model that mimics the cellular composition and structure of the blood-brain barrier with human brain endothelial cells lining the surface, pericytes in direct contact with the endothelial cells on the abluminal side of the endothelium, and astrocytes in the surrounding printed bulk matrix. We introduce a simple, static printed hemi-cylinder model to determine design parameters such as media selection, co-culture ratios, and cell incorporation timing in a resource-conservative and high-throughput manner. Presence of cellular adhesion junction, VE-Cadherin, efflux transporters, P-glycoprotein (P-gp) and Breast cancer resistance protein (BCRP), and receptor-mediated transporters, Transferrin receptor (TfR) and low-density lipoprotein receptor-related protein 1 (LRP1) were confirmed via immunostaining demonstrating the ability of this model for screening in therapeutic strategies that rely on these transport systems. Design parameters determined in the hemi-cylinder model were translated to a more complex, perfusable vessel model to demonstrate its utility for determining barrier function and assessing permeability to model therapeutic compounds. This 3D-printed blood-brain barrier model represents one of the first uses of projection stereolithography to fabricate a perfusable blood-brain barrier model, enabling the patterning of complex vessel geometries and precise arrangement of cell populations. This model demonstrates potential as a new platform to investigate the delivery of neurotherapeutic compounds and drug delivery strategies through the blood-brain barrier, providing a useful in vitro screening tool in central nervous system drug discovery and development.

尽管最近在药物发现方面取得了技术进步,但与身体其他部位的治疗相比,神经治疗的成功率仍然低得惊人。向中枢神经系统(CNS)输送治疗药物的最大挑战之一是血脑屏障(BBB)的存在。具有高度可预测性的体外血脑屏障模型对于帮助设计新疗法的参数、评估其穿越血脑屏障的能力以及研究可用于增强转运的治疗策略至关重要。在这里,我们展示了三维可打印水凝胶血脑屏障模型的开发过程,该模型模仿了血脑屏障的细胞组成和结构,其表面衬有人脑内皮细胞,内皮细胞背面的周细胞与内皮细胞直接接触,星形胶质细胞则位于周围的打印体基质中。我们引入了一个简单的静态印刷半圆柱体模型,以资源节约和高通量的方式确定设计参数,如培养基选择、共培养比例和细胞加入时间。通过免疫染色法确认了细胞粘附连接蛋白 VE-Cadherin、外排转运体 P-glycoprotein (P-gp) 和乳腺癌抗性蛋白 (BCRP),以及受体介导转运体转铁蛋白受体 (TfR) 和低密度脂蛋白受体相关蛋白 1 (LRP1)的存在,这表明该模型能够筛选依赖于这些转运系统的治疗策略。在半圆柱体模型中确定的设计参数被转化为更复杂的可灌注血管模型,以证明其在确定屏障功能和评估对模型治疗化合物的渗透性方面的实用性。这种三维打印的血脑屏障模型是首次使用投影立体光刻技术制造可灌注血脑屏障模型的技术之一,可实现复杂血管几何形状的图案化和细胞群的精确排列。该模型展示了作为研究通过血脑屏障输送神经治疗化合物和给药策略的新平台的潜力,为中枢神经系统药物的发现和开发提供了有用的体外筛选工具。
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引用次数: 0
Medical and molecular biophysical techniques as substantial tools in the era of mRNA-based vaccine technology. 医学和分子生物物理学技术是基于 mRNA 的疫苗技术时代的重要工具。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-07-17 DOI: 10.1039/d4bm00561a
Abid Hussain, Maoye Wang, Dan Yu, Jiahui Zhang, Qais Ahmad Naseer, Aftab Ullah, Julien Milon Essola, Xu Zhang

The COVID-19 pandemic prompted the advancement of vaccine technology using mRNA delivery into the host cells. Consequently, mRNA-based vaccines have emerged as a practical approach against SARS-CoV-2 owing to their inherent properties, such as cost-effectiveness, rapid manufacturing, and preservation. These features are vital, especially in resource-constrained regions. Nevertheless, the design of mRNA-based vaccines is intricately intertwined with the refinement of biophysical technologies, thereby establishing their high potential. The preparation of mRNA-based vaccines involves a sequence of phases combining medical and molecular biophysical technologies. Furthermore, their efficiency depends on the capability to optimize their positive attributes, thus paving the way for their subsequent preclinical and clinical evaluations. Using biophysical techniques, the characterization of nucleic acids extends from their initial formulation to their cellular internalization abilities and encapsulation in biomolecule complexes, such as lipid nanoparticles (LNPs), for designing mRNA-based LNPs. Furthermore, nanoparticles are subjected to a series of careful screening steps to assess their physical and chemical characteristics before achieving an optimum formulation suitable for preclinical and clinical studies. This review provides a comprehensive understanding of the fundamental role of biophysical techniques in the complex development of mRNA-based vaccines and their role in the recent success during the COVID-19 pandemic.

