Alginates

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  • 文章类型: Journal Article
    煤炭行业的逐渐衰落需要开发有效的酸性矿井排水处理解决方案(AMD),其特征是高酸度和高浓度的重金属。这项研究提出了一种创新的方法,利用硫酸盐还原细菌(SRB)适应污染的厌氧环境。本研究的重点是阐明SRB的生理特性和最佳生长条件。特别是与pH值和温度有关。实验结果表明,在30°C的最佳温度下,SRB的硫酸盐去除率为88.86%。此外,使用海藻酸钠(SA)和羧甲基纤维素(CMC)配制SRB凝胶颗粒,并在特定条件下(pH=6,C/S=1.5,T=30°C,CMC=4.5%,BSNa=0.4mol/L,和交联时间=9小时)。在这些条件下,SRB凝胶颗粒表现出91.6%的增强的硫酸盐去除效率。通过差示扫描量热法(DSC)和热重分析(TGA)的热分析提供了对SRB凝胶球的稳定性和性质的进一步了解。这些发现强调了基于SRB的生物修复作为一种可持续和有效的AMD治疗方法的潜力。提供一种新颖的环保解决方案,以减轻环境污染的不利影响。
    The progressive decline of the coal industry necessitates the development of effective treatment solutions for acid mine drainage (AMD), which is characterized by high acidity and elevated concentrations of heavy metals. This study proposes an innovative approach leveraging sulfate-reducing bacteria (SRB) acclimated to contaminated anaerobic environments. The research focused on elucidating the physiological characteristics and optimal growth conditions of SRB, particularly in relation to the pH level and temperature. The experimental findings reveal that the SRB exhibited a sulfate removal rate of 88.86% at an optimal temperature of 30 °C. Additionally, SRB gel particles were formulated using sodium alginate (SA) and carboxymethyl cellulose (CMC), and their performance was assessed under specific conditions (pH = 6, C/S = 1.5, T = 30 °C, CMC = 4.5%, BSNa = 0.4 mol/L, and cross-linking time = 9 h). Under these conditions, the SRB gel particles demonstrated an enhanced sulfate removal efficiency of 91.6%. Thermal analysis via differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) provided further insights into the stability and properties of the SRB gel spheres. The findings underscore the potential of SRB-based bioremediation as a sustainable and efficient method for AMD treatment, offering a novel and environmentally friendly solution to mitigating the adverse effects of environmental contamination.
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  • 文章类型: Journal Article
    在我们寻找生物相容性复合止血敷料的过程中,我们专注于由两种天然生物成分组成的新型生物材料的设计,胶原蛋白和海藻酸钠(SA),使用1-乙基-3-(3-二甲基氨基丙基)碳二亚胺/N-羟基琥珀酰亚胺(EDC/NHS)和氧化藻酸钠(OSA)交联。我们进行了一系列测试,以评估其理化性质,急性全身毒性,皮肤刺激,皮内反应,致敏,细胞毒性,和体内股动脉出血模型。结果证明了胶原/海藻酸钠(C/SA)基敷料在交联前后具有优异的生物相容性。具体来说,股动脉出血模型显示,EDC/NHS交联敷料与空白组纱布相比,止血时间显著缩短,为132.5±12.82s(止血时间为251.43±10.69s).这些发现表明,基于C/SA的敷料具有良好的生物相容性和显着的止血效果。使它们适合生物医学应用。
    In our search for a biocompatible composite hemostatic dressing, we focused on the design of a novel biomaterial composed of two natural biological components, collagen and sodium alginate (SA), cross-linked using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) and oxidized sodium alginate (OSA). We conducted a series of tests to evaluate the physicochemical properties, acute systemic toxicity, skin irritation, intradermal reaction, sensitization, cytotoxicity, and in vivo femoral artery hemorrhage model. The results demonstrated the excellent biocompatibility of the collagen/sodium alginate (C/SA)-based dressings before and after crosslinking. Specifically, the femoral artery hemorrhage model revealed a significantly shortened hemostasis time of 132.5 ± 12.82 s for the EDC/NHS cross-linked dressings compared to the gauze in the blank group (hemostasis time of 251.43 ± 10.69 s). These findings indicated that C/SA-based dressings exhibited both good biocompatibility and a significant hemostatic effect, making them suitable for biomedical applications.
