Regenerative Biomaterials最新文献_第9页

Mild Synthesis of Ultra-Bright Carbon Dots with Solvatochromism for Rapid Lipid Droplet Monitoring in Varied Physiological Process 温和合成具有溶解变色功能的超亮碳点，用于在各种生理过程中快速监测脂滴

IF 6.7 1区医学 Q1 MATERIALS SCIENCE, BIOMATERIALS

Regenerative Biomaterials

Pub Date : 2024-01-17 DOI: 10.1093/rb/rbad109

Borui Su, Dong Gao, Nini Xin, Kai Wu, Mei Yang, Shichao Jiang, Yusheng Zhang, Jie Ding, Chengheng Wu, Jing Sun, Dan Wei, Hongsong Fan, Zhenzhen Guo

Lipid droplets (LDs) participating in various cellular activities and are increasingly being emphasized. Fluorescence imaging Provides powerful tool for dynamic tracking of LDs, however, most current LDs probes remain inconsistent performance such as low Photoluminescence Quantum Yield (PLQY), poor photostability and tedious washing procedures. Herein, a novel yellow-emissive carbon dot (OT-CD) has been synthesized conveniently with high PLQY up to 90%. Besides, OT-CD exhibits remarkable amphiphilicity and solvatochromic property with lipid-water partition coefficient higher than 2, which is much higher than most LDs probes. These characters enable OT-CD high brightness, stable and wash-free LDs probing, and feasible for in vivo imaging. Then, detailed observation of LDs morphological and polarity variation dynamically in different cellular states were recorded, including ferroptosis and other diseases processes. Furthermore, fast whole imaging of zebrafish and identified LD enrichment in injured liver indicate its further feasibility for in vivo application. In contrast to the reported studies to date, this approach provides a versatile conventional synthesis system for high performance LDs targeting probes, combing the advantages of easy and high yield production, as well as robust brightness and stability for long-term imaging, facilitating investigations into organelle interactions and LD-associated diseases.

脂滴（LDs）参与各种细胞活动，并日益受到重视。荧光成像为动态追踪脂滴提供了强有力的工具，但目前大多数脂滴探针的性能仍不稳定，如光致发光量子产率（PLQY）低、光稳定性差和清洗过程繁琐。在此，我们方便地合成了一种新型黄色发射碳点（OT-CD），其光量子产率高达 90%。此外，OT-CD 还具有显著的两亲性和溶色性，其脂水分配系数大于 2，远高于大多数 LDs 探针。这些特性使得 OT-CD 具有高亮度、稳定和免清洗的 LDs 探测特性，可用于体内成像。随后，详细观察了 LDs 在不同细胞状态下的形态和极性动态变化，包括铁突变和其他疾病过程。此外，斑马鱼的快速整体成像和损伤肝脏中 LD 的富集也表明了其在体内应用的进一步可行性。与迄今报道的研究相比，该方法为高性能 LDs 靶向探针提供了一个多功能的常规合成系统，兼具生产简便、产量高、亮度强、稳定性好、可长期成像等优点，有助于研究细胞器相互作用和 LD 相关疾病。

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引用次数: 0

dECM restores macrophage immune homeostasis and alleviates iron overload to promote DTPI healing. dECM 可恢复巨噬细胞的免疫平衡，减轻铁超载，从而促进 DTPI 愈合。

IF 6.7 1区医学 Q1 MATERIALS SCIENCE, BIOMATERIALS

Regenerative Biomaterials

Pub Date : 2024-01-17 eCollection Date: 2024-01-01 DOI: 10.1093/rb/rbad118

Ju Zhang, Ruijuan Si, Yu Gao, Hui Shan, Qi Su, Zujian Feng, Pingsheng Huang, Deling Kong, Weiwei Wang