COVID-19 大流行推动了利用 mRNA 向宿主细胞递送疫苗技术的发展。因此,基于 mRNA 的疫苗因其固有的特性,如成本效益、快速制造和保存等,已成为抗击 SARS-CoV-2 的实用方法。这些特性至关重要,尤其是在资源有限的地区。尽管如此,基于 mRNA 的疫苗的设计与生物物理技术的完善密切相关,因此其潜力巨大。制备基于 mRNA 的疫苗涉及一系列结合医学和分子生物物理技术的阶段。此外,疫苗的效率取决于优化其积极属性的能力,从而为后续的临床前和临床评估铺平道路。使用生物物理技术,核酸的表征范围从最初的配制扩展到细胞内化能力以及在生物大分子复合物(如脂质纳米粒子(LNPs))中的封装,以设计基于 mRNA 的 LNPs。此外,在获得适合临床前和临床研究的最佳配方之前,还要对纳米颗粒进行一系列仔细的筛选步骤,以评估其物理和化学特性。这篇综述全面介绍了生物物理技术在基于 mRNA 的疫苗的复杂开发过程中所起的基本作用,以及它们在最近 COVID-19 大流行期间所起的成功作用。
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引用次数: 0
Halogen Atom Regulation of Acceptor-Donor-Acceptor Type Conjugated Molecules for Photothermal Antibacterial and Antibiofilm Therapy 用于光热抗菌和抗生物膜疗法的受体-捐献者-受体型共轭分子的卤原子调控技术
IF 6.6 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-07-17 DOI: 10.1039/d4bm00605d
Yue Zhao, Yuanyuan Cui, Shijie Xie, Ruilian Qi, Li Xu, Huanxiang Yuan
Drug-resistant bacteria and biofilm have caused serious public health problems. It is necessary to develop a treatment that is highly effective against drug-resistant bacteria without inducing drug resistance. Herein, we prepare a series of nanoparticles based on three conjugated molecules (BTP-BrCl, BTP-ClBr, and BTP-ClmBr) with acceptor-donor-acceptor (A-D-A) structure. By adjusting the position of the halogen atoms, the photothermal properties can be effectively regulated. In particular, these three nanoparticles (BTP-BrCl, BTP-ClBr, and BTP-ClmBr NPs) exhibited photothermal conversion efficiencies (PCE) up to 57.4%, 60.3%, and 75.9%, respectively. Among these nanoparticles, BTP-ClmBr NPs with the chlorine atom close to the carbonyl and bromine atom away from the carbonyl in the acceptor have the highest PCE. Due to their excellent photothermal properties, all the NPs achieved more than 99.9% antibacterial activity against Ampr E. coli, S. aureus and MRSA. When S. aureus was treated with these three nanoparticles under light irradiation, little biofilm formation was observed. Moreover, they could kill more than 99.9% of the bacteria in the biofilm. In summary, this study provides a strategy for the preparation of high-performance nano-photothermal agents and their application in the field of anti-drug resistant bacteria and biofilm prevention and cure.
