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Intelligent nanocatalyst mediated lysosomal ablation pathway to coordinate the amplification of tumor treatment 智能纳米催化剂介导的溶酶体消融途径协调肿瘤治疗的放大效应
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-16 DOI: 10.1016/j.mtbio.2024.101299
Mingliang Pei , Xin Guan , De Zhao , Fan Yang , Yun Dong , Manxiu Huai , Wensong Ge , Xiaodong Hou , Wenfeng Chu , Kai Wang , Jie Chen , Huixiong Xu
The production of reactive oxygen species (ROS) is susceptible to external excitation or insufficient supply of related participants (e.g., hydrogen peroxide (H2O2) and sensitizer), liming ROS-driven tumor treatment. Additionally, the lysosomal retention effect severely hinders the utilization of ROS-based nanosystems and severely restricted the therapeutic effect of tumors. Therefore, first reported herein an intelligent nanocatalyst, TCPP-Cu@MnOx ((MnII)1(MnIII)2.1(MnIV)2.6O9.35), and proposed a programmed ROS amplification strategy to treat tumors. Initially, the acidity-unlocked nanocatalyst was voluntarily triggered to generate abundant singlet oxygen (1O2) to mediate acid lysosomal ablation to assist nanocatalyst escape and partially induce lysosomal death, a stage known as lysosome-driven therapy. More unexpectedly, the high-yielding production of 1O2 in acid condition (pH 5.0) was showed compared to neutral media (pH 7.4), with a difference of about 204 times between the two. Subsequently, the escaping nanocatalyst further activated H2O2-mediated 1O2 and hydroxyl radical (•OH) generation and glutathione (GSH) consumption for further accentuation tumor therapy efficiency, which is based on the Fenton-like reaction and Russell reaction mechanisms. Therefore, in this system, a program-activatable TCPP-Cu@MnOx nanocatalyst, was proposed to efficiently destruct organelle-lysosome via 1O2 inducing, and stimulated H2O2 conversion into highly toxic 1O2 and •OH in cytoplasm, constituting an attractive method to overcome limitations of current ROS treatment.
活性氧(ROS)的产生易受外部激发或相关参与者(如过氧化氢(H2O2)和敏化剂)供应不足的影响,从而限制了 ROS 驱动的肿瘤治疗。此外,溶酶体滞留效应严重阻碍了基于 ROS 的纳米系统的利用,严重制约了肿瘤的治疗效果。因此,本文首次报道了一种智能纳米催化剂TCPP-Cu@MnOx((MnII)1(MnIII)2.1(MnIV)2.6O9.35),并提出了一种治疗肿瘤的程序化ROS放大策略。最初,酸性解锁纳米催化剂被主动触发,产生大量单线态氧(1O2),介导酸性溶酶体消融,以帮助纳米催化剂逃逸并部分诱导溶酶体死亡,这一阶段被称为溶酶体驱动疗法。更令人意想不到的是,与中性介质(pH 7.4)相比,酸性条件(pH 5.0)下的 1O2 产量更高,两者相差约 204 倍。随后,逸出的纳米催化剂进一步激活了 H2O2- 介导的 1O2 和羟基自由基(-OH)的生成以及谷胱甘肽(GSH)的消耗,从而进一步提高了肿瘤治疗的效率。因此,在该系统中,提出了一种可程序激活的 TCPP-Cu@MnOx 纳米催化剂,通过诱导 1O2 高效破坏细胞器-溶酶体,并刺激细胞质中的 H2O2 转化为高毒性的 1O2 和 -OH,为克服目前 ROS 治疗的局限性提供了一种有吸引力的方法。
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引用次数: 0
Injectable hydrogels for Fenton-like Mn2+/Fe2+ delivery with enhanced chemodynamic therapy prevent osteosarcoma recurrence and promote wound healing after excision surgery 用于 Fenton 类 Mn2+/Fe2+ 递送的可注射水凝胶可增强化学动力疗法,防止骨肉瘤复发并促进切除手术后的伤口愈合
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-11 DOI: 10.1016/j.mtbio.2024.101297
Lutong Wang , Haoyu Guo , Weiyue Zhang , Xingyin Li , Ziliang Su , Xin Huang
