Bioactive Materials最新文献_第10页

Bioinspired conductive oriented nanofiber felt with efficient ROS clearance and anti-inflammation for inducing M2 macrophage polarization and accelerating spinal cord injury repair 生物启发导电定向纳米纤维毡具有有效的ROS清除和抗炎症诱导M2巨噬细胞极化和加速脊髓损伤修复。

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-12-13 DOI: 10.1016/j.bioactmat.2024.12.009

Qingxia Zhang , Jiahe Zheng , Linlong Li , Jui-Ming Yeh , Xianrui Xie , Yuqing Zhao , Chengbo Li , Guige Hou , Huanhuan Yan

Complete spinal cord injury (SCI) causes permanent locomotor, sensory and neurological dysfunctions. Targeting complex immunopathological microenvironment at SCI sites comprising inflammatory cytokines infiltration, oxidative stress and massive neuronal apoptosis, the conductive oriented nanofiber felt with efficient ROS clearance, anti-inflammatory effect and accelerating neural regeneration is constructed by step-growth addition polymerization and electrostatic spinning technique for SCI repair. The formation of innovative Fe³⁺-PDA-PAT chelate in nanofiber felt enhances hydrophilic, antioxidant, antibacterial, hemostatic and binding factor capacities, thereby regulating immune microenvironment of SCI. With the capabilities of up-regulating COX5A and STAT6 expressions, down-regulating the expressions of IL1β, CD36, p-ERK, NFκB2 and NFκB signaling pathway proteins, the nanofiber felt attenuates oxidative stress injury, promotes M2 macrophage polarization and down-regulates inflammatory response. After implantation into complete transection SCI rats, the nanofiber felt is revealed to recruit endogenous NSCs, induce the differentiation of NSCs into neurons while inhibit astrocytes formation and inflammation, reduces glia scar, and promotes angiogenesis, remyelination and neurological functional recovery. Overall, this innovative strategy provides a facile immune regulatory system to inhibit inflammatory response and accelerate nerve regeneration after SCI, and its targeted proteins and mechanisms are first elucidated, which holds great application promise in clinical treatment of complete SCI.

完全性脊髓损伤（SCI）会导致永久性的运动、感觉和神经功能障碍。针对脊髓损伤部位复杂的免疫病理微环境（包括炎症细胞因子浸润、氧化应激和大量神经元凋亡），通过阶跃生长加成聚合和静电纺丝技术构建了具有高效清除 ROS、抗炎和加速神经再生作用的导电定向纳米纤维毡，用于脊髓损伤修复。在纳米纤维毡中形成的创新型 Fe3+-PDA-PAT 螯合物增强了亲水、抗氧化、抗菌、止血和结合因子的能力，从而调节了 SCI 的免疫微环境。纳米纤维毡能上调 COX5A 和 STAT6 的表达，下调 IL1β、CD36、p-ERK、NFκB2 和 NFκB 信号通路蛋白的表达，从而减轻氧化应激损伤，促进 M2 巨噬细胞极化并下调炎症反应。将纳米纤维毡植入完全横断的 SCI 大鼠体内后，发现它能招募内源性 NSCs，诱导 NSCs 分化为神经元，同时抑制星形胶质细胞的形成和炎症反应，减少胶质瘢痕，促进血管生成、髓鞘再形成和神经功能恢复。总之，该创新策略提供了一种简便的免疫调节系统，可抑制炎症反应，加速脊髓损伤后的神经再生，并首次阐明了其靶向蛋白和机制，在完全性脊髓损伤的临床治疗中具有广阔的应用前景。

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引用次数: 0

TClC effectively suppresses the growth and metastasis of NSCLC via polypharmacology TClC通过多种药理作用有效抑制非小细胞肺癌的生长和转移。

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-12-13 DOI: 10.1016/j.bioactmat.2024.11.019

Jing Lu , Ying Zhang , Chunyan Yan , Jingwen Liu , Dan Qi , Yue Zhou , Qinwen Wang , Juechen Yang , Jing Jiang , Benhao Wu , Meiling Yang , Weiwei Zhang , Xin Zhang , Xiaoyu Shi , Yan Zhang , Kun Liu , Yongcai Liang , Chaoyang Wang , Hanyu Yang , Yuqing Gao , Guoying Zhang

