Bioactive Materials最新文献_第7页

In situ phosphorus-modified Mg2Ge/Zn-Cu composite with improved mechanical, degradation, biotribological properties, and in vitro and in vivo osteogenesis and osteointegration performance for biodegradable bone-implant applications 原位磷改性 Mg2Ge/Zn-Cu 复合材料具有更好的机械、降解和生物ribological 性能，以及体内外骨生成和骨整合性能，可用于生物降解骨植入应用

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-10-11 DOI: 10.1016/j.bioactmat.2024.09.026

Xian Tong , Xinkun Shen , Zhiqiang Lin , Runqi Zhou , Yue Han , Li Zhu , Shengbin Huang , Jianfeng Ma , Yuncang Li , Cuie Wen , Jixing Lin

Zinc (Zn)-based composites are promising biodegradable bone-implant materials because of their good biocompatibility, processability, and biodegradability. Nevertheless, the low interfacial bonding strength, coordinated deformation capacity, and mechanical strength of current Zn-based composites hinder their clinical application. In this study, we developed a biodegradable in situ 4Mg₂Ge/Zn-0.3Cu-0.05P composite (denoted ZMGCP) via phosphorus (P) modification and hot-rolling for bone-implant applications. The mechanical properties, corrosion behavior, biotribological performance, in vitro cytocompatibility and osteogenic differentiation, and in vivo osteogenesis and osteointegration of the as-cast (AC) and hot-rolled (HR) ZMGCP samples were systematically evaluated and compared to those of 4Mg₂Ge/Zn-0.3Cu (denoted ZMGC). The primary and eutectic reinforcement Mg₂Ge phases formed during solidification were refined after P modification and hot-rolling. The HR ZMGCP exhibited the best tensile properties among all the samples with an ultimate tensile strength of 288.9 MPa, a yield strength of 194.5 MPa, and an elongation of 17.7 %. The HR ZMGCP showed the lowest corrosion rate of 336 μm/a, 186 μm/a, and 61.7 μm/a as measured by potentiodynamic polarization, electrochemical impedance spectroscopy, and immersion testing, respectively, among all the samples in Hanks’ solution. The HR ZMGCP also showed higher biotribological resistance than its ZMGC counterpart. The HR ZMGCP exhibited the highest in vitro cytocompatibility, the best osteogenesis capability and angiogenesis property among the HR samples of pure Zn, ZMGC, and ZMGCP. Furthermore, the HR ZMGCP displayed complete in vivo biocompatibility, osteogenesis, osteointegration capability, and an appropriate degradation rate, showing significant potential for a biodegradable bone-implant material.

锌（Zn）基复合材料具有良好的生物相容性、可加工性和生物降解性，是一种很有前景的可生物降解骨植入材料。然而，目前锌基复合材料的界面结合强度、协调变形能力和机械强度较低，阻碍了其临床应用。在本研究中，我们通过磷（P）改性和热轧技术开发了一种可生物降解的原位 4Mg2Ge/Zn-0.3Cu-0.05P 复合材料（简称 ZMGCP），用于骨植入应用。系统地评估了铸造（AC）和热轧（HR）ZMGCP 样品的力学性能、腐蚀行为、生物ribological 性能、体外细胞相容性和成骨分化，以及体内成骨和骨整合，并与 4Mg2Ge/Zn-0.3Cu （ZMGC）进行了比较。经过 P 改性和热轧后，凝固过程中形成的初级和共晶强化 Mg2Ge 相得到了细化。在所有样品中，HR ZMGCP 的拉伸性能最好，极限拉伸强度为 288.9 兆帕，屈服强度为 194.5 兆帕，伸长率为 17.7%。在汉克斯溶液中，通过电位极化、电化学阻抗光谱和浸泡试验测量，HR ZMGCP 的腐蚀速率在所有样品中最低，分别为 336 μm/a、186 μm/a 和 61.7 μm/a。与 ZMGC 相比，HR ZMGCP 还表现出更高的生物抗性。在纯 Zn、ZMGC 和 ZMGCP 的 HR 样品中，HR ZMGCP 表现出最高的体外细胞相容性、最佳的成骨能力和血管生成特性。此外，HR ZMGCP 在体内表现出完全的生物相容性、成骨能力、骨整合能力和适当的降解率，显示出其作为可生物降解骨植入材料的巨大潜力。