Due to its highly insidious and rapid progression, deep tissue pressure injury (DTPI) is a clinical challenge. Our previous study found that DTPI may be a skeletal muscle injury dominated by macrophage immune dysfunction due to excessive iron accumulation. Decellularized extracellular matrix (dECM) hydrogel promotes skeletal muscle injury repair. However, its role in polarizing macrophages and regulating iron metabolism in DTPI remains unclear. Here, porcine dECM hydrogel was prepared, and its therapeutic function and mechanism in repairing DTPI were investigated. The stimulus of dECM hydrogel toward RAW264.7 cells resulted in a significantly higher percentage of CD206⁺ macrophages and notably decreased intracellular divalent iron levels. In mice DTPI model, dECM hydrogel treatment promoted M1 to M2 macrophage conversion, improved iron metabolism and reduced oxidative stress in the early stage of DTPI. In the remodeling phase, the dECM hydrogel remarkably enhanced revascularization and accelerated skeletal muscle repair. Furthermore, the immunomodulation of dECM hydrogels in vivo was mainly involved in the P13k/Akt signaling pathway, as revealed by GO and KEGG pathway analysis, which may ameliorate the iron deposition and promote the healing of DTPI. Our findings indicate that dECM hydrogel is promising in skeletal muscle repair, inflammation resolution and tissue injury healing by effectively restoring macrophage immune homeostasis and normalizing iron metabolism.

深部组织压力损伤（DTPI）具有隐匿性强、进展迅速等特点，是一项临床难题。我们之前的研究发现，深部组织压力损伤可能是一种以巨噬细胞免疫功能失调为主的骨骼肌损伤，而巨噬细胞免疫功能失调是由于过量的铁积聚所致。脱细胞细胞外基质（dECM）水凝胶可促进骨骼肌损伤修复。然而，它在 DTPI 中极化巨噬细胞和调节铁代谢的作用仍不清楚。本文制备了猪 dECM 水凝胶，并研究了它在修复 DTPI 中的治疗功能和机制。dECM水凝胶刺激RAW264.7细胞后，CD206+巨噬细胞的比例显著增加，细胞内二价铁水平明显下降。在小鼠 DTPI 模型中，dECM 水凝胶处理可在 DTPI 早期促进 M1 向 M2 巨噬细胞转化，改善铁代谢并降低氧化应激。在重塑阶段，dECM 水凝胶显著增强了血管再通，加速了骨骼肌修复。此外，GO 和 KEGG 通路分析表明，dECM 水凝胶在体内的免疫调节作用主要涉及 P13k/Akt 信号通路，这可能会改善铁沉积并促进 DTPI 的愈合。我们的研究结果表明，dECM 水凝胶能有效恢复巨噬细胞的免疫稳态并使铁代谢正常化，在骨骼肌修复、炎症消退和组织损伤愈合方面具有广阔的前景。

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引用次数: 0

Fe-Zn alloy, a new biodegradable material capable of reducing ROS and inhibiting oxidative stress 能减少 ROS 和抑制氧化应激的新型可生物降解材料--铁锌合金

IF 6.7 1区医学 Q1 MATERIALS SCIENCE, BIOMATERIALS

Regenerative Biomaterials

Pub Date : 2024-01-13 DOI: 10.1093/rb/rbae002

Shuaikang Yang, Weiqiang Wang, Yanan Xu, Yonghui Yuan, Shengzhi Hao

Fe-based biodegradable materials have attracted significant attention due to their exceptional mechanical properties and favorable biocompatibility. Currently, research on Fe-based materials mainly focuses on regulating the degradation rate. However, excessive release of Fe ions during material degradation will induce the generation of reactive oxygen species (ROS), leading to oxidative stress and ferroptosis. Therefore, the control of ROS release and the improvement of biocompatibility for Fe-based materials are very important. In this study, new Fe-Zn alloys were prepared by electrodeposition with the intention of using Zn as an antioxidant to reduce oxidative damage during alloy degradation. Initially, the impact of three potential degradation ions (Fe2+, Fe3+, Zn2+) from the Fe-Zn alloy on human endothelial cells’ (ECs) activity and migration ability was investigated. Subsequently, cell adhesion, cell activity, ROS production, and DNA damage were assessed at various locations surrounding the alloy. Finally, the influence of different concentrations of Zn2+ in the medium on cell viability and ROS production was evaluated. High levels of ROS exhibited evident toxic effects on ECs and promoted DNA damage. As an antioxidant, Zn2+ effectively reduced ROS production around Fe and improved the cell viability on its surface at a concentration of 0.04 mmol/L. These findings demonstrate that Fe-Zn alloy can attenuate the ROS generated from Fe degradation thereby enhancing cytocompatibility.