Despite significant advances in targeted therapies and immunotherapies, non-small cell lung cancer (NSCLC) continues to present a global health challenge, with a modest five-year survival rate of 28 %, largely due to the emergence of treatment-resistant and metastatic tumors. In response, we synthesized a novel bioactive compound, ethyl 6-chlorocoumarin-3-carboxylyl L-theanine (TClC), which significantly inhibited NSCLC growth, epithelial mesenchymal transition (EMT), migration, and invasion in vitro and tumor growth and metastasis in vivo without inducing toxicity. TClC disrupts autocrine loops that promote tumor progression, particularly in stem-like CD133-positive NSCLC (CD133+ LC) cells, which are pivotal in tumor metastasis. Through targeted molecular assays, we identified direct binding targets of TClC, including Akt, NF-κB, β-catenin, EZH2, and PD-L1. This interaction not only suppresses the expression of oncogenic factors and cancer stem cell markers but also downregulates the expression of a multidrug resistance transporter, underscoring the compound's polypharmacological potential. These results position TClC as a promising candidate for NSCLC treatment, signaling a new era in the development of cancer therapies that directly target multiple critical cancer pathways.

尽管靶向治疗和免疫治疗取得了重大进展，但非小细胞肺癌（NSCLC）仍然是全球健康的挑战，其5年生存率为28%，主要是由于治疗耐药和转移性肿瘤的出现。为此，我们合成了一种新的生物活性化合物——乙基6-氯香豆素-3-羧基l -茶氨酸（TClC），该化合物在体外显著抑制非小细胞肺癌的生长、上皮间质转化（EMT）、迁移和侵袭以及体内肿瘤的生长和转移，且不产生毒性。TClC破坏促进肿瘤进展的自分泌环，特别是在干细胞样CD133阳性非小细胞肺癌（CD133+ LC）细胞中，这是肿瘤转移的关键。通过靶向分子检测，我们确定了TClC的直接结合靶点，包括Akt、NF-κB、β-catenin、EZH2和PD-L1。这种相互作用不仅抑制了致癌因子和癌症干细胞标记物的表达，还下调了多药耐药转运体的表达，强调了该化合物的多药理潜力。这些结果将TClC定位为NSCLC治疗的有希望的候选者，标志着直接靶向多种关键癌症途径的癌症治疗发展的新时代。

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引用次数: 0

Biomaterial scaffold stiffness influences the foreign body reaction, tissue stiffness, angiogenesis and neuroregeneration in spinal cord injury 生物材料支架刚度影响脊髓损伤后的异物反应、组织刚度、血管生成和神经再生。

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-12-12 DOI: 10.1016/j.bioactmat.2024.12.006

Yifeng Zheng , Maximilian Nützl , Thomas Schackel , Jing Chen , Norbert Weidner , Rainer Müller , Radhika Puttagunta

Biomaterial scaffold engineering presents great potential in promoting axonal regrowth after spinal cord injury (SCI), yet persistent challenges remain, including the surrounding host foreign body reaction and improper host-implant integration. Recent advances in mechanobiology spark interest in optimizing the mechanical properties of biomaterial scaffolds to alleviate the foreign body reaction and facilitate seamless integration. The impact of scaffold stiffness on injured spinal cords has not been thoroughly investigated. Herein, we introduce stiffness-varied alginate anisotropic capillary hydrogel scaffolds implanted into adult rat C5 spinal cords post-lateral hemisection. Four weeks post-implantation, scaffolds with a stiffness approaching that of the spinal cord effectively minimize the host foreign body reaction via yes-associated protein (YAP) nuclear translocation. Concurrently, the softest scaffolds maximize cell infiltration and angiogenesis, fostering significant axonal regrowth but limiting the rostral-caudal linear growth. Furthermore, as measured by atomic force microscopy (AFM), the surrounding spinal cord softens when in contact with the stiffest scaffold while maintaining a physiological level in contact with the softest one. In conclusion, our findings underscore the pivotal role of stiffness in scaffold engineering for SCI in vivo, paving the way for the optimal development of efficacious biomaterial scaffolds for tissue engineering in the central nervous system.