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  • 文章类型: Journal Article
    节段性骨缺损,由于创伤等因素,肿瘤切除,先天性畸形,提出了重大的临床挑战,通常需要复杂的重建策略。负载有多种骨生成促进成分的水凝胶已成为修复骨缺损的有希望的工具。虽然先前已经证明了Piezo1激动剂Yoda1的成骨潜力,其疏水性质对有效加载到水凝胶基质上提出了挑战。在这项研究中,我们通过使用Yoda1预处理的骨髓间充质干细胞(BMSCs)外泌体(Exo-Yoda1)和BMSCs(Exo-MSC)外泌体来应对这一挑战.相对而言,与对照组和Exo-MSC处理的对应物相比,Exo-Yoda1处理的BMSC表现出增强的成骨能力。值得注意的是,Exo-Yoda1处理的细胞表现出与Yoda1本身相似的功能。转录组分析显示成骨相关信号通路的激活,表明Yoda1介导的信号如ErK的潜在转导,这项研究验证了这一发现。此外,我们成功地将Exo-Yoda1整合到明胶甲基丙烯酰(GelMA)/甲基丙烯酸海藻酸钠(SAMA)/β-磷酸三钙(β-TCP)水凝胶中。这些加载Exo-Yoda1的水凝胶在皮下异位成骨裸鼠模型和大鼠颅骨骨缺损模型中显示出增强的成骨作用。总之,我们的研究引入了Exo-Yoda1负载的GELMA/SAMA/β-TCP水凝胶作为促进成骨的有希望的方法。这种创新策略对于骨缺损重建领域的未来广泛临床应用具有重要意义。
    Segmental bone defects, arising from factors such as trauma, tumor resection, and congenital malformations, present significant clinical challenges that often necessitate complex reconstruction strategies. Hydrogels loaded with multiple osteogenesis-promoting components have emerged as promising tools for bone defect repair. While the osteogenic potential of the Piezo1 agonist Yoda1 has been demonstrated previously, its hydrophobic nature poses challenges for effective loading onto hydrogel matrices.In this study, we address this challenge by employing Yoda1-pretreated bone marrow-derived mesenchymal stem cell (BMSCs) exosomes (Exo-Yoda1) alongside exosomes derived from BMSCs (Exo-MSC). Comparatively, Exo-Yoda1-treated BMSCs exhibited enhanced osteogenic capabilities compared to both control groups and Exo-MSC-treated counterparts. Notably, Exo-Yoda1-treated cells demonstrated similar functionality to Yoda1 itself. Transcriptome analysis revealed activation of osteogenesis-associated signaling pathways, indicating the potential transduction of Yoda1-mediated signals such as ErK, a finding validated in this study. Furthermore, we successfully integrated Exo-Yoda1 into gelatin methacryloyl (GelMA)/methacrylated sodium alginate (SAMA)/β-tricalcium phosphate (β-TCP) hydrogels. These Exo-Yoda1-loaded hydrogels demonstrated augmented osteogenesis in subcutaneous ectopic osteogenesis nude mice models and in rat skull bone defect model. In conclusion, our study introduces Exo-Yoda1-loaded GELMA/SAMA/β-TCP hydrogels as a promising approach to promoting osteogenesis. This innovative strategy holds significant promise for future widespread clinical applications in the realm of bone defect reconstruction.