耐药细菌和生物膜已造成严重的公共卫生问题。有必要开发出一种既能高效杀灭耐药细菌,又不会诱发耐药性的治疗方法。在此,我们以三种共轭分子(BTP-BrCl、BTP-ClBr 和 BTP-ClmBr)为基础,制备了一系列具有受体-供体-受体(A-D-A)结构的纳米粒子。通过调整卤素原子的位置,可以有效调节光热特性。其中,这三种纳米粒子(BTP-BrCl、BTP-ClBr 和 BTP-ClmBr NPs)的光热转换效率(PCE)分别高达 57.4%、60.3% 和 75.9%。在这些纳米粒子中,受体中氯原子靠近羰基、溴原子远离羰基的 BTP-ClmBr NPs 的 PCE 最高。由于其出色的光热特性,所有 NPs 对 Ampr 大肠杆菌、金黄色葡萄球菌和 MRSA 的抗菌活性都超过了 99.9%。在光照射下用这三种纳米粒子处理金黄色葡萄球菌时,几乎没有观察到生物膜的形成。此外,它们还能杀死生物膜中 99.9% 以上的细菌。总之,本研究为制备高性能纳米光热剂及其在抗耐药菌和生物膜防治领域的应用提供了一种策略。
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引用次数: 0
Comparative analysis of aligned and random amniotic membrane-derived cryogels for neural tissue repair 用于神经组织修复的对齐羊膜和随机羊膜低温凝胶的比较分析
IF 6.6 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-07-17 DOI: 10.1039/d4bm00364k
Joana P. M. Sousa, Inês Deus, Cátia Monteiro, Catarina Custodio, Emmanuel Stratakis, João F. Mano, Paula Marques
The ordered arrangement of cells and extracellular matrix facilitates the seamless transmission of electrical signals along axons in the spinal cord and peripheral nerves. Therefore, restoring tissue geometry is crucial for neural regeneration. This study presents a novel method using proteins derived from the human amniotic membrane, which is modified with photoresponsive groups, to produce cryogels with aligned porosity. Freeze-casting was used to produce cryogels with longitudinally aligned pores, while cryogels with randomly distributed porosity were used as control. The cryogels exhibited remarkable injectability and shape recovery properties, essential for minimally invasive applications. Different tendencies in proliferation and differentiation were evident between aligned and random cryogels, underscoring the significance of the scaffold's microstructure in directing neural stem cells’ (NSC) behaviour. Remarkably, aligned cryogels facilitated extensive cellular infiltration and migration, contrasting with NSC cultured on isotropic cryogels, which predominantly remained on the scaffold's surface throughout the proliferation experiment. Significantly, the proliferation assay demonstrated that on day 7, the aligned cryogels contained eight times more cells compared to the random cryogels. Consistent with the proliferation experiments, NSC exhibited the ability to differentiate into neurons within the aligned scaffolds and extending neurites longitudinally. In addition, differentiation assays showed a four-fold increase in the expression of neural markers in the cross-sections of the aligned cryogels. Conversely, the random cryogels exhibited minimal presence of cell bodies and extensions. The presence of synaptic vesicles on the anisotropic cryogels indicates the formation of functional synaptic connections, emphasizing the importance of the scaffold's microstructure in guiding neuronal reconnection.