铁基生物降解材料因其优异的机械性能和良好的生物相容性而备受关注。目前，有关铁基材料的研究主要集中在降解速率的调节上。然而，材料降解过程中铁离子的过度释放会诱发活性氧（ROS）的产生，从而导致氧化应激和铁变态反应。因此，控制 ROS 释放和改善铁基材料的生物相容性非常重要。本研究采用电沉积法制备了新型铁锌合金，目的是利用锌作为抗氧化剂来减少合金降解过程中的氧化损伤。首先，研究了铁锌合金中三种潜在降解离子（Fe2+、Fe3+、Zn2+）对人内皮细胞（ECs）活性和迁移能力的影响。随后，对合金周围不同位置的细胞粘附性、细胞活性、ROS 生成和 DNA 损伤进行了评估。最后，还评估了培养基中不同浓度的 Zn2+ 对细胞活力和 ROS 生成的影响。高浓度的 ROS 对心血管细胞有明显的毒性作用，并促进 DNA 损伤。作为一种抗氧化剂，当浓度为 0.04 mmol/L 时，Zn2+ 能有效减少铁周围的 ROS 生成，并提高铁表面的细胞活力。这些研究结果表明，铁-锌合金可以减少铁降解产生的 ROS，从而提高细胞相容性。

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引用次数: 0

Electrospun PCL/gelatin/arbutin nanofiber membranes as potent reactive oxygen species scavengers to accelerate cutaneous wound healing 电纺 PCL/明胶/熊果苷纳米纤维膜作为强效活性氧清除剂，可加速皮肤伤口愈合

IF 6.7 1区医学 Q1 MATERIALS SCIENCE, BIOMATERIALS

Regenerative Biomaterials

Pub Date : 2024-01-13 DOI: 10.1093/rb/rbad114

Mindong Du, Shuhan Liu, Nihan Lan, Ruiming Liang, Shengde Liang, Maoqiang Lan, Disen Feng, Li Zheng, Qingjun Wei, Ke Ma

The presence of excessive reactive oxygen species (ROS) at a skin wound site is an important factor affecting wound healing. ROS scavenging, which regulates the ROS microenvironment, is essential for wound healing. In this study, we used novel electrospun PCL/gelatin/arbutin(PCL/G/A) nanofibrous membranes as wound dressings, with PCL/gelatin(PCL/G) as the backbone, and plant-derived arbutin (hydroquinone-β-D-glucopyranoside, ARB) as an effective antioxidant that scavenges ROS and inhibits bacterial infection in wounds. The loading of ARB increased the mechanical strength of the nanofibres, with a water vapour transmission rate of more than 2500 g/(m2×24 h), and the water contact angle decreased, indicating that hydrophilicity and air permeability were significantly improved. Drug release and degradation experiments showed that the nanofibre membrane controlled the drug release and exhibited favourable degradability. Haemolysis experiments showed that the PCL/G/A nanofibre membranes were biocompatible, and DPPH and ABTS+ radical scavenging experiments indicated that PCL/G/A could effectively scavenge ROS to reflect the antioxidant activity. In addition, haemostasis experiments showed that PCL/G/A had good haemostatic effects in vitro and in vivo. In vivo animal wound closure and histological staining experiments demonstrated that PCL/G/A increased collagen deposition and remodelled epithelial tissue regeneration while showing good in vivo biocompatibility and non-toxicity. In conclusion, we successfully prepared a multifunctional wound dressing, PCL/G/A, for skin wound healing and investigated its potential role in wound healing, which is beneficial for the clinical translational application of phytomedicines.