Local recurrence of osteosarcoma and wound healing after excision surgery are major challenges in clinical research. The present anti-tumor treatments could inhibit normal tissues, resulting in difficulties in surgical wound healing. In this study, we constructed an injectable hydrogel as a platform to co-deliver MnO2 nanoparticles and ferrocene Fc, termed as (MnO2/Fc)@PLGA for osteosarcoma treatment and wound healing after excision. By simple local injection, the hydrogel could form a protective barrier on the surgical wound after osteosarcoma excision, which could promote wound healing and steady release of MnO2/Fc nanoparticles. The released MnO2/Fc might undergo the Fenton reaction through Mn2+/Fe2+ to inhibit osteosarcoma cells with chemodynamic therapy (CDT). Furthermore, MnO2 could catalyze endogenous H2O2 to produce O2, which eliminates the adverse effects of H2O2 and remodels the hypoxic state in the local lesions. The increased O2 facilitated surgical wound healing and anti-tumor effects by regulating the hypoxia inducible factor-1 functions. In conclusion, (MnO2/Fc)@PLGA hydrogel could effectively prevent local recurrence of osteosarcoma and promote wound healing after excision surgery, thereby providing a novel strategy for tumor treatment and tissue repair.
骨肉瘤的局部复发和切除手术后的伤口愈合是临床研究的主要难题。目前的抗肿瘤治疗可能会抑制正常组织,导致手术伤口难以愈合。在这项研究中,我们构建了一种可注射的水凝胶,作为共同递送 MnO2 纳米粒子和二茂铁 Fc 的平台,称为(MnO2/Fc)@PLGA,用于骨肉瘤的治疗和切除术后的伤口愈合。通过简单的局部注射,水凝胶可在骨肉瘤切除术后的手术伤口上形成保护屏障,促进伤口愈合和 MnO2/Fc 纳米粒子的稳定释放。释放出的 MnO2/Fc 可通过 Mn2+/Fe2+ 发生芬顿反应,以化学动力学疗法(CDT)抑制骨肉瘤细胞。此外,MnO2 还能催化内源性 H2O2 产生 O2,从而消除 H2O2 的不利影响,并重塑局部病灶的缺氧状态。增加的 O2 可通过调节缺氧诱导因子-1 的功能,促进手术伤口愈合和抗肿瘤作用。总之,(MnO2/Fc)@PLGA 水凝胶能有效防止骨肉瘤局部复发,促进切除手术后的伤口愈合,从而为肿瘤治疗和组织修复提供了一种新的策略。
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引用次数: 0
Innovative hydrogel-based therapies for ischemia-reperfusion injury: bridging the gap between pathophysiology and treatment 基于水凝胶的缺血再灌注损伤创新疗法:弥合病理生理学与治疗之间的差距
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-10 DOI: 10.1016/j.mtbio.2024.101295
Weibo Wang , Supeng Tai , Junyue Tao , Lexing Yang , Xi Cheng , Jun Zhou
Ischemia-reperfusion injury (IRI) commonly occurs in clinical settings, particularly in medical practices such as organ transplantation, cardiopulmonary resuscitation, and recovery from acute trauma, posing substantial challenges in clinical therapies. Current systemic therapies for IRI are limited by poor drug targeting, short efficacy, and significant side effects. Owing to their exceptional biocompatibility, biodegradability, excellent mechanical properties, targeting capabilities, controlled release potential, and properties mimicking the extracellular matrix (ECM), hydrogels not only serve as superior platforms for therapeutic substance delivery and retention, but also facilitate bioenvironment cultivation and cell recruitment, demonstrating significant potential in IRI treatment. This review explores the pathological processes of IRI and discusses the roles and therapeutic outcomes of various hydrogel systems. By categorizing hydrogel systems into depots delivering therapeutic agents, scaffolds encapsulating mesenchymal stem cells (MSCs), and ECM-mimicking hydrogels, this article emphasizes the selection of polymers and therapeutic substances, and details special crosslinking mechanisms and physicochemical properties, as well as summarizes the application of hydrogel systems for IRI treatment. Furthermore, it evaluates the limitations of current hydrogel treatments and suggests directions for future clinical applications.