生物材料支架工程在促进脊髓损伤（SCI）后轴突再生方面具有巨大的潜力，但仍然存在持续的挑战，包括周围宿主异物反应和宿主-植入物不适当的整合。机械生物学的最新进展激发了人们对优化生物材料支架力学性能以减轻异物反应和促进无缝整合的兴趣。支架刚度对损伤脊髓的影响尚未得到充分的研究。在此，我们将不同刚度的海藻酸盐各向异性毛细血管水凝胶支架植入成年大鼠C5脊髓。植入后四周，刚度接近脊髓的支架通过yes-associated protein （YAP）核易位有效地减少了宿主异物反应。同时，最柔软的支架可以最大限度地促进细胞浸润和血管生成，促进轴突再生，但限制了喙端-尾端线性生长。此外，通过原子力显微镜（AFM）测量，当与最硬的支架接触时，周围的脊髓软化，而与最软的支架接触时保持生理水平。总之，我们的研究结果强调了刚度在活体脊髓损伤支架工程中的关键作用，为中枢神经系统组织工程中高效生物材料支架的优化开发铺平了道路。

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引用次数: 0

Novel carbon dots with dual Modulatory effects on the bone marrow and spleen as a potential therapeutic candidate for treating spinal cord injury 对骨髓和脾脏具有双重调节作用的新型碳点作为治疗脊髓损伤的潜在候选药物。

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-12-11 DOI: 10.1016/j.bioactmat.2024.11.032

Junjin Li , Hongda Wang , Yuanquan Li , Chunzhen Wang , Haiwen Feng , Yilin Pang , Jie Ren , Chuanhao Li , Erke Gao , Dejing Zhang , Dunxu Hu , Pengtian Zhao , Han Ding , Baoyou Fan , Tao Zhang , Xiaomeng Song , Zhijian Wei , Guangzhi Ning , Yong-Qiang Li , Shiqing Feng

Spinal cord injury triggers leukocyte mobilization from the peripheral circulation to the injury site, exacerbating spinal cord damage. Simultaneously, bone marrow hematopoietic stem cells (HSCs) and splenic leukocytes rapidly mobilize to replenish the depleted peripheral blood leukocyte pool. However, current treatments for spinal cord injuries overlook interventions targeting peripheral immune organs and tissues, highlighting the need to develop novel drugs capable of effectively regulating peripheral immunity and treating spinal cord injuries. In this study, we designed, synthesized, and characterized novel Ejiao carbon dots (EJCDs) that inhibit myeloid cell proliferation and peripheral migration by promoting HSC self-renewal, and distinct differentiation into erythroid progenitors in vitro and in vivo. Additionally, EJCDs attenuate the immune response in the spleen, leukocytes’ reservoir, following spinal cord injury by diminishing the local infiltration of monocytes and macrophages while promoting motor function recovery. These effects are mediated through the downregulation of CCAAT enhancer binding protein-β expression in the spleen and the upregulation of FZD4 protein expression in Lin⁻ Sca-1⁺ c-kit⁺ cells (LSKs) within the bone marrow. Our findings demonstrate that EJCDs effectively reduce myeloid cell infiltration post-spinal cord injury and promote neurological recovery, making them promising therapeutic candidates for treating spinal cord injuries.

脊髓损伤触发白细胞从外周循环动员到损伤部位，加剧脊髓损伤。同时，骨髓造血干细胞（hsc）和脾白细胞迅速调动，补充耗尽的外周血白细胞池。然而，目前脊髓损伤的治疗忽视了针对外周免疫器官和组织的干预措施，这突出了开发能够有效调节外周免疫和治疗脊髓损伤的新型药物的必要性。在这项研究中，我们设计、合成并表征了新型阿胶碳点（EJCDs），它通过促进HSC自我更新来抑制髓细胞增殖和外周迁移，并在体外和体内明显分化为红系祖细胞。此外，EJCDs通过减少局部单核细胞和巨噬细胞的浸润，从而减弱脊髓损伤后脾脏（白细胞储存库）的免疫反应，同时促进运动功能恢复。这些作用是通过下调脾脏中CCAAT增强子结合蛋白-β的表达和上调骨髓中Lin- Sca-1+ c-kit+细胞（lsk）中FZD4蛋白的表达来介导的。我们的研究结果表明，EJCDs可以有效地减少脊髓损伤后的髓细胞浸润，促进神经系统恢复，使其成为治疗脊髓损伤的有希望的治疗候选药物。

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引用次数: 0

Integrating melt electrospinning writing and microfluidics to engineer a human cardiac microenvironment for high-fidelity drug screening 整合熔体静电纺丝书写和微流体技术，设计用于高保真药物筛选的人类心脏微环境。