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  • 文章类型: Journal Article
    水凝胶被广泛用作组织支架的生物材料,它们的受控制造一直是广泛调查的主题。然而,通过配方控制繁琐的机械性能调节过程阻碍了它们在多种组织支架中的应用。为了克服这个限制,我们提出了一个两步过程来实现机械模量在宽范围内的简单调整,通过组合数字光处理(DLP)和后处理步骤。紫外线固化水凝胶(聚丙烯酰胺-藻酸盐)通过DLP3D打印,具有创建复杂3D图案的能力。随后用Fe3离子浴进行后处理会引起水凝胶支架的二次交联,通过浸泡在具有不同Fe3+浓度的溶液中根据需要调整模量。这种创新的两步工艺提供了高精度(10μm)和宽模量调节能力(15.8-345kPa),覆盖人体广泛的组织。作为一个实际的示范,打印具有组织模拟模式的水凝胶支架,用于培养心脏组织和血管支架,能有效支持组织生长并诱导组织形态。
    Hydrogels are extensively explored as biomaterials for tissue scaffolds, and their controlled fabrication has been the subject of wide investigation. However, the tedious mechanical property adjusting process through formula control hindered their application for diverse tissue scaffolds. To overcome this limitation, we proposed a two-step process to realize simple adjustment of mechanical modulus over a broad range, by combining digital light processing (DLP) and post-processing steps. UV-curable hydrogels (polyacrylamide-alginate) are 3D printed via DLP, with the ability to create complex 3D patterns. Subsequent post-processing with Fe3+ ions bath induces secondary crosslinking of hydrogel scaffolds, tuning the modulus as required through soaking in solutions with different Fe3+ concentrations. This innovative two-step process offers high-precision (10 μm) and broad modulus adjusting capability (15.8-345 kPa), covering a broad range of tissues in the human body. As a practical demonstration, hydrogel scaffolds with tissue-mimicking patterns were printed for cultivating cardiac tissue and vascular scaffolds, which can effectively support tissue growth and induce tissue morphologies.
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  • 文章类型: Journal Article
    重要牙髓疗法(VPT)被认为是一种保守治疗方法,可在龋齿和外伤引起的牙髓炎中保持牙髓活力。然而,矿物三氧化物骨料(MTA)作为最常用的修补材料,在炎症条件下表现出有限的功效。这项研究介绍了一种创新的纳米复合水凝胶,同时针对抗炎和牙本质矿化,旨在有效地保存重要的牙髓组织。
    通过将L-精氨酸修饰的磷酸钙/磷酸锌纳米颗粒(L-(CaP-ZnP)NP)与海藻酸钠(SA)相结合,设计了L-(CaP-ZnP)/SA纳米复合水凝胶,并用TEM表征,SEM,FTIR,EDX,ICP-AES,和Zeta潜力。体外,我们评估了细胞毒性和抗炎特性。人牙髓干细胞(hDPSC)与脂多糖(LPS)一起培养以诱导炎症反应,并通过碱性磷酸酶(ALP)/茜素红S(ARS)染色检测细胞牙源性分化,探索可能的信号通路,qRT-PCR,免疫荧光染色,和西方印迹,分别。在体内,通过苏木精和伊红(HE)染色和免疫组织化学染色,利用牙髓炎模型探索L-(CaP-ZnP)/SA纳米复合水凝胶在控制牙髓炎症和增强牙本质矿化中的潜力.
    体外实验表明,成功合成了纳米复合水凝胶,并表现出理想的生物相容性。在炎症条件下,与MTA相比,L-(CaP-ZnP)/SA纳米复合水凝胶表现出优异的抗炎和促牙本质形成作用。此外,纳米复合水凝胶显着增强p38磷酸化,p38信号通路参与牙髓修复。重要的是,在大鼠牙髓炎模型中,L-(CaP-ZnP)/SA纳米复合水凝胶下调炎症标志物,同时上调矿化相关标志物,从而刺激形成强大的修复性牙本质。
    具有良好生物相容性的L-(CaP-ZnP)/SA纳米复合水凝胶通过激活p38信号通路有效促进炎症消退和增强牙本质矿化,作为纸浆封盖材料,为牙髓炎的治疗提供了一个有前途的和先进的解决方案。
    UNASSIGNED: Vital pulp therapy (VPT) is considered a conservative treatment for preserving pulp viability in caries and trauma-induced pulpitis. However, Mineral trioxide aggregate (MTA) as the most frequently used repair material, exhibits limited efficacy under inflammatory conditions. This study introduces an innovative nanocomposite hydrogel, tailored to simultaneously target anti-inflammation and dentin mineralization, aiming to efficiently preserve vital pulp tissue.