皮肤伤口处存在过量活性氧（ROS）是影响伤口愈合的一个重要因素。清除 ROS 可调节 ROS 的微环境，对伤口愈合至关重要。本研究采用新型电纺 PCL/明胶/熊果苷（PCL/G/A）纳米纤维膜作为伤口敷料，以 PCL/明胶（PCL/G）为骨架，以植物提取的熊果苷（对苯二酚-β-D-吡喃葡萄糖苷，ARB）作为有效的抗氧化剂，清除 ROS 并抑制伤口细菌感染。ARB的负载增加了纳米纤维的机械强度，水蒸气透过率超过2500 g/(m2×24 h)，水接触角减小，表明亲水性和透气性得到显著改善。药物释放和降解实验表明，纳米纤维膜可控制药物释放，并表现出良好的降解性。溶血实验表明 PCL/G/A 纳米纤维膜具有良好的生物相容性，DPPH 和 ABTS+自由基清除实验表明 PCL/G/A 能有效清除 ROS，体现了其抗氧化活性。此外，止血实验表明，PCL/G/A 在体外和体内都具有良好的止血效果。体内动物伤口闭合和组织学染色实验表明，PCL/G/A 增加了胶原沉积，促进了上皮组织再生，同时在体内表现出良好的生物相容性和无毒性。总之，我们成功制备了一种用于皮肤伤口愈合的多功能伤口敷料 PCL/G/A，并研究了它在伤口愈合中的潜在作用，这有利于植物药的临床转化应用。

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引用次数: 0

Harnessing cytokine-induced killer cells to accelerate diabetic wound healing: an approach to regulating post-traumatic inflammation. 利用细胞因子诱导的杀伤细胞加速糖尿病伤口愈合：一种调节创伤后炎症的方法。

IF 6.7 1区医学 Q1 MATERIALS SCIENCE, BIOMATERIALS

Regenerative Biomaterials

Pub Date : 2024-01-09 eCollection Date: 2024-01-01 DOI: 10.1093/rb/rbad116

Yixi Yang, Cheng Zhang, Yuan Jiang, Yijun He, Jiawei Cai, Lin Liang, Zhaohuan Chen, Sicheng Pan, Chu Hua, Keke Wu, Le Wang, Zhiyong Zhang

Impaired immunohomeostasis in diabetic wounds prolongs inflammation and cytokine dysfunction, thus, delaying or preventing wound-surface healing. Extensive clinical studies have been conducted on cytokine-induced killer (CIK) cells recently, as they can be easily proliferated using a straightforward, inexpensive protocol. Therefore, the function of CIK cells in regulating inflammatory environments has been drawing attention for clinical management. Throughout the current investigation, we discovered the regenerative capacity of these cells in the challenging environment of wounds that heal poorly due to diabetes. We demonstrated that the intravenous injection of CIK cells can re-establish a proregenerative inflammatory microenvironment, promote vascularization and, ultimately, accelerate skin healing in diabetic mice. The results indicated that CIK cell treatment affects macrophage polarization and restores the function of regenerative cells under hyperglycemic conditions. This novel cellular therapy offers a promising intervention for clinical applications through specific inflammatory regulation functions.