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引用次数: 0

A natural polyphenolic nanoparticle--knotted hydrogel scavenger for osteoarthritis therapy 一种用于骨关节炎治疗的天然多酚纳米颗粒--打结水凝胶清除剂

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-10-11 DOI: 10.1016/j.bioactmat.2024.09.037

Qinfeng Ding , Yitong Wang , Tianyou Wang , Chengyao Zhang , Shengbing Yang , Lu Mao , Yiyun Cheng , Yiwen Li , Kaili Lin

Exploring highly efficient and cost-effective biomaterials for osteoarthritis (OA) treatment remains challenging, as current therapeutic strategies are difficult to eradicate the excessive reactive oxygen species (ROS) and nitric oxide (NO) at damaged sites. Tea polyphenol (TP) nanoparticles (NPs), a nature-inspired antioxidant in combination with 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), a NO scavenger, could provide maximized positive therapeutic effects on OA by eradicating both ROS and NO. Notably, this combination not only improves the half-life of the TP monomer and the drug loading efficiency of carboxy-PTIO but also prevents nitrite from being harmful to tissue. Moreover, the protonation ability of carboxy-PTIO allows smart acid-responsive release in response to environmental pH, which provides conditioned treatment strategies for OA. In in vitro experiments, TP/PTIO NPs downregulated proinflammatory cytokine release via synergistic removal of ROS and NO and suppression of ROS/NF-κB and iNOS/NO/Caspase-3 signaling. For in vivo experiments, NPs were cross-linked with 4-arm-PEG-SH to form an injectable hydrogel system. The release of TP and carboxy-PTIO from the system efficiently prevents cartilage inflammation and damage via similar signaling pathways. Overall, the proposed system provides an efficient approach for OA therapy.

由于目前的治疗策略难以消除受损部位过多的活性氧（ROS）和一氧化氮（NO），因此探索用于骨关节炎（OA）治疗的高效、经济的生物材料仍具有挑战性。茶多酚（TP）纳米颗粒（NPs）是一种源自大自然的抗氧化剂，与 2-(4-羧基苯基)-4,4,5,5-四甲基咪唑啉-1-氧-3-氧化物（羧基-PTIO）（一种一氧化氮清除剂）结合使用，可通过消除 ROS 和一氧化氮对 OA 产生最大的积极治疗效果。值得注意的是，这种组合不仅能提高 TP 单体的半衰期和羧基-PTIO 的药物负载效率，还能防止亚硝酸盐对组织造成危害。此外，羧基-PTIO 的质子化能力可根据环境酸碱度进行智能酸响应释放，从而为 OA 提供条件性治疗策略。在体外实验中，TP/PTIO NPs通过协同清除ROS和NO以及抑制ROS/NF-κB和iNOS/NO/Caspase-3信号传导，降低了促炎细胞因子的释放。在体内实验中，NPs 与 4-arm-PEG-SH 交联形成可注射的水凝胶系统。该系统释放的 TP 和羧基-PTIO 可通过类似的信号通路有效防止软骨炎症和损伤。总之，所提出的系统为治疗 OA 提供了一种有效的方法。

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引用次数: 0

Influence of magnesium addition on microstructural and mechanical stability of hydrostatically extruded biodegradable zinc alloys 加镁对静水挤压可生物降解锌合金微观结构和机械稳定性的影响

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-10-10 DOI: 10.1016/j.bioactmat.2024.09.028