    UNASSIGNED: The L-(CaP-ZnP)/SA nanocomposite hydrogel was designed by combining L-Arginine modified calcium phosphate/zinc phosphate nanoparticles (L-(CaP-ZnP) NPs) with sodium alginate (SA), and was characterized with TEM, SEM, FTIR, EDX, ICP-AES, and Zeta potential. In vitro, we evaluated the cytotoxicity and anti-inflammatory properties. Human dental pulp stem cells (hDPSCs) were cultured with lipopolysaccharide (LPS) to induce an inflammatory response, and the cell odontogenic differentiation was measured and possible signaling pathways were explored by alkaline phosphatase (ALP)/alizarin red S (ARS) staining, qRT-PCR, immunofluorescence staining, and Western blotting, respectively. In vivo, a pulpitis model was utilized to explore the potential of the L-(CaP-ZnP)/SA nanocomposite hydrogel in controlling pulp inflammation and enhancing dentin mineralization by Hematoxylin and eosin (HE) staining and immunohistochemistry staining.
    UNASSIGNED: In vitro experiments revealed that the nanocomposite hydrogel was synthesized successfully and presented desirable biocompatibility. Under inflammatory conditions, compared to MTA, the L-(CaP-ZnP)/SA nanocomposite hydrogel demonstrated superior anti-inflammatory and pro-odontogenesis effects. Furthermore, the nanocomposite hydrogel significantly augmented p38 phosphorylation, implicating the involvement of the p38 signaling pathway in pulp repair. Significantly, in a rat pulpitis model, the L-(CaP-ZnP)/SA nanocomposite hydrogel downregulated inflammatory markers while upregulating mineralization-related markers, thereby stimulating the formation of robust reparative dentin.
    UNASSIGNED: The L-(CaP-ZnP)/SA nanocomposite hydrogel with good biocompatibility efficiently promoted inflammation resolution and enhanced dentin mineralization by activating p38 signal pathway, as a pulp-capping material, offering a promising and advanced solution for treatment of pulpitis.
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  • 文章类型: Journal Article
    骨组织工程(BTE)是一种有前途的替代自体骨移植的临床治疗骨缺损,无机/有机复合水凝胶作为BTE支架是当前研究的热点。纳米羟基磷灰石/明胶甲基丙烯酸酯/氧化海藻酸钠(nHAP/GelMA/OSA)的构建,缩写为HGO,复合水凝胶加载骨形态发生蛋白7(BMP7)将提供一个合适的三维微环境,以促进细胞聚集,扩散,和差异化,从而促进骨修复和再生。
    通过将GelMA和OSA组合制备了双重交联的水凝胶,而HGO水凝胶通过掺入不同量的nHAP来配制。对水凝胶进行物理和化学表征,然后评估其生物相容性。BMP7-HGO(BHGO)水凝胶通过将合适浓度的BMP7掺入到HGO水凝胶中来制备。然后通过体外实验并使用大鼠股骨缺损模型验证BHGO水凝胶的成骨潜力。
    nHAP的添加显着改善了水凝胶的物理性质,和10%nHAP的复合水凝胶在所有组中表现出最佳的整体性能。选定浓度的HGO水凝胶用作BMP7负载的载体,并在体内和体外评估其成骨潜力。与空白对照中观察到的结果相比,BHGO水凝胶显示出优异的体外成骨诱导和体内修复骨组织的潜力。BMP7和HGO组。
    使用含有10%HGO的水凝胶似乎有望用于骨组织工程支架,特别是当负载BMP7以增强其成骨潜力时。然而,需要进一步的调查来优化GelMA,OSA,和nHAP比率,随着BMP7的浓度,最大限度地发挥成骨潜力。
    UNASSIGNED: Bone tissue engineering (BTE) is a promising alternative to autologous bone grafting for the clinical treatment of bone defects, and inorganic/organic composite hydrogels as BTE scaffolds are a hot spot in current research. The construction of nano-hydroxyapatite/gelatin methacrylate/oxidized sodium alginate (nHAP/GelMA/OSA), abbreviated as HGO, composite hydrogels loaded with bone morphogenetic protein 7 (BMP7) will provide a suitable 3D microenvironment to promote cell aggregation, proliferation, and differentiation, thus facilitating bone repair and regeneration.