细胞和细胞外基质的有序排列有助于脊髓和周围神经轴突电信号的无缝传输。因此,恢复组织的几何形状对神经再生至关重要。本研究提出了一种新方法,利用从人类羊膜中提取的蛋白质,经过光致伸缩基团修饰,生产出具有排列有序的孔隙率的冷凝胶。冷冻铸造法用于生产纵向排列孔隙的冷凝胶,而随机分布孔隙的冷凝胶则作为对照。低温凝胶具有显著的可注射性和形状恢复特性,这对微创应用至关重要。排列和随机低温凝胶的增殖和分化趋势明显不同,这凸显了支架微结构在引导神经干细胞(NSC)行为方面的重要性。值得注意的是,排列整齐的低温凝胶促进了广泛的细胞浸润和迁移,这与在各向同性低温凝胶上培养的神经干细胞形成鲜明对比,后者在整个增殖实验中主要停留在支架表面。值得注意的是,增殖实验表明,在第 7 天,排列整齐的低温凝胶中的细胞数量是随机低温凝胶的八倍。与增殖实验相一致的是,NSC 表现出了在对齐支架内分化成神经元并纵向延伸神经元的能力。此外,分化实验显示,排列整齐的低温凝胶横截面上的神经标记表达量增加了四倍。相反,随机冷凝凝胶则显示出极少的细胞体和延伸。各向异性低温凝胶上突触囊泡的存在表明功能性突触连接的形成,强调了支架微结构在引导神经元重新连接方面的重要性。
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引用次数: 0
Advances in H2O2-supplying materials for tumor therapy: synthesis, classification, mechanisms, and applications. 用于肿瘤治疗的 H2O2- 供给材料的研究进展:合成、分类、机制和应用。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-07-16 DOI: 10.1039/d4bm00366g
Xu Zhang, Mao Li, Ya-Ling Tang, Min Zheng, Xin-Hua Liang

Hydrogen peroxide (H2O2) as a reactive oxygen species produced by cellular metabolism can be used in antitumor therapy. However, the concentration of intracellular H2O2 limits its application. Some materials could enhance the concentration of intracellular H2O2 to strengthen antitumor therapy. In this review, the recent advances in H2O2-supplying materials in terms of promoting intracellular H2O2 production and exogenous H2O2 supply are summarized. Then the mechanism of H2O2-supplying materials for tumor therapy is discussed from three aspects: reconstruction of the tumor hypoxia microenvironment, enhancement of oxidative stress, and the intrinsic anti-tumor ability of H2O2-supplying materials. In addition, the application of H2O2-supplying materials for tumor therapy is discussed. Finally, the future of H2O2-supplying materials is presented. This review aims to provide a novel idea for the application of H2O2-supplying materials in tumor therapy.

过氧化氢(H2O2)是细胞代谢产生的活性氧,可用于抗肿瘤治疗。然而,细胞内 H2O2 的浓度限制了它的应用。一些材料可以提高细胞内 H2O2 的浓度,从而加强抗肿瘤治疗。本综述从促进细胞内 H2O2 生成和外源 H2O2 供给两个方面总结了 H2O2 供给材料的最新进展。然后,从重建肿瘤缺氧微环境、增强氧化应激和 H2O2 供给材料的内在抗肿瘤能力三个方面探讨了 H2O2 供给材料治疗肿瘤的机制。此外,还讨论了 H2O2- 供给材料在肿瘤治疗中的应用。最后,介绍了 H2O2 供给材料的未来。本综述旨在为 H2O2- 供给材料在肿瘤治疗中的应用提供一个新的思路。
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引用次数: 0
Splittable systems in biomedical applications. 生物医学应用中的可分割系统。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-07-16 DOI: 10.1039/d4bm00709c
Sichen Yuan, Alexa Bremmer, Xicheng Yang, Jiayue Li, Quanyin Hu

Splittable systems have emerged as a powerful approach for the precise spatiotemporal control of biological processes. This concept relies on splitting a functional molecule into inactive fragments, which can be reassembled under specific conditions or stimuli to regain activity. Several binding pairs and orthogonal split fragments are introduced by fusing with other modalities to develop more complex and robust designs. One of the pillars of these splittable systems is modularity, which involves decoupling targeting, activation, and effector functions. Challenges, such as off-target effects and overactivation, can be addressed through precise control. This review provides an overview of the design principles, strategies, and applications of splittable systems across diverse fields including immunotherapy, gene editing, prodrug activation, biosensing, and synthetic biology.