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-12-11 DOI: 10.1016/j.bioactmat.2024.11.037

Yu-hong Wang , Ting-ting Liu , Yan-ping Guo , Shuo-ji Zhu , Zi-ming Liao , Jia-mei Song , Xi-ming Zhu , Jia-liang Liang , Moussa Ide Nasser , Nan-bo Liu , De-hua Chang , Ping Zhu , Bin Yao

The preclinical evaluation of drug-induced cardiotoxicity is critical for developing novel drug, helping to avoid drug wastage and post-marketing withdrawal. Although human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and the engineered heart organoid have been used for drug screening and mimicking disease models, they are always limited by the immaturity and lack of functionality of the cardiomyocytes. In this study, we constructed a Cardiomyocytes-on-a-Chip (CoC) that combines micro-grooves (MGs) and circulating mechanical stimulation to recapitulate the well-organized structure and stable beating of myocardial tissue. The phenotypic changes and maturation of CMs cultured on the CoC have been verified and can be used for the evaluation of cardiotoxicity and cardioprotective drug responses. Taken together, these results highlight the ability of our myocardial microarray platform to accurately reflect clinical behaviour, underscoring its potential as a powerful pre-clinical tool for assessing drug response and toxicity.

药物性心脏毒性的临床前评价对新药开发至关重要，有助于避免药物浪费和上市后退出。虽然人类诱导多能干细胞衍生的心肌细胞（iPSC-CMs）和工程心脏类器官已被用于药物筛选和模拟疾病模型，但它们总是受到心肌细胞不成熟和缺乏功能的限制。在这项研究中，我们构建了一个心肌细胞芯片（CoC），它结合了微槽（mg）和循环机械刺激来重现心肌组织的有序结构和稳定跳动。在CoC上培养的CMs的表型变化和成熟已经得到验证，可用于评估心脏毒性和心脏保护药物反应。综上所述，这些结果突出了心肌微阵列平台准确反映临床行为的能力，强调了其作为评估药物反应和毒性的强大临床前工具的潜力。

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引用次数: 0

Copper–luteolin nanocomplexes for Mediating multifaceted regulation of oxidative stress, intestinal barrier, and gut microbiota in inflammatory bowel disease 铜-木犀草素纳米复合物在炎症性肠病中介导氧化应激、肠屏障和肠道微生物群的多方面调节。

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-12-11 DOI: 10.1016/j.bioactmat.2024.12.004

Wanyue Fu , Zhongshi Huang , Weiqi Li , Lingling Xu , Miaomiao Yang , Yan Ma , Hanghang Liu , Haisheng Qian , Wanni Wang

Oxidative stress, dysbiosis, and immune dysregulation have been confirmed to play pivotal roles in the complex pathogenesis of inflammatory bowel disease (IBD). Herein, we design copper ion–luteolin nanocomplexes (CuL NCs) through a metal–polyphenol coordination strategy, which plays a multifaceted role in the amelioration of IBD. The fabricated CuL NCs function as therapeutic agents with exceptional antioxidant and anti-inflammatory capabilities because of their great stability and capacity to scavenge reactive oxygen species (ROS). It can effectively modulate the inflammatory microenvironment including facilitating the efficient reduction of pro-inflammatory cytokine levels, protecting intestinal epithelial cells, promoting mucosal barrier repair and regulating intestinal microbiota. In addition, CuL NCs have been found to enhance cellular antioxidant and anti-inflammatory capacities by regulating the nuclear factor erythroid 2–related factor 2/heme oxygenase-1 (Nrf2/HO-1) oxidative stress pathway and nuclear factor kappa B (NF-κB) signaling pathway, respectively. Notably, CuL NCs demonstrate significant prophylactic and therapeutic efficacy in mouse models with typical IBD, including ulcerative colitis (UC) and Crohn's disease (CD). This study provides a new approach for building multifaceted therapeutic platforms for natural products to treat IBD.