缺血再灌注损伤(IRI)通常发生在临床环境中,尤其是在器官移植、心肺复苏和急性创伤恢复等医疗实践中,给临床治疗带来了巨大挑战。由于药物靶向性差、疗效短、副作用大,目前治疗 IRI 的全身疗法受到限制。由于水凝胶具有优异的生物相容性、生物可降解性、优良的机械性能、靶向性、控释潜力以及模仿细胞外基质(ECM)的特性,因此水凝胶不仅是输送和保留治疗物质的优良平台,还能促进生物环境培养和细胞招募,在 IRI 治疗中展现出巨大的潜力。本综述探讨了 IRI 的病理过程,并讨论了各种水凝胶系统的作用和治疗效果。通过将水凝胶系统分为输送治疗药物的储层、包裹间充质干细胞(MSCs)的支架和模拟 ECM 的水凝胶,本文强调了聚合物和治疗物质的选择,详细介绍了特殊的交联机制和理化性质,并总结了水凝胶系统在 IRI 治疗中的应用。此外,文章还评估了当前水凝胶疗法的局限性,并提出了未来临床应用的方向。
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引用次数: 0
ROS-scavenging ultrasonicated graphene oxide/alginate microgels for mesenchymal stem cell delivery and hindlimb ischemia treatment 清除 ROS 的超声氧化石墨烯/精氨酸微凝胶用于间充质干细胞输送和后肢缺血治疗
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-10 DOI: 10.1016/j.mtbio.2024.101289
Seungjun Lee , Goeun Choe , Jongdarm Yi , Junghyun Kim , Sun Hong Lee , Jin Jeon , Hee Seok Yang , Jae Young Lee
Mesenchymal stem cell (MSC) transplantation is widely recognized as a promising treatment for peripheral artery diseases because of their unique ability to secrete multiple growth factors and immunomodulatory cytokines. However, direct administration of MSCs frequently results in insufficient therapeutic efficacy due to low viability and poor retention at the implantation site. The delivery of MSCs in microsized hydrogels allows for simple injection, improved retention, and enhanced cell protection. However, the high oxidative stress present in ischemic tissues significantly impairs the viability and therapeutic activity of transplanted MSCs. This study aimed to develop a simple and effective method for fabricating reactive oxygen species (ROS)-scavenging microgels to enhance the MSC efficacy for ischemic hindlimb treatment. Specifically, tip-sonicated graphene oxide (GO)/alginate (sGO/alginate) microgels exhibited significantly increased antioxidizing activity against various ROS compared with pristine GO/alginate microgels. MSCs encapsulated in sGO/alginate microgels (MSC/sGO/alginate) demonstrated higher viability than those encapsulated in alginate or GO/alginate microgels under various oxidative stress conditions. Furthermore, human umbilical vein endothelial cells co-cultured with MSCs encapsulated in sGO/alginate microgels formed more tubes under both normal and H2O2-treated conditions, implying enhanced pro-angiogenic potential of the MSCs. In vivo experiments using hindlimb ischemia mouse models revealed significant improvements in blood perfusion, limb salvage, vascularization, and MSC survival in the MSC/sGO/alginate group compared with the other groups (MSC, MSC/alginate, and MSC/GO/alginate). The strategy developed in this study offers a straightforward and powerful method for treating various ROS-related diseases, including ischemia.