可分裂系统已成为精确时空控制生物过程的有力方法。这一概念依赖于将功能分子拆分成非活性片段,然后在特定条件或刺激下重新组装以恢复活性。通过与其他模式的融合,引入了多个结合对和正交分裂片段,从而开发出更复杂、更强大的设计。这些可拆分系统的支柱之一是模块化,其中包括解耦靶向、激活和效应器功能。脱靶效应和过度激活等挑战可以通过精确控制来解决。本综述概述了可拆分系统的设计原理、策略和在免疫疗法、基因编辑、原药激活、生物传感和合成生物学等不同领域的应用。
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引用次数: 0
Design Considerations and Biomaterials Selection in Embedded Extrusion 3D Bioprinting 嵌入式挤压三维生物打印中的设计考虑因素和生物材料选择
IF 6.6 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-07-15 DOI: 10.1039/d4bm00550c
Swaprakash Yogeshwaran, Hossein Goodarzi Hosseinabadi, Daniel Ehab Gendy, Amir K. Miri
In embedded extrusion 3D bioprinting, a temporary matrix preserves a paste-like filament ejecting from a narrow nozzle. For granular sacrificial matrices, the methodology is known as the freeform reversible embedding of suspended hydrogels (FRESH). Embedded extrusion 3D bioprinting methods result in more rapid and controlled manufacturing of cell-laden tissue constructs, particularly vascular and multi-component structures. This report focuses on the working principles and bioink design criteria for implementing conventional embedded extrusion and FRESH 3D bioprinting strategies. We also present a set of experimental data as a guideline for selecting the support bath or matrix. We discuss the advantages of embedded extrusion methods over conventional biomanufacturing methods. This work will provide a short recipe for selecting inks and printing parameters for desired shapes in embedded extrusion and FRESH 3D bioprinting methods.
在嵌入式挤压三维生物打印技术中,临时基质可保存从狭窄喷嘴喷出的糊状长丝。对于颗粒状牺牲基质,这种方法被称为悬浮水凝胶的自由形态可逆嵌入(FRESH)。嵌入式挤压三维生物打印方法能更快速、更可控地制造出含有细胞的组织结构,尤其是血管和多组分结构。本报告重点介绍了实施传统嵌入挤压和 FRESH 三维生物打印策略的工作原理和生物墨水设计标准。我们还提供了一组实验数据,作为选择支撑浴或基质的指导。我们讨论了嵌入式挤压方法相对于传统生物制造方法的优势。这项工作将为嵌入式挤压和 FRESH 三维生物打印方法中理想形状的油墨和打印参数的选择提供简易配方。
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引用次数: 0
The semi-interpenetrating network hydrogel loaded with Oridonin and DNase-I on healing of chemoradiotherapy-induced oral mucositis 负载奥利多宁和 DNase-I 的半穿透性网络水凝胶对化疗引起的口腔黏膜炎愈合的影响
IF 6.6 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-07-11 DOI: 10.1039/d4bm00114a
Yuxue Pan, Mengyuan Wang, Peng Wang, Hongliang Wei, Xiangjuan Wei, Dongmei Wang, Yongwei Hao, Yongxue Wang, Hongli Chen
Oral mucositis (OM) is a common side effect experienced by cancer patients undergoing chemotherapy and/or radiotherapy. In this study, we developed a semi-interpenetrating network hydrogel (IPN) that is suitable for adhesion to oral mucous membranes and gradual degradation in the oral environment. This IPN was based on the combination of ε-polylysine (PLL) and Hetastarch (HES), loaded with DNase-I and Oridonin (ORI) (ORI/DNase-I/IPN) for the treatment of OM. In vitro studies were conducted to evaluate degradation, adhesion, release analysis, as well as bioactivity including cell proliferation and wound healing assays using epidermal keratinocyte and fibroblast cell lines. Furthermore, the therapeutic effects of ORI/DNase-I/IPN were investigated in vivo using Sprague-Dawley (SD) rats with chemoradiotherapy-induced OM. The results demonstrated that the IPN exhibited excellent adhesion to wet mucous membranes, and the two drugs co-encapsulated in the hydrogel were released in a controlled manner. The in vivo wound repair effect, microbiological assays, H&E and Masson staining supported the non-toxicity of ORI/DNase-I/IPN, as well as its ability to accelerate the healing of oral ulcers and reduce inflammation. Overall, ORI/DNase-I/IPN demonstrated a therapeutic effect on oral ulcers in rats by significantly accelerating the healing process and reducing inflammation. These findings provide new insights into possible therapies for OM.