氧化应激、菌群失调和免疫失调已被证实在炎症性肠病（IBD）复杂的发病机制中发挥着关键作用。在此，我们通过金属-多酚配位策略设计了铜离子-木犀草素纳米络合物（CuL NCs），它在改善 IBD 方面发挥着多方面的作用。所制备的 CuL NCs 具有极高的稳定性和清除活性氧（ROS）的能力，因此可作为具有卓越抗氧化和抗炎能力的治疗药物。它能有效调节炎症微环境，包括促进有效降低促炎细胞因子水平、保护肠上皮细胞、促进粘膜屏障修复和调节肠道微生物群。此外，研究还发现 CuL NCs 可分别通过调节核因子红细胞 2 相关因子 2/血红素氧合酶 1（Nrf2/HO-1）氧化应激途径和核因子卡巴 B（NF-κB）信号途径，增强细胞的抗氧化和抗炎能力。值得注意的是，CuL NCs 在溃疡性结肠炎（UC）和克罗恩病（CD）等典型 IBD 小鼠模型中显示出显著的预防和治疗效果。这项研究为建立天然产品治疗 IBD 的多元治疗平台提供了一种新方法。

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引用次数: 0

Lipidomic analysis of plant-derived extracellular vesicles for guidance of potential anti-cancer therapy 植物源性细胞外囊泡的脂质组学分析指导潜在的抗癌治疗。

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-12-10 DOI: 10.1016/j.bioactmat.2024.12.001

Fei Wang , Lanya Li , Junyao Deng , Jiacong Ai , Shushan Mo , Dandan Ding , Yingxian Xiao , Shiqi Hu , Dashuai Zhu , Qishan Li , Yan Zeng , Zhitong Chen , Ke Cheng , Zhenhua Li

Plant-derived extracellular vesicles (PEVs) have been regarded as a superior source for nanomedicine and drug delivery systems. Nevertheless, their clinical translation is hindered by the lack of clarity and even contradiction in their biomedical applications. Herein, we conducted a comprehensive compositional analysis of four commonly used PEVs to fully understand their functional lipid contents and assess their potential therapeutic applications. The lipidomic analysis revealed the presence of cytotoxic gingerols and shogaols in ginger-derived EVs (GEVs). Subsequent in vitro and in vivo investigations substantiated the remarkable tumor cell inhibitory and tumor growth suppression efficacy of GEVs. The transcriptomic analysis indicated that GEVs regulate the cell cycle and p53 signaling pathways, thereby inducing cancer cell apoptosis. The supplementary proteomic analysis suggested the potential protein markers in PEV research. These findings highlight the value of multi-omics analyses in elucidating the potential therapeutic effects of PEVs and in advancing the development of PEV-based therapies.

植物源性细胞外囊泡（PEVs）被认为是纳米医学和药物传递系统的优越来源。然而，由于其在生物医学应用中的不清晰甚至矛盾，它们的临床翻译受到阻碍。在此，我们对四种常用的pev进行了全面的成分分析，以充分了解其功能性脂质含量并评估其潜在的治疗应用。脂质组学分析显示，姜源性电动汽车（gev）中存在细胞毒性姜酚和姜酚。随后的体外和体内研究证实了转基因病毒显著的肿瘤细胞抑制和肿瘤生长抑制作用。转录组学分析表明，基因变异基因调控细胞周期和p53信号通路，从而诱导癌细胞凋亡。补充的蛋白质组学分析提示了PEV研究中潜在的蛋白质标记。这些发现突出了多组学分析在阐明pev的潜在治疗作用和推进基于pev的治疗方法的发展方面的价值。

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引用次数: 0

A deformable SIS/HA composite hydrogel coaxial scaffold promotes alveolar bone regeneration after tooth extraction 可变形SIS/HA复合水凝胶同轴支架促进拔牙后牙槽骨再生。

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-12-10 DOI: 10.1016/j.bioactmat.2024.12.008

Shiqing Ma , Yumeng Li , Shiyu Yao , Yucheng Shang , Rui Li , Lijuan Ling , Wei Fu , Pengfei Wei , Bo Zhao , Xuesong Zhang , Jiayin Deng