Magdalena Gieleciak , Anna Jarzębska , Łukasz Maj , Paweł Petrzak , Mariusz Kulczyk , Łukasz Rogal , Magdalena Bieda

Pure and low-alloy zinc holds significant potential for use in biodegradable devices, such as coronary stents. However, its thermal stability has not yet been thoroughly characterized. This study focuses on the effect of magnesium addition on the mechanical and microstructural stability of zinc alloys with 0.6 and 1.3 wt% Mg, subjected to hot extrusion and hydrostatic extrusion. Pure zinc was used as a reference material to provide a comprehensive comparison. Electron Backscatter Diffraction (EBSD) analysis revealed that the addition of magnesium enhanced thermal stability by forming intermetallic Mg₂Zn₁₁ phases, that hindered grain growth as compared with pure zinc. The Zn-0.6 Mg alloy exhibited faster static recrystallization compared to the Zn-1.3 Mg alloy, attributed to its lower initial average grain size and higher density of low-angle grain boundaries. These microstructural changes correlated with mechanical properties, as all materials showed increased strength after heating to 50 °C, which was attributed to dislocation annihilation and the formation of low-angle grain boundaries, as observed through transmission electron microscopy (TEM). Static compression tests demonstrated that the Zn-1.3 Mg alloy maintained a high compressive yield strength of ≈350 MPa, even after heating to 150 °C, highlighting its potential for safe future processing into stents.

纯锌和低合金锌在冠状动脉支架等可生物降解装置中的应用潜力巨大。然而，它的热稳定性尚未得到彻底研究。本研究的重点是在热挤压和静压挤压过程中，添加镁对含镁量为 0.6 和 1.3 wt% 的锌合金的机械和微观结构稳定性的影响。纯锌被用作参考材料，以便进行全面比较。电子反向散射衍射（EBSD）分析表明，与纯锌相比，镁的添加通过形成金属间 Mg2Zn11 相来提高热稳定性，从而阻碍晶粒的生长。与 Zn-1.3 Mg 合金相比，Zn-0.6 Mg 合金的静态再结晶速度更快，这归因于其较低的初始平均晶粒尺寸和较高的低角度晶界密度。通过透射电子显微镜（TEM）观察，这些微观结构变化与机械性能相关，因为所有材料在加热到 50 °C 后强度都有所提高，这归因于位错湮灭和低角度晶界的形成。静态压缩测试表明，Zn-1.3 Mg 合金即使在加热到 150 ℃ 后仍能保持≈350 兆帕的高压缩屈服强度，这突出表明它具有在未来安全加工成支架的潜力。

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引用次数: 0

Readily constructed squaraine J-aggregates with an 86.0 % photothermal conversion efficiency for photothermal therapy 用于光热疗法的光热转换效率高达 86.0 % 的简易方碱 J-聚合体

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-10-10 DOI: 10.1016/j.bioactmat.2024.09.031

Xin Xie , Yafang Dong , Yuan Zhang , Zongliang Xie , Xinsheng Peng , Yong Huang , Wei Yang , Bowen Li , Qiqing Zhang

The development of photothermal agents with high photothermal conversion efficiency (PCE) and long absorption wavelengths is crucial for safe and effective anti-cancer treatment. However, achieving these advantages often requires precise molecular design and complex synthetic procedures. In this study, we present a simple, precise, and effective method for fabricating photothermal agents with high PCE using long wavelength excitation. This approach involves linking two electron-donating components, diphenylamine (DPA), and an electron-withdrawing squaraine (SQ), via a π-bridge thiophene (T). The resulting D-π-A-π-D structure leads to a red-shifted absorption band. Within the DTS structure, DPA functions as a molecular rotor, T serves as a coplanar backbone, and SQ promotes J aggregation. When DTS nanoparticles (NPs) are fabricated using an amphiphilic nano-carrier, the maximum absorption wavelength shifts from 701 to 803 nm. This shift is accompanied by reduced fluorescence and an exceptionally high PCE of 86.0 %. Both in vitro and in vivo assessments confirm that DTS NPs exhibit strong potential for photothermal antitumor therapy. Overall, this strategy offers a valuable framework for designing photothermal agents with clinical applications in mind, offering a simpler and more efficient approach to achieving high PCE and long absorption wavelengths.