    UNASSIGNED: Dually-crosslinked hydrogels were fabricated by combining GelMA and OSA, while HGO hydrogels were formulated by incorporating varying amounts of nHAP. The hydrogels were physically and chemically characterized followed by the assessment of their biocompatibility. BMP7-HGO (BHGO) hydrogels were fabricated by incorporating suitable concentrations of BMP7 into HGO hydrogels. The osteogenic potential of BHGO hydrogels was then validated through in vitro experiments and using rat femoral defect models.
    UNASSIGNED: The addition of nHAP significantly improved the physical properties of the hydrogel, and the composite hydrogel with 10% nHAP demonstrated the best overall performance among all groups. The selected concentration of HGO hydrogel served as a carrier for BMP7 loading and was evaluated for its osteogenic potential both in vivo and in vitro. The BHGO hydrogel demonstrated superior in vitro osteogenic induction and in vivo potential for repairing bone tissue compared to the outcomes observed in the blank control, BMP7, and HGO groups.
    UNASSIGNED: Using hydrogel containing 10% HGO appears promising for bone tissue engineering scaffolds, especially when loaded with BMP7 to boost its osteogenic potential. However, further investigation is needed to optimize the GelMA, OSA, and nHAP ratios, along with the BMP7 concentration, to maximize the osteogenic potential.
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  • 文章类型: Journal Article
    溃疡性结肠炎(UC)的口服药物通常受到诸如积累不足等挑战的阻碍,粘液屏障的有限渗透,以及减轻过度ROS和炎性细胞因子的复杂任务。这里,我们提出了一种针对UC的靶向治疗的策略,该策略涉及海藻酸钠微球(SAMs),其中包含M2巨噬细胞膜(M2M)包被的Janus纳米马达(命名为Motor@M2M).SAM提供保护屏障,确保Motor@M2M能够承受恶劣的胃环境,并表现出受控的释放。M2M增强纳米马达对炎性组织的靶向精度并且充当炎性细胞因子的中和的诱饵。MnO2在氧化微环境中催化分解H2O2会产生O2气泡,推动马达@M2M穿过粘液屏障进入发炎的结肠组织。口服后,运动@M2M@SAM显著改善UC严重程度,包括炎症缓解,ROS清除,巨噬细胞重编程,以及肠道屏障和微生物群的恢复。因此,我们的研究介绍了一种有前途的口服微球配方的巨噬细胞-仿生纳米机器人,为UC治疗提供了一种有希望的方法。
    Oral medication for ulcerative colitis (UC) is often hindered by challenges such as inadequate accumulation, limited penetration of mucus barriers, and the intricate task of mitigating excessive ROS and inflammatory cytokines. Here, we present a strategy involving sodium alginate microspheres (SAMs) incorporating M2 macrophage membrane (M2M)-coated Janus nanomotors (denominated as Motor@M2M) for targeted treatment of UC. SAM provides a protective barrier, ensuring that Motor@M2M withstands the harsh gastric milieu and exhibits controlled release. M2M enhances the targeting precision of nanomotors to inflammatory tissues and acts as a decoy for the neutralization of inflammatory cytokines. Catalytic decomposition of H2O2 by MnO2 in the oxidative microenvironment generates O2 bubbles, propelling Motor@M2M across the mucus barrier into inflamed colon tissues. Upon oral administration, Motor@M2M@SAM notably ameliorated UC severity, including inflammation mitigation, ROS scavenging, macrophage reprogramming, and restoration of the intestinal barrier and microbiota. Consequently, our investigation introduces a promising oral microsphere formulation of macrophage-biomimetic nanorobots, providing a promising approach for UC treatment.