After tooth extraction, alveolar bone absorbs unevenly, leading to soft tissue collapse, which hinders full regeneration. Bone loss makes it harder to do dental implants and repairs. Inspired by the biological architecture of bone, a deformable SIS/HA (Small intestinal submucosa/Hydroxyapatite) composite hydrogel coaxial scaffold was designed to maintain bone volume in the socket. The SIS/HA scaffold containing GL13K as the outer layer, mimicking compact bone, while SIS hydrogel loaded with bone marrow mesenchymal stem cells-derived exosomes (BMSCs-Exos) was utilized as the inner core of the scaffolds, which are like soft tissue in the skeleton. This coaxial scaffold exhibited a modulus of elasticity of 0.82 MPa, enabling it to adaptively fill extraction sockets and maintain an osteogenic space. Concurrently, the inner layer of this composite scaffold, enriched with BMSCs-Exos, promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs) and BMSCs into the scaffold interior (≈3-fold to the control), up-regulated the expression of genes related to osteogenesis (BMP2, ALP, RUNX2, and OPN) and angiogenesis (HIF-1α and VEGF). This induced new blood vessels and bone growth within the scaffold, addressing the issue of low bone formation rates at the center of defects. GL13K was released by approximately 40.87 ± 4.37 % within the first three days, exerting a localized antibacterial effect and further promoting vascularization and new bone formation in peripheral regions. This design aims to achieve an all-around and efficient bone restoration effect in the extraction socket using coaxial scaffolds through a dual internal and external mechanism.

拔牙后，牙槽骨吸收不均匀，导致软组织塌陷，阻碍完全再生。骨质流失使得种植和修复牙齿变得更加困难。受骨的生物结构的启发，设计了一种可变形的SIS/HA（小肠粘膜下层/羟基磷灰石）复合水凝胶同轴支架来维持窝内的骨体积。以GL13K为外层的SIS/HA支架，模拟致密骨，以装载骨髓间充质干细胞衍生外泌体（BMSCs-Exos）的SIS水凝胶作为支架的内核，类似于骨骼中的软组织。该同轴支架的弹性模量为0.82 MPa，能够自适应填充拔牙槽并维持成骨空间。同时，该复合支架内层富集BMSCs- exos，促进人脐静脉内皮细胞（HUVECs）和BMSCs向支架内部的增殖和迁移（约为对照组的3倍），上调成骨相关基因（BMP2、ALP、RUNX2、OPN）和血管生成相关基因（HIF-1α、VEGF）的表达。这诱导了支架内的新血管和骨生长，解决了缺损中心骨形成率低的问题。GL13K在前三天释放约40.87±4.37%，发挥局部抗菌作用，并进一步促进外周区域血管化和新骨形成。本设计旨在通过内外双机制，利用同轴支架在拔牙槽内实现全面高效的骨修复效果。

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引用次数: 0

Enhancing bone regeneration through 3D printed biphasic calcium phosphate scaffolds featuring graded pore sizes 通过具有分级孔径的 3D 打印双相磷酸钙支架促进骨再生。

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-12-09 DOI: 10.1016/j.bioactmat.2024.11.024

Yue Wang , Yang Liu , Shangsi Chen , Ming-Fung Francis Siu , Chao Liu , Jiaming Bai , Min Wang

Human long bones exhibit pore size gradients with small pores in the exterior cortical bone and large pores in the interior cancellous bone. However, most current bone tissue engineering (BTE) scaffolds only have homogeneous porous structures that do not resemble the graded architectures of natural bones. Pore-size graded (PSG) scaffolds are attractive for BTE since they can provide biomimicking porous structures that may lead to enhanced bone tissue regeneration. In this study, uniform pore size scaffolds and PSG scaffolds were designed using the gyroid unit of triply periodic minimal surface (TPMS), with small pores (400 μm) in the periphery and large pores (400, 600, 800 or 1000 μm) in the center of BTE scaffolds (designated as 400-400, 400–600, 400–800, and 400–1000 scaffold, respectively). All scaffolds maintained the same porosity of 70 vol%. BTE scaffolds were subsequently fabricated through digital light processing (DLP) 3D printing with the use of biphasic calcium phosphate (BCP). The results showed that DLP 3D printing could produce PSG BCP scaffolds with high fidelity. The PSG BCP scaffolds possessed improved biocompatibility and mass transport properties as compared to uniform pore size BCP scaffolds. In particular, the 400–800 PSG scaffolds promoted osteogenesis in vitro and enhanced new bone formation and vascularization in vivo while they displayed favorable compressive properties and permeability. This study has revealed the importance of structural design and optimization of BTE scaffolds for achieving balanced mechanical, mass transport and biological performance for bone regeneration.