开发具有高光热转换效率（PCE）和长吸收波长的光热制剂对于安全有效的抗癌治疗至关重要。然而，要实现这些优势往往需要精确的分子设计和复杂的合成过程。在本研究中，我们提出了一种简单、精确、有效的方法，利用长波长激发来制造具有高 PCE 的光热制剂。这种方法包括通过π桥噻吩（T）连接两个电子捐献成分--二苯胺（DPA）和一个电子吸收方碱（SQ）。由此产生的 D-π-A-π-D 结构导致了红移吸收带。在 DTS 结构中，DPA 起着分子转子的作用，T 起着共面骨架的作用，而 SQ 则促进 J 的聚集。当使用两亲性纳米载体制造 DTS 纳米粒子（NPs）时，最大吸收波长从 701 纳米变为 803 纳米。这种转变伴随着荧光的减少和 86.0 % 的超高 PCE。体外和体内评估都证实，DTS NPs 在光热抗肿瘤治疗方面具有很强的潜力。总之，这种策略为设计具有临床应用价值的光热制剂提供了一个宝贵的框架，为实现高 PCE 和长吸收波长提供了一种更简单、更有效的方法。

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引用次数: 0

Injectable double-crosslinked bone cement with enhanced bone adhesion and improved osteoporotic pathophysiological microenvironment for osteoregeneration in osteoporosis 具有增强骨粘附性和改善骨质疏松症病理生理微环境的可注射双交联骨水泥，用于骨质疏松症的骨再生

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-10-02 DOI: 10.1016/j.bioactmat.2024.09.032

Lingfei Zhao , Chenyu Liu , Xing Chen , Zirui He , Shuiquan Zhang , Anan Zhang , Shuaimin Tang , Zihan Wu , Changsheng Liu , Yuan Yuan

The osteoporotic bone defect caused by excessive activity of osteoclasts has posed a challenge for public healthcare. However, most existing bioinert bone cement fails to effectively regulate the pathological bone microenvironment and reconstruct bone homeostasis in the presence of osteoclast overactivity and osteoblast suppression. Herein, inspired by natural bone tissue, an in-situ modulation system for osteoporotic bone regeneration is developed by fabricating an injectable double-crosslinked PEGylated poly(glycerol sebacate) (PEGS)/calcium phosphate cement (CPC) loaded with sodium alendronate (ALN) (PEGS/CPC@ALN) adhesive bone cement. By incorporating ALN, the organic-inorganic interconnection within PEGS/CPC@ALN results in a 100 % increase in compression modulus and energy dissipation efficiency. Additionally, PEGS/CPC@ALN effectively adheres to the bone by bonding with amine and calcium ions present on the bone surface. Moreover, this in-situ regulation system comprehensively mitigates excessive bone resorption through the buffering effect of CPC to improve the acidic microenvironment of osteoporotic bone and the release of ALN to inhibit hyperactive osteoclasts, and facilitates stem cell proliferation and differentiation into osteoblasts through calcium ion release. Overall, the PEGS/CPC@ALN effectively regulates the pathological microenvironment of osteoporosis while promoting bone regeneration through synergistic effects of drugs and materials, thereby improving bone homeostasis and enabling minimally invasive treatment for osteoporotic defects.