口腔黏膜炎(OM)是接受化疗和/或放疗的癌症患者常见的副作用。在这项研究中,我们开发了一种适合粘附在口腔粘膜上并在口腔环境中逐渐降解的半穿透性网络水凝胶(IPN)。这种 IPN 基于ε-聚赖氨酸(PLL)和 Hetastarch(HES)的组合,负载有 DNase-I 和 Oridonin(ORI)(ORI/DNase-I/IPN),用于治疗 OM。体外研究评估了降解、粘附、释放分析以及生物活性,包括使用表皮角质细胞和成纤维细胞系进行的细胞增殖和伤口愈合试验。此外,研究人员还利用化放疗诱发的Sprague-Dawley(SD)大鼠对ORI/DNase-I/IPN的治疗效果进行了体内研究。结果表明,IPN 对湿黏膜具有良好的粘附性,水凝胶中的两种药物以可控方式释放。体内伤口修复效果、微生物检测、H&E 和 Masson 染色均证明 ORI/DNase-I/IPN 无毒性,并能加速口腔溃疡愈合和减轻炎症反应。总之,ORI/DNase-I/IPN 对大鼠口腔溃疡有治疗作用,能显著加快愈合过程并减轻炎症反应。这些发现为口腔溃疡的可能疗法提供了新的视角。
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引用次数: 0
Ultrasmall Magnolol/Ebselen Nanomicelles for Preventing Renal Ischemia/Reperfusion Injury 用于预防肾缺血/再灌注损伤的超小型木兰醇/易倍申纳米细胞
IF 6.6 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-07-11 DOI: 10.1039/d4bm00614c
Chang Liu, Linhua Li, Li Li, Qingyin Li, Jing Liu, Chunle Zhang, Zhengjiang Cao, Liang Ma, Xiaoxi Zeng, Ping Fu
Renal ischemia/reperfusion injury (RIRI) is an inevitable complication following kidney transplantation surgery, accompanied by the generation of massive of free radicals. The cascade of events including oxidative stress, extreme inflammation, cellular apoptosis, thrombosis disrupts the microenvironment of renal cells and the hematological system, ultimately leading to the development of acute kidney injury/ failure. Current research primarily focuses on reducing inflammation and mitigating damage to renal cells through antioxidative approaches. However, studies on simultaneously modulating the renal hematologic system remain unreported. Herein, a potent and novel drug-loaded nanomicelles can be efficiently self-assembled with magnolol (MG) and ebselen (EBS) by the π-π conjugation, hydrophobic action and the surfactant properties of Tween-80. The ultrasmall MG/EBS nanomicelles (Average particle size: 10–25 nm) not only fully preserve the activity of both drugs but also greatly enhance drug utilization (encapsulation rates: MG-90.1%, EBS-49.3%) and reduce drug toxicity. Furthermore, EBS, as a glutathione peroxidase mimic and NO catalyst, synergistically collaborates with the multifunctional MG to scavenge free radicals, significantly inhibiting inflammation and thrombosis while effectively preventing apoptosis of vascular endothelial cells and renal tubular epithelial cells. This study provides a new strategy and theoretical foundation for the simultaneous regulation of kidney cells and blood microenvironment stability.