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  • 文章类型: Journal Article
    重金属(HMs)造成的污染由于其严重的环境威胁而引起全球关注。光合蓝细菌具有天然生态位和修复镉等HMs的能力。然而,它们的实际应用受到对HMs的低耐受性和与回收相关的问题的阻碍。为了应对这些挑战,这项研究的重点是开发和评估用于HMs生物修复的工程蓝藻生物材料。将编码植物螯合素(PCSs)和金属硫蛋白(MTs)的基因引入了蓝细菌Synechocystissp。PCC6803,创建PM/6803。该菌株对多种HMs表现出改进的耐受性,并有效去除Cd2+的组合,Zn2+,和Cu2+。以Cd2+为代表,PM/6803在给定的测试条件下实现了大约21μgCd2+/OD750的生物修复率。为了便于其可控应用,PM/6803使用基于藻酸钠的水凝胶(PM/6803@SA)进行封装,以创建具有不同形状的“生命材料”。这个系统是可行的,生物相容性在模拟斑马鱼和小鼠模型条件下对Cd2+的去除效果良好。简而言之,体外应用PM/6803@SA从含有Cd2+的污染水中有效拯救斑马鱼,而体内使用PM/6803@SA可显着降低小鼠体内Cd2含量并恢复其活动行为。该研究提供了在体外和体内使用工程蓝细菌的有趣生物材料进行HMs生物修复的可行策略。
    The pollution caused by heavy metals (HMs) represents a global concern due to their serious environmental threat. Photosynthetic cyanobacteria have a natural niche and the ability to remediate HMs such as cadmium. However, their practical application is hindered by a low tolerance to HMs and issues related to recycling. In response to these challenges, this study focuses on the development and evaluation of engineered cyanobacteria-based living materials for HMs bioremediation. Genes encoding phytochelatins (PCSs) and metallothioneins (MTs) were introduced into the model cyanobacterium Synechocystis sp. PCC 6803, creating PM/6803. The strain exhibited improved tolerance to multiple HMs and effectively removed a combination of Cd2+, Zn2+, and Cu2+. Using Cd2+ as a representative, PM/6803 achieved a bioremediation rate of approximately 21 μg of Cd2+/OD750 under the given test conditions. To facilitate its controllable application, PM/6803 was encapsulated using sodium alginate-based hydrogels (PM/6803@SA) to create \"living materials\" with different shapes. This system was feasible, biocompatible, and effective for removing Cd2+ under simulated conditions of zebrafish and mice models. Briefly, in vitro application of PM/6803@SA efficiently rescued zebrafish from polluted water containing Cd2+, while in vivo use of PM/6803@SA significantly decreased the Cd2+ content in mice bodies and restored their active behavior. The study offers feasible strategies for HMs bioremediation using the interesting biomaterials of engineered cyanobacteria both in vitro and in vivo.