破骨细胞过度活跃导致的骨质疏松性骨缺损已成为公共医疗保健的一大挑战。然而，现有的生物惰性骨水泥大多无法在破骨细胞过度活跃和成骨细胞受到抑制的情况下，有效调节病态骨微环境，重建骨平衡。本文受天然骨组织的启发，通过制造一种可注射的双交联聚癸二酸甘油酯（PEGS）/磷酸钙骨水泥（CPC）负载阿仑膦酸钠（ALN）（PEGS/CPC@ALN）粘接骨水泥，开发了一种用于骨质疏松性骨再生的原位调节系统。通过加入 ALN，PEGS/CPC@ALN 中的有机-无机互连使压缩模量和能量耗散效率提高了 100%。此外，PEGS/CPC@ALN 还能与骨表面的胺和钙离子结合，从而有效地粘附在骨上。此外，这种原位调节系统通过 CPC 的缓冲作用改善骨质疏松骨的酸性微环境，通过释放 ALN 抑制亢进的破骨细胞，从而全面缓解骨的过度吸收，并通过释放钙离子促进干细胞增殖和分化成成骨细胞。总之，PEGS/CPC@ALN 可有效调节骨质疏松症的病理微环境，同时通过药物和材料的协同作用促进骨再生，从而改善骨平衡，实现骨质疏松症缺损的微创治疗。

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引用次数: 0

Inhalable and bioactive lipid-nanomedicine based on bergapten for targeted acute lung injury therapy via orchestrating macrophage polarization 基于贝加肽的可吸入生物活性脂质纳米药物通过协调巨噬细胞极化实现急性肺损伤靶向治疗

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-10-01 DOI: 10.1016/j.bioactmat.2024.09.020

Ran Liao , Zhi-Chao Sun , Liying Wang , Caihong Xian , Ran Lin , Guifeng Zhuo , Haiyan Wang , Yifei Fang , Yuntao Liu , Rongyuan Yang , Jun Wu , Zhongde Zhang

Acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome, is a life-threatening disease closely associated with an imbalance of M1/M2 macrophage polarization. However, current therapeutic strategies for ALI are controversial due to their side effects, restricted administration routes, or poor targeted delivery. The development of herbal medicine has uncovered numerous anti-inflammatory compounds potentially beneficial for ALI therapy. One such compound is the bergapten, a coumarin, which has been isolated from Ficus simplicissima Lour. However, it's been used as an anti-cancer drug and it's effects on ALI remain unexplored. The poor solubility and biodistribution of bergapten heavily limit its application. In this timely report, we developed a bioactive and lung-targeting lipid-nanomedicine by integrating bergapten and DPPC liposome, named as Ber-lipo. A comprehensive series of in vitro experiments confirmed the anti-inflammatory effects of Ber-lipo and its protective roles in maintaining the homeostasis of macrophage polarization and epithelial–endothelial integrity. In a lipopolysaccharide (LPS)-induced ALI mouse model, Ber-lipo can target inflamed lungs and significantly improve lung edema, tissue injury, and pulmonary function, relieve body weight loss, pulmonary permeability, and proinflammatory status, and especially maintain a balance of M1/M2 macrophage polarization. Furthermore, RNA sequencing analysis showed Ber-lipo's potential in effectively treating inflammatory lung diseases such as pneumonia, inhibiting proinflammatory signals, and altering the transcriptome of M1/M2 macrophages-associated genes in lung tissues. Molecular docking and Western blot analyses validated that Ber-lipo suppressed the activation of the TLR4/MyD88/NF-κB signaling axis responsible for ALI progression. In conclusion, this study demonstrates for the first time that new inhalable nanomedicine (Ber-lipo) can target inflamed lungs and ameliorates ALI by reprogramming macrophage polarization to an anti-inflammatory state via inactivating the TLR4/MyD88/NF-κB pathway, hence providing a promising strategy for enhanced ALI therapy in the clinic.