糖尿病伤口的免疫稳态受损会延长炎症和细胞因子功能障碍的时间，从而延迟或阻止伤口表面的愈合。由于细胞因子诱导的杀伤细胞（CIK）可以用简单、廉价的方法轻松增殖，最近对其进行了广泛的临床研究。因此，CIK细胞在调节炎症环境中的功能一直备受临床关注。在本次研究中，我们发现了这些细胞在糖尿病导致伤口愈合不良的挑战性环境中的再生能力。我们证实，静脉注射 CIK 细胞可以重建有利于再生的炎症微环境，促进血管生成，最终加速糖尿病小鼠皮肤的愈合。结果表明，在高血糖条件下，CIK 细胞治疗会影响巨噬细胞的极化，并恢复再生细胞的功能。这种新型细胞疗法通过特定的炎症调节功能，为临床应用提供了一种前景广阔的干预手段。

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引用次数: 0

Construction of millimeter-scale vascularized engineered myocardial tissue using a mixed gel 利用混合凝胶构建毫米级血管化工程心肌组织

IF 6.7 1区医学 Q1 MATERIALS SCIENCE, BIOMATERIALS

Regenerative Biomaterials

Pub Date : 2023-12-28 DOI: 10.1093/rb/rbad117

Ming Ke, Wenhui Xu, Yansha Hao, Feiyang Zheng, Guanyuan Yang, Yonghong Fan, Fangfang Wang, Zhiqiang Nie, Chuhong Zhu

Engineering myocardium has shown great clinal potential for repairing permanent myocardial injury. However, the lack of perfusing blood vessels and difficulties in preparing a thick engineered myocardium result in its limited clinical use. We prepared a mixed gel containing fibrin (5 mg/mL) and collagen I (0.2 mg/mL), and verified that human umbilical vein endothelial cells (HUVECs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could form microvascular lumens and myocardial cell clusters by harnessing the low-hardness and hyperelastic characteristics of fibrin. hiPSC-CMs and HUVECs in the mixed gel formed self-organized cell clusters, which were then cultured in different media using a three-phase approach. The successfully constructed vascularized engineered myocardial tissue had a spherical structure and final diameter of 1–2 mm. The tissue exhibited autonomous beats that occurred at a frequency similar to a normal human heart rate. The internal microvascular lumen could be maintained for 6 weeks and showed good results during preliminary surface re-vascularization in vitro and vascular remodeling in vivo. In summary, we propose a simple method for constructing vascularized engineered myocardial tissue, through phased cultivation that does not rely on high-end manufacturing equipment and cutting-edge preparation techniques. The constructed tissue has potential value for clinical use after preliminary evaluation.

工程心肌在修复永久性心肌损伤方面显示出巨大的临床潜力。然而，由于缺乏灌注血管以及难以制备厚的工程心肌，其临床应用受到限制。我们制备了一种含有纤维蛋白（5 毫克/毫升）和胶原蛋白 I（0.2 毫克/毫升）的混合凝胶，并验证了人脐静脉内皮细胞（HUVECs）和人诱导多能干细胞衍生的心肌细胞（hiPSC-CMs）可以利用纤维蛋白的低硬度和高弹性特性形成微血管腔和心肌细胞簇。混合凝胶中的hiPSC-CMs和HUVEC形成自组织细胞簇，然后在不同的培养基中采用三相法进行培养。成功构建的血管化工程心肌组织具有球形结构，最终直径为 1-2 毫米。该组织能自主搏动，搏动频率与正常人的心率相似。内部微血管腔可维持 6 周，在体外初步表面再血管化和体内血管重塑过程中均显示出良好效果。总之，我们提出了一种通过分阶段培养构建血管化工程心肌组织的简单方法，这种方法不依赖于高端制造设备和尖端制备技术。经过初步评估，构建的组织具有潜在的临床应用价值。

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引用次数: 0

Immediate implantation of ultrafine fiber slow-release system based on cell electrospinning to induce osteogenesis of mesenchymal stem cells 基于细胞电纺丝的超细纤维缓释系统即时植入，诱导间充质干细胞成骨