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  • 文章类型: Journal Article
    感音神经性听力损失(SNHL)主要由内耳毛细胞(HCs)和相关螺旋神经节神经元(SGN)的损伤或损失引起。目前,SNHL在临床上仍然没有有效的治疗方法。最近,类器官的发展为SNHL的研究和治疗带来了广阔的前景。同时,三维(3D)打印为构建用于组织工程和再生医学的多功能类器官提供了巨大的机会。在这项研究中,明胶(凝胶),海藻酸钠(SA),采用聚乙烯醇(PVA)和3D打印技术制备仿生支架。将新生小鼠内耳来源的Corti器官接种在PVA/Gel/SA支架上,构建Corti类器官。然后,用Corti类器官研究硫酸小檗碱对新霉素听觉HC和SGN的潜在保护作用。结果表明,PVA/Gel/SA仿生三维支架具有良好的细胞相容性和力学性能。构建的类器官可以在体外很好地维持器官的Corti活性。此外,损伤干预结果显示硫酸小檗碱可显著抑制新霉素诱导的HC和SGN损伤。这项研究表明,制造的类器官对Corti的器官具有高度的仿生作用,这可能为药物开发提供有效的模式,SNHL的细胞和基因治疗。
    Sensorineural hearing loss (SNHL) is mainly caused by injury or loss of hair cells (HCs) and associated spiral ganglion neurons (SGNs) in the inner ear. At present, there is still no effective treatment for SNHL in clinic. Recently, advances in organoid bring a promising prospect for research and treatment of SNHL. Meanwhile, three-dimensional (3D) printing provides a tremendous opportunity to construct versatile organoids for tissue engineering and regenerative medicine. In this study, gelatin (Gel), sodium alginate (SA), and polyvinyl alcohol (PVA) were used to fabricate biomimetic scaffold through 3D printing. The organ of Corti derived from neonatal mice inner ear was seeded on the PVA/Gel/SA scaffold to construct organ of Corti organoid. Then, the organ of Corti organoid was used to study the potential protective effects of berberine sulfate on neomycin-juried auditory HCs and SGNs. The results showed that the PVA/Gel/SA biomimetic 3D scaffolds had good cytocompatibilities and mechanical properties. The constructed organoid could maintain organ of Corti activity well in vitro. In addition, the injury intervention results showed that berberine sulfate could significantly inhibit neomycin-induced HC and SGN damage. This study suggests that the fabricated organoid is highly biomimetic to the organ of Corti, which may provide an effective model for drug development, cell and gene therapy for SNHL.
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  • 文章类型: Journal Article
    人体肠道结构和功能在体外的准确复制对了解肠道的发育和疾病发生具有重要意义。然而,大多数体外研究通常局限于2D模型,2.5D器官芯片或3D类器官,不能完全概括组织结构,体内发现的微环境和细胞区室化。在这里,包含肠道特征的厘米级肠道组织,如中空管状结构,毛细血管和紧密相连的上皮,具有体内环状褶皱,地穴-绒毛,微绒毛是通过3D嵌入生物打印构建的。在我们的战略中,一种由甲基丙烯酸酯化明胶组成的新型光固化生物墨水,甲基丙烯酸酯化海藻酸钠和聚(乙二醇)二丙烯酸酯被开发用于制造肠道模型。通过模型的拓扑结构诱导植入腔内的Caco-2细胞产生微绒毛,地穴-绒毛,和紧密连接,模拟肠上皮屏障。模型内包裹的人脐静脉内皮细胞逐渐形成微血管,模仿肠道中密集的毛细血管网络。这个肠样组织,它非常类似于人类肠道的结构和细胞排列,可以作为预测新药对肠道的治疗和毒副作用的平台。
    Accurate reproduction of human intestinal structure and functionin vitrois of great significance for understanding the development and disease occurrence of the gut. However, mostin vitrostudies are often confined to 2D models, 2.5D organ chips or 3D organoids, which cannot fully recapitulate the tissue architecture, microenvironment and cell compartmentalization foundin vivo. Herein, a centimeter-scale intestine tissue that contains intestinal features, such as hollow tubular structure, capillaries and tightly connected epithelium with invivo-likering folds, crypt-villi, and microvilli is constructed by 3D embedding bioprinting. In our strategy, a novel photocurable bioink composed of methacrylated gelatin, methacrylated sodium alginate and poly (ethylene glycol) diacrylate is developed for the fabrication of intestinal model. The Caco-2 cells implanted in the lumen are induced by the topological structures of the model to derive microvilli, crypt-villi, and tight junctions, simulating the intestinal epithelial barrier. The human umbilical vein endothelial cells encapsulated within the model gradually form microvessels, mimicking the dense capillary network in the intestine. This intestine-like tissue, which closely resembles the structure and cell arrangement of the human gut, can act as a platform to predict the therapeutic and toxic side effects of new drugs on the intestine.
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