急性肺损伤（ALI）或更严重的急性呼吸窘迫综合征是一种危及生命的疾病，与 M1/M2 巨噬细胞极化失衡密切相关。然而，由于副作用、给药途径受限或靶向性差等原因，目前针对 ALI 的治疗策略存在争议。中草药的发展发现了许多可能有益于 ALI 治疗的抗炎化合物。其中一种化合物是从榕树中分离出来的香豆素--bergapten。不过，它一直被用作抗癌药物，对 ALI 的作用仍有待探索。bergapten 的溶解性和生物分布较差，严重限制了它的应用。在这篇及时的报告中，我们通过整合bergapten和DPPC脂质体，开发出了一种具有生物活性的肺靶向脂质纳米药物，命名为Ber-lipo。一系列全面的体外实验证实了 Ber-lipo 的抗炎作用及其在维持巨噬细胞极化平衡和上皮-内皮完整性方面的保护作用。在脂多糖（LPS）诱导的 ALI 小鼠模型中，Ber-lipo 可以靶向炎症肺，显著改善肺水肿、组织损伤和肺功能，减轻体重下降、肺通透性和促炎状态，尤其是维持 M1/M2 巨噬细胞极化的平衡。此外，RNA 测序分析表明 Ber-lipo 可有效治疗肺炎等肺部炎症性疾病，抑制促炎信号，改变肺组织中 M1/M2 巨噬细胞相关基因的转录组。分子对接和 Western 印迹分析验证了 Ber-lipo 可抑制导致 ALI 进展的 TLR4/MyD88/NF-κB 信号轴的激活。总之，本研究首次证明了新型可吸入纳米药物（Ber-lipo）可以靶向发炎的肺部，并通过灭活TLR4/MyD88/NF-κB通路将巨噬细胞极化重编程为抗炎状态来改善ALI，从而为临床上加强ALI治疗提供了一种前景广阔的策略。

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引用次数: 0

Hydrogel microsphere stem cell encapsulation enhances cardiomyocyte differentiation and functionality in scalable suspension system 水凝胶微球干细胞封装技术在可扩展的悬浮系统中增强了心肌细胞的分化和功能性

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-10-01 DOI: 10.1016/j.bioactmat.2024.08.043

Mohammadjafar Hashemi , Ferdous B. Finklea , Hanna Hammons , Yuan Tian , Nathan Young , Emma Kim , Caroline Halloin , Wiebke Triebert , Robert Zweigerdt , Amit Kumar Mitra , Elizabeth A. Lipke

A reliable suspension-based platform for scaling engineered cardiac tissue (ECT) production from human induced pluripotent stem cells (hiPSCs) is crucial for regenerative therapies. Here, we compared the production and functionality of ECTs formed using our scaffold-based, engineered tissue microsphere differentiation approach with those formed using the prevalent scaffold-free aggregate platform. We utilized a microfluidic system for the rapid (1 million cells/min), high density (30, 40, 60 million cells/ml) encapsulation of hiPSCs within PEG-fibrinogen hydrogel microspheres. HiPSC-laden microspheres and aggregates underwent suspension-based cardiac differentiation in chemically defined media. In comparison to aggregates, microspheres maintained consistent size and shape initially, over time, and within and between batches. Initial size and shape coefficients of variation for microspheres were eight and three times lower, respectively, compared to aggregates. On day 10, microsphere cardiomyocyte (CM) content was 27 % higher and the number of CMs per initial hiPSC was 250 % higher than in aggregates. Contraction and relaxation velocities of microspheres were four and nine times higher than those of aggregates, respectively. Microsphere contractile functionality also improved with culture time, whereas aggregate functionality remained unchanged. Additionally, microspheres displayed improved β-adrenergic signaling responsiveness and uniform calcium transient propagation. Transcriptomic analysis revealed that while both microspheres and aggregates demonstrated similar gene regulation patterns associated with cardiomyocyte differentiation, heart development, cardiac muscle contraction, and sarcomere organization, the microspheres exhibited more pronounced transcriptional changes over time. Taken together, these results highlight the capability of the microsphere platform for scaling up biomanufacturing of ECTs in a suspension-based culture platform.