肾缺血再灌注损伤(RIRI)是肾移植手术后不可避免的并发症,伴随着大量自由基的产生。氧化应激、极度炎症、细胞凋亡、血栓形成等一系列事件破坏了肾脏细胞和血液系统的微环境,最终导致急性肾损伤/肾衰竭的发生。目前的研究主要集中在通过抗氧化方法减轻炎症和减轻对肾细胞的损伤。然而,关于同时调节肾脏血液系统的研究仍未见报道。在本文中,通过π-π共轭、疏水作用和吐温-80的表面活性剂特性,一种强效的新型药物负载纳米细胞可与木酚(MG)和依布仑(EBS)有效地自组装。超小 MG/EBS 纳米微孔(平均粒径:10-25 nm)不仅能充分保留两种药物的活性,还能大大提高药物利用率(包封率:MG-90.1%,EBS-49.3%)并降低药物毒性。此外,EBS 作为谷胱甘肽过氧化物酶模拟物和氮氧化物催化剂,与多功能 MG 协同清除自由基,显著抑制炎症和血栓形成,同时有效防止血管内皮细胞和肾小管上皮细胞凋亡。这项研究为同时调控肾脏细胞和血液微环境的稳定性提供了新的策略和理论基础。
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引用次数: 0
A novel bi-layered asymmetric membrane incorporating demineralized dentin matrix accelerates tissue healing and bone regeneration in a rat skull defect model. 在大鼠颅骨缺损模型中,含有脱矿质牙本质基质的新型双层不对称膜可加速组织愈合和骨再生。
IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2024-07-10 DOI: 10.1039/d4bm00350k
Yan-Fei Li, Qi-Pei Luo, Yu-Xin Yang, An-Qi Li, Xin-Chun Zhang

Objectives: The technique of guided bone regeneration (GBR) has been widely used in the field of reconstructive dentistry to address hard tissue deficiency. The objective of this research was to manufacture a novel bi-layered asymmetric membrane that incorporates demineralized dentin matrix (DDM), a bioactive bone replacement derived from dentin, in order to achieve both soft tissue isolation and hard tissue regeneration simultaneously. Methods: DDM particles were harvested from healthy, caries-free permanent teeth. The electrospinning technique was utilized to synthesize bi-layered DDM-loaded PLGA/PLA (DPP) membranes. We analyzed the DPP bilayer membranes' surface topography, physicochemical properties and degradation ability. Rat skull critical size defects (CSDs) were constructed to investigate in vivo bone regeneration. Results: The synthesized DPP bilayer membranes possessed suitable surface characteristics, acceptable mechanical properties, good hydrophilicity, favorable apatite forming ability and suitable degradability. Micro-computed tomography (CT) showed significantly more new bone formation in the rat skull defects implanted with the DPP bilayer membranes. Histological evaluation further revealed that the bone was more mature with denser bone trabeculae. In addition, the DPP bilayer membrane significantly promoted the expression of the OCN matrix protein in vivo. Conclusions: The DPP bilayer membranes exhibited remarkable biological safety and osteogenic activity in vivo and showed potential as a prospective candidate for GBR applications in the future.

目的:引导骨再生(GBR)技术已广泛应用于牙科整形领域,以解决硬组织缺损问题。本研究的目的是制造一种新型双层非对称膜,该膜含有脱矿化牙本质基质(DDM),这是一种从牙本质中提取的生物活性骨替代物,可同时实现软组织隔离和硬组织再生。方法从健康无龋恒牙中提取 DDM 颗粒。利用电纺丝技术合成双层 DDM 加载 PLGA/PLA (DPP)膜。我们分析了 DPP 双层膜的表面形貌、理化性质和降解能力。通过构建大鼠颅骨临界尺寸缺损(CSD)来研究体内骨再生。结果合成的 DPP 双层膜具有合适的表面特征、可接受的机械性能、良好的亲水性、有利的磷灰石形成能力和合适的降解性。显微计算机断层扫描(CT)显示,植入 DPP 双层膜的大鼠颅骨缺损处新骨形成明显增多。组织学评估进一步显示,骨骼更加成熟,骨小梁更加密集。此外,DPP双层膜还能明显促进体内OCN基质蛋白的表达。结论DPP 双层膜在体内表现出显著的生物安全性和成骨活性,有望成为未来 GBR 应用的候选材料。
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Biomaterials Science
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