IF 6.7 1区医学 Q1 MATERIALS SCIENCE, BIOMATERIALS

Regenerative Biomaterials

Pub Date : 2023-12-24 DOI: 10.1093/rb/rbad113

Tao Lu, Long Yang, Zhuo-yang Li, Yin Liu, Shun-en Xu, Chuan Ye

This study presents the development and evaluation of a P34HB ultrafine fiber slow-release system for in vivo osteogenic induction of Human Umbilical Cord Mesenchymal Stem Cells (HUCMSCs). Utilizing dual-nozzle and cell electrospinning techniques, the system encapsulates L-ascorbic acid-2-phosphate magnesium (ASP), β-glycerophosphate sodium (GP), and dexamethasone (DEX) within the fibers, ensuring sustained osteogenic differentiation. The scaffold's morphology, characterization, hydrophilicity, mechanical properties, and cellular behavior were examined. Immediate subcutaneous implantation in rabbits was conducted to observe its ectopic osteogenic induction effect. Successfully fabricated P34HB ultrafine fiber slow-release system. Characterization confirmed the uniform distribution of HUCMSCs and inducing components within the scaffold, with no chemical reactions affecting the active components. In vitro tests showcased a prolonged release of DEX and ASP, while biocompatibility assays highlighted the scaffold's suitability for cellular growth. Alizarin Red, Type I Collagen, and Osteopontin (OPN) staining verified the scaffold's potent osteogenic induction effect on HUCMSCs. Notably, immediate implantation into New Zealand white rabbits led to significant new bone formation within 8 weeks. These findings underscore the system's potential for immediate in vivo implantation without prior in vitro induction, marking a promising advancement in bone tissue engineering.

本研究介绍了用于体内诱导人脐间质干细胞（HUCMSCs）成骨的 P34HB 超细纤维缓释系统的开发和评估。该系统利用双喷嘴和细胞电纺技术，在纤维中封装了L-抗坏血酸-2-磷酸镁（ASP）、β-甘油磷酸钠（GP）和地塞米松（DEX），确保了持续的成骨分化。研究人员对支架的形态、特性、亲水性、机械性能和细胞行为进行了检测。在兔子皮下立即植入，观察其异位成骨诱导效果。成功制备了 P34HB 超细纤维缓释系统。表征证实，HUCMSCs 和诱导成分在支架内分布均匀，活性成分未受化学反应影响。体外测试表明，DEX 和 ASP 的释放时间延长，而生物相容性测试则强调了该支架对细胞生长的适用性。茜素红（Alizarin Red）、I 型胶原和骨生成素（Osteopontin，OPN）染色验证了该支架对 HUCMSCs 的强效成骨诱导作用。值得注意的是，立即植入新西兰白兔体内可在 8 周内形成大量新骨。这些发现强调了该系统无需事先进行体外诱导即可立即植入体内的潜力，标志着骨组织工程学取得了令人鼓舞的进展。

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引用次数: 0

Recent progress in functional metal organic frameworks for bio-medical application 用于生物医学的功能性金属有机框架的最新进展

IF 6.7 1区医学 Q1 MATERIALS SCIENCE, BIOMATERIALS

Regenerative Biomaterials

Pub Date : 2023-12-23 DOI: 10.1093/rb/rbad115

Wenwen Chai, Xiaochen Chen, Jing Liu, Liyan Zhang, Chunyu Liu, Li Li, Honiball John Robert, Haobo Pan, Xu Cui, Deping Wang

Metal-organic frameworks (MOFs) have a high specific surface area, adjustable pores and can be used to obtain functional porous materials with diverse and well-ordered structures through coordination and self-assembly, which has intrigued wide interest in a broad range of disciplines. In the arena of biomedical engineering, the functionalized modification of MOFs has produced drug carriers with excellent dispersion and functionalities such as target delivery and response release, with promising applications in bio-detection, disease therapy, tissue healing, and other areas. This review summarizes the present state of research on the functionalization of MOFs by physical binding or chemical cross-linking of small molecules, polymers, biomacromolecules, and hydrogels and evaluates the role and approach of MOFs functionalization in boosting the reactivity of materials. On this basis, research on the application of functionalized MOFs composites in biomedical engineering fields such as drug delivery, tissue repair, disease treatment, bio-detection and imaging is surveyed, and the development trend and application prospects of functionalized MOFs as an important new class of biomedical materials in the biomedical field are anticipated, which may provide some inspiration and reference for further development of MOF for bio-medical applications.