利用人体诱导多能干细胞（hiPSCs）生产工程化心脏组织（ECT）的可靠悬浮平台对再生疗法至关重要。在这里，我们比较了使用我们基于支架的工程组织微球分化方法和使用流行的无支架聚合平台形成的 ECT 的生产和功能。我们利用微流控系统将 hiPSCs 快速（100 万个细胞/分钟）、高密度（3000、4000、6000 万个细胞/毫升）封装在 PEG 纤维蛋白原水凝胶微球中。装载 HiPSC 的微球和聚集体在化学定义的培养基中进行了悬浮心脏分化。与聚集体相比，微球在最初、随着时间的推移、批次内和批次间都能保持一致的大小和形状。与聚集体相比，微球的初始尺寸和形状变异系数分别低八倍和三倍。在第 10 天，微球心肌细胞（CM）含量比聚集体高 27%，每个初始 hiPSC 的 CM 数量比聚集体高 250%。微球的收缩和松弛速度分别是聚集体的四倍和九倍。微球的收缩功能也随着培养时间的延长而提高，而聚集体的功能则保持不变。此外，微球显示出更好的β肾上腺素能信号反应性和均匀的钙瞬态传播。转录组分析表明，虽然微球和聚集体都表现出与心肌细胞分化、心脏发育、心肌收缩和肌节组织相关的类似基因调控模式，但随着时间的推移，微球表现出更明显的转录变化。综上所述，这些结果凸显了微球平台在悬浮培养平台中扩大 ECT 生物制造规模的能力。

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引用次数: 0

3D bioprinting of high-performance hydrogel with in-situ birth of stem cell spheroids 高性能水凝胶的三维生物打印与干细胞球体的原位诞生

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-09-29 DOI: 10.1016/j.bioactmat.2024.09.033

Shunyao Zhu , Xueyuan Liao , Yue Xu , Nazi Zhou , Yingzi Pan , Jinlin Song , Taijing Zheng , Lin Zhang , Liyun Bai , Yu Wang , Xia Zhou , Maling Gou , Jie Tao , Rui Liu

Digital light processing (DLP)-based bioprinting technology holds immense promise for the advancement of hydrogel constructs in biomedical applications. However, creating high-performance hydrogel constructs with this method is still a challenge, as it requires balancing the physicochemical properties of the matrix while also retaining the cellular activity of the encapsulated cells. Herein, we propose a facile and practical strategy for the 3D bioprinting of high-performance hydrogel constructs through the in-situ birth of stem cell spheroids. The strategy is achieved by loading the cell/dextran microdroplets within gelatin methacryloyl (GelMA) emulsion, where dextran functions as a decoy to capture and aggregate the cells for bioprinting while GelMA enables the mechanical support without losing the structural complexity and fidelity. Post-bioprinting, the leaching of dextran results in a smooth curved surface that promotes in-situ birth of spheroids within hydrogel constructs. This process significant enhances differentiation potential of encapsulated stem cells. As a proof-of-concept, we encapsulate dental pulp stem cells (DPSCs) within hydrogel constructs, showcasing their regenerative capabilities in dentin and neovascular-like structures in vivo. The strategy in our study enables high-performance hydrogel tissue construct fabrication with DLP-based bioprinting, which is anticipated to pave a promising way for diverse biomedical applications.

基于数字光处理（DLP）的生物打印技术为水凝胶构建体在生物医学领域的应用带来了巨大的发展前景。然而，用这种方法制造高性能的水凝胶构建体仍然是一项挑战，因为它要求在平衡基质的物理化学特性的同时，还能保持包裹细胞的细胞活性。在此，我们提出了一种简便实用的三维生物打印高性能水凝胶构建体的策略，即干细胞球体的原位诞生。该策略是通过在明胶甲基丙烯酰（GelMA）乳液中装载细胞/右旋糖酐微滴来实现的，其中右旋糖酐可作为诱饵捕获和聚集细胞以进行生物打印，而 GelMA 可在不损失结构复杂性和保真度的情况下提供机械支持。生物打印后，右旋糖酐的浸出会产生光滑的弧形表面，促进球体在水凝胶构建体中原位诞生。这一过程大大提高了封装干细胞的分化潜力。作为概念验证，我们将牙髓干细胞（DPSCs）封装在水凝胶构建物中，展示了它们在体内牙本质和新生血管样结构中的再生能力。我们的研究策略实现了基于 DLP 的生物打印技术的高性能水凝胶组织构建物制造，有望为各种生物医学应用铺平道路。