人类长骨呈现出孔隙大小梯度，外部皮质骨中有小孔，内部松质骨中有大孔。然而，目前大多数骨组织工程（BTE）支架只有均匀的多孔结构，与天然骨骼的分级结构并不相似。孔径分级（PSG）支架对骨组织工程很有吸引力，因为它们可以提供仿生多孔结构，从而提高骨组织再生能力。本研究利用三周期最小表面（TPMS）的陀螺单元设计了均匀孔径支架和 PSG 支架，小孔（400 μm）位于 BTE 支架的外围，大孔（400、600、800 或 1000 μm）位于 BTE 支架的中心（分别称为 400-400、400-600、400-800 和 400-1000 支架）。所有支架的孔隙率均为 70%。随后，使用双相磷酸钙（BCP）通过数字光处理（DLP）三维打印技术制作了 BTE 支架。结果表明，DLP 三维打印技术可以制作出高保真的 PSG BCP 支架。与均匀孔径的BCP支架相比，PSG BCP支架具有更好的生物相容性和质量传输特性。特别是，400-800 PSG 支架在体外促进了成骨，在体内增强了新骨形成和血管化，同时还显示出良好的抗压性能和渗透性。这项研究揭示了 BTE 支架的结构设计和优化对于实现骨再生的机械、质量传输和生物性能平衡的重要性。

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引用次数: 0

Evaluation of the interface of metallic-coated biodegradable polymeric stents with prokaryotic and eukaryotic cells 金属包覆生物可降解聚合物支架与原核和真核细胞界面的评价。

IF 18 1区医学 Q1 ENGINEERING, BIOMEDICAL

Bioactive Materials

Pub Date : 2024-12-09 DOI: 10.1016/j.bioactmat.2024.12.003

Ana M. Sousa , Rita Branco , Paula V. Morais , Manuel F. Pereira , Ana M. Amaro , Ana P. Piedade

Polymeric coronary stents, like the ABSORB™, are commonly used to treat atherosclerosis due to their bioresorbable and cell-compatible polymer structure. However, they face challenges such as high strut thickness, high elastic recoil, and lack of radiopacity. This study aims to address these limitations by modifying degradable stents produced by additive manufacturing with poly(lactic acid) (PLA) and poly(ε-caprolactone) (PCL) with degradable metallic coatings, specifically zinc (Zn) and magnesium (Mg), deposited via radiofrequency (rf) magnetron sputtering. The characterisation included the evaluation of the degradation of the coatings, antibacterial, anti-thrombogenicity, radiopacity, and mechanical properties.

The results showed that the metallic coatings inhibited bacterial growth, though Mg exhibited a high degradation rate. Thrombogenicity studies showed that Zn-coated stents had anticoagulant properties, while Mg-coated and controls were thrombogenic. Zn coatings significantly improved radiopacity, enhancing contrast by 43 %. Mechanical testing revealed that metallic coatings reduced yield strength and, thus, diminished elastic recoil after stent expansion. Zn-coated stents improved cyclic compression resistance by 270 % for PCL stents, with PLA-based stents showing smaller improvements. The coatings also enhanced crush resistance, particularly for Zn-coated PCL stents.

Overall, Zn-coated polymers have emerged as the premier prototype due to their superior biological and mechanical performance, appropriate degradation during the stent life, and ability to provide the appropriate radiopacity to medical devices.

聚合物冠状动脉支架，如吸收™，由于其生物可吸收和细胞兼容的聚合物结构，通常用于治疗动脉粥样硬化。然而，它们面临着诸如高支撑厚度、高弹性后坐力和缺乏放射性等挑战。本研究的目的是通过射频磁控溅射（rf）沉积可降解金属涂层，特别是锌（Zn）和镁（Mg），通过增材制造改性聚乳酸（PLA）和聚ε-己内酯（PCL）生产的可降解支架，以解决这些局限性。表征包括涂层的降解，抗菌，抗血栓性，不透光性和机械性能的评估。结果表明，金属涂层抑制细菌生长，但Mg的降解率较高。血栓形成性研究表明，锌涂层支架具有抗凝血性能，而镁涂层支架和对照组具有血栓形成性。锌涂层显著改善了透光性，对比度提高了43%。力学测试表明，金属涂层降低了屈服强度，从而减少了支架膨胀后的弹性后坐力。锌涂层支架将PCL支架的抗循环压缩能力提高了270%，而pla支架的改善幅度较小。该涂层还增强了抗挤压性，特别是对于镀锌PCL支架。总的来说，锌涂层聚合物由于其优越的生物和机械性能，在支架寿命期间适当的降解，以及为医疗设备提供适当的放射不透明度的能力，已经成为首要的原型。

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