金属有机框架（MOFs）具有高比表面积和可调孔隙，可通过配位和自组装获得结构多样、有序的功能性多孔材料，这引起了众多学科的广泛兴趣。在生物医学工程领域，通过对 MOFs 进行功能化改性，已制备出具有良好分散性和靶向递送、响应释放等功能性的药物载体，在生物检测、疾病治疗、组织愈合等领域具有广阔的应用前景。本综述总结了通过小分子、聚合物、生物大分子和水凝胶的物理结合或化学交联实现 MOFs 功能化的研究现状，并评估了 MOFs 功能化在提高材料反应活性方面的作用和方法。在此基础上，考察了功能化 MOFs 复合材料在药物输送、组织修复、疾病治疗、生物检测和成像等生物医学工程领域的应用研究，展望了功能化 MOFs 作为一类重要的新型生物医学材料在生物医学领域的发展趋势和应用前景，为进一步开发 MOF 在生物医学领域的应用提供一些启示和借鉴。

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引用次数: 0

Fibrous topology promoted pBMP2-activated matrix on titanium implants boost osseointegration 钛种植体上的纤维拓扑结构促进了 pBMP2 激活基质的骨结合

IF 6.7 1区医学 Q1 MATERIALS SCIENCE, BIOMATERIALS

Regenerative Biomaterials

Pub Date : 2023-12-21 DOI: 10.1093/rb/rbad111

Ting He, Yichun Wang, Ruohan Wang, Huan Yang, Xueyi Hu, Yiyao Pu, Binbin Yang, Jingyuan Zhang, Juan Li, Chongxiang Huang, Rongrong Jin, Yu Nie, Xingdong Zhang

Titanium (Ti) implants have been extensively used after surgical operations. Its surface bioactivity is of importance to facilitate integration with surrounding bone tissue, and ultimately ensure stability and long-term functionality of the implant. The plasmid DNA-activated matrix (DAM) coating on the surface could benefit osseointegration but is still trapped by poor transfection for further application, especially on the bone marrow mesenchymal stem cells (BMSCs) in vivo practical conditions. Herein, we constructed a DAM on the surface of fibrous-grained titanium (FG Ti) composed of phase-transition lysozyme (P) as adhesive, cationic arginine-rich lipid (RLS) as the transfection agent, and plasmid DNA (pDNA) for bone morphology protein 2 (BMP-2) expression. The cationic lipid RLS improved up to 30-fold higher transfection than that of commercial reagents (Lipofectamine 2000 and polyethyleneimine) on MSC. And importantly, Ti surface topology not only promotes the DAM to achieve high transfection efficiency (∼75.7% positive cells) on MSC due to the favorable combination but also reserves its contact induction effect for osteoblasts. Upon further exploration, the fibrous topology on FG Ti could boost pDNA uptake for gene transfection, and cell migration in MSC through cytoskeleton remodeling and induce contact guidance for enhanced osteointegration. At the same time, the cationic RLS together with adhesive P were both antibacterial, showing up to 90% inhibition rate against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) with reduced adherent microorganisms and disrupted bacteria. Finally, the FG Ti-P/pBMP2 implant achieved accelerated bone healing capacities through highly efficient gene delivery, aligned surface topological structure, and increased antimicrobial properties in a rat femoral condylar defect model.