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引用次数: 0

Dexamethasone loaded DNA scavenger nanogel for systemic lupus erythematosus treatment 用于治疗系统性红斑狼疮的地塞米松负载 DNA 清除剂纳米凝胶

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-09-28 DOI: 10.1016/j.bioactmat.2024.08.030

Haofang Zhu , Danqing Huang , Min Nie , Yuanjin Zhao , Lingyun Sun

Lupus nephritis (LN) poses a severe risk for individuals with systemic lupus erythematosus (SLE), prompting extensive research into targeted delivery systems capable of modulating immune responses and clearing cell-free DNA (cfDNA). Here, we propose a novel renal homing nanogel that acts as a cfDNA scavenger and a dexamethasone (DXM) delivery carrier for LN treatment. Based on the generation 3 polylysine dendrimers, the created cationic nanogels (G3DSP) exhibit minimal toxicity and outstanding DXM loading efficiency. Our studies confirm that these nanogels can competitively bind with anionic cfDNA in vitro, leading to the suppression of toll-like receptor 9 (TLR9) activation. When administered systemically to MRL/lpr mice, the nanogels preferentially localize to and are retained in the inflamed kidneys, releasing their payload in response to reactive oxygen species (ROS), therefore effectively ameliorating SLE symptoms. Consequently, G3DSP nanogels emerge as a promising effective combined therapy for LN, minimizing cfDNA accumulation in vital organs and delivering immunomodulatory benefits through DXM.

狼疮性肾炎（LN）给系统性红斑狼疮（SLE）患者带来了严重的风险，促使人们对能够调节免疫反应和清除细胞游离 DNA（cfDNA）的靶向递送系统进行了广泛的研究。在这里，我们提出了一种新型肾归位纳米凝胶，它既是一种 cfDNA 清除剂，又是一种地塞米松（DXM）输送载体，可用于 LN 治疗。这种阳离子纳米凝胶（G3DSP）以第 3 代聚赖氨酸树枝状聚合物为基础，毒性极低，DXM 负载效率极高。我们的研究证实，这些纳米凝胶能在体外与阴离子 cfDNA 竞争性结合，从而抑制收费样受体 9（TLR9）的激活。当给 MRL/lpr 小鼠全身给药时，纳米凝胶会优先定位并保留在发炎的肾脏中，在活性氧（ROS）的作用下释放其有效载荷，从而有效改善系统性红斑狼疮的症状。因此，G3DSP 纳米凝胶有望成为治疗 LN 的一种有效的联合疗法，它能最大限度地减少 cfDNA 在重要器官中的积累，并通过 DXM 提供免疫调节益处。

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引用次数: 0

Corrigendum to “Mitochondria-engine with self-regulation to restore degenerated intervertebral disc cells via bioenergetic robust hydrogel design” [Bioact. Mater. 40C (2024) 1–18] 更正："具有自我调节功能的线粒体发动机通过生物能强健水凝胶设计恢复退化的椎间盘细胞" [Bioact. Mater. 40C (2024) 1-18]

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-09-28 DOI: 10.1016/j.bioactmat.2024.09.034

Juehan Wang, Yulin Jiang, Ce Zhu, Zheng Liu, Lin Qi, Hong Ding, Jing Wang, Yong Huang, Yubao Li, Yueming Song, Ganjun Feng, Li Zhang, Limin Liu

引用次数: 0