钛（Ti）植入物在外科手术后被广泛使用。其表面的生物活性对于促进与周围骨组织的整合，最终确保植入物的稳定性和长期功能性非常重要。表面的质粒 DNA 激活基质（DAM）涂层有利于骨结合，但在进一步应用中仍受困于转染效果不佳，尤其是在体内实际条件下对骨髓间充质干细胞（BMSCs）的影响。在此，我们在纤维颗粒钛（FG Ti）表面构建了一种 DAM，由相变溶菌酶（P）作为粘合剂、富含阳离子精氨酸的脂质（RLS）作为转染剂以及用于表达骨形态蛋白 2（BMP-2）的 DNA 质粒（pDNA）组成。与商用试剂（Lipofectamine 2000 和聚乙烯亚胺）相比，阳离子脂质 RLS 对间叶干细胞的转染效果提高了 30 倍。更重要的是，Ti 表面拓扑结构不仅能促进 DAM 在间充质干细胞上达到较高的转染效率（75.7% 的阳性细胞），还能保留其对成骨细胞的接触诱导作用。经进一步探讨，FG Ti 上的纤维拓扑结构可促进基因转染的 pDNA 摄取，并通过细胞骨架重塑促进间充质干细胞的细胞迁移，诱导接触引导以增强骨整合。同时，阳离子 RLS 和粘合剂 P 都具有抗菌作用，对大肠杆菌（E. coli）和金黄色葡萄球菌（S. aureus）的抑制率高达 90%，粘附的微生物减少，细菌被破坏。最后，在大鼠股骨髁突缺损模型中，FG Ti-P/pBMP2 植入物通过高效的基因传递、一致的表面拓扑结构和更强的抗菌性能，实现了加速骨愈合的能力。

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引用次数: 0

Precision cardiac targeting: empowering curcumin therapy through smart exosome-mediated drug delivery in myocardial infarction 精准的心脏靶向治疗：通过智能外泌体介导的心肌梗死药物输送增强姜黄素治疗的能力

IF 6.7 1区医学 Q1 MATERIALS SCIENCE, BIOMATERIALS

Regenerative Biomaterials

Pub Date : 2023-12-14 DOI: 10.1093/rb/rbad108

Ming Chen, Shengnan Wang, Yihuan Chen, Han Shen, Lei Chen, Liang Ding, Qingsong Tang, Ziying Yang, Weiqian Chen, Zhenya Shen

Nanoparticle-mediated drug delivery has emerged as a highly promising and effective therapeutic approach for addressing myocardial infarction. However, clinical translation tends to be a failure due to low cardiac retention as well as liver and spleen entrapment in previous therapies. Herein, we report a two-step exosome delivery system, which precludes internalization by the mononuclear phagocyte system before the delivery of therapeutic cardiac targeting exosomes (ExoCTP). Importantly, curcumin released by ExoCTP diminishes reactive oxygen species over-accumulation in ischemic myocardium, as well as serum levels of lactate dehydrogenase, malonyldialdehyde, superoxide dismutase, and glutathione, indicating better antioxidant capacity than free curcumin. Finally, our strategy was proven to greatly potentiate the delivery and therapeutic efficacy of curcumin without systemic toxicity. Taken together, our smart exosome-mediated drug delivery strategy can serve either as therapeutics alone or in combination with other drugs for effective heart targeting and subsequent wound healing.

纳米颗粒介导的药物输送已成为治疗心肌梗塞的一种极具前景的有效治疗方法。然而，由于以往疗法的心脏保留率低以及肝脏和脾脏夹带药物，临床转化往往失败。在此，我们报告了一种两步外泌体递送系统，该系统在递送治疗性心脏靶向外泌体（ExoCTP）之前排除了单核吞噬细胞系统的内化。重要的是，ExoCTP 释放的姜黄素能减少缺血心肌中活性氧的过度积累，并降低血清中乳酸脱氢酶、丙二醛、超氧化物歧化酶和谷胱甘肽的水平，这表明姜黄素的抗氧化能力优于游离姜黄素。最后，我们的策略被证明能大大提高姜黄素的递送和疗效，且无全身毒性。综上所述，我们的智能外泌体介导的药物递送策略既可以单独作为治疗药物，也可以与其他药物联合使用，从而有效地靶向心脏并促进伤口愈合。

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引用次数: 0