间充质干细胞(MSC)移植因其分泌多种生长因子和免疫调节细胞因子的独特能力而被广泛认为是治疗外周动脉疾病的一种有前途的方法。然而,由于间充质干细胞的存活率低且在植入部位的存留率低,直接给药往往导致疗效不佳。将间叶干细胞置于微小的水凝胶中可实现简单的注射、更好的保留和更强的细胞保护。然而,缺血组织中存在的高氧化应激会严重损害移植间充质干细胞的存活率和治疗活性。本研究旨在开发一种简单有效的活性氧(ROS)清除微凝胶制造方法,以提高间充质干细胞治疗缺血后肢的疗效。具体来说,与原始的氧化石墨烯/银杏酸盐微凝胶相比,尖端声化氧化石墨烯/银杏酸盐微凝胶对各种ROS的抗氧化活性明显提高。在各种氧化应激条件下,包裹在sGO/海藻酸盐微凝胶(MSC/sGO/海藻酸盐)中的间充质干细胞的存活率高于包裹在海藻酸盐或GO/海藻酸盐微凝胶中的间充质干细胞。此外,在正常和 H2O2 处理条件下,与包裹在 sGO/alginate 微凝胶中的间充质干细胞共同培养的人脐静脉内皮细胞形成了更多的血管,这意味着间充质干细胞的促血管生成潜能得到了增强。使用后肢缺血小鼠模型进行的体内实验显示,与其他组(间充质干细胞组、间充质干细胞/海藻酸盐组和间充质干细胞/GO/海藻酸盐组)相比,间充质干细胞/sGO/海藻酸盐组在血液灌注、肢体挽救、血管生成和间充质干细胞存活率方面都有显著改善。本研究开发的策略为治疗包括缺血在内的各种与 ROS 相关的疾病提供了一种简单而有效的方法。
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引用次数: 0
Biomimetic composite gelatin methacryloyl hydrogels for improving survival and osteogenesis of human adipose-derived stem cells in 3D microenvironment 仿生复合明胶甲基丙烯酰水凝胶用于提高人脂肪来源干细胞在三维微环境中的存活率和成骨率
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-09 DOI: 10.1016/j.mtbio.2024.101293
Eunhyung Kim , Jinkyu Lee , Se-Jeong Kim , Eun Mi Kim , Hayeon Byun , Seung Jae Huh , Eunjin Lee , Heungsoo Shin
Gelatin methacryloyl (GelMA) hydrogels are used for stem cell encapsulation in bone tissue engineering due to their fast and stable photo-crosslinking. However, cell viability and ability to induce osteogenesis are reduced by reactive oxygen species (ROS) produced during the crosslinking reaction. In this study, we developed biomimetic nanoparticles (TMNs) by combining tannic acid (TA) and simulated body fluid (SBF) minerals, and used them to synthesize GelMA-based composite hydrogels for addressing those limitations. The optimal concentrations of TA and SBF were investigated to create nanoparticles that can effectively scavenge ROS and induce osteogenesis. The incorporation of TMNs into composite hydrogels (G-TMN) significantly enhanced the survival and proliferation of encapsulated human adipose-derived stem cells (hADSCs) by providing resistance to oxidative conditions. In addition, the ions that were released, such as Ca2+ and PO43−, stimulated stem cell differentiation into bone cells. The hADSCs encapsulated in G-TMN had 2.0 ± 0.8-fold greater viability and 1.3 ± 1.8 times greater calcium deposition than those encapsulated in the hydrogel without nanoparticles. Furthermore, the in vivo transplantation of G-TMN into a subcutaneous mouse model demonstrated the rapid degradation of the gel-network while retaining the osteoinductive particles and cells in the transplanted area. The increased cellular activity observed in our multifunctional composite hydrogel can serve as a foundation for novel and effective therapies for bone deformities.
明胶甲基丙烯酰(GelMA)水凝胶因其快速稳定的光交联作用而被用于骨组织工程中的干细胞封装。然而,交联反应过程中产生的活性氧(ROS)会降低细胞活力和诱导骨生成的能力。在这项研究中,我们结合单宁酸(TA)和模拟体液(SBF)矿物质开发了仿生物纳米颗粒(TMNs),并用它们合成了基于 GelMA 的复合水凝胶,以解决这些局限性。研究了TA和SBF的最佳浓度,以制造出能有效清除ROS并诱导成骨的纳米颗粒。在复合水凝胶(G-TMN)中加入 TMN,可通过提供抗氧化能力显著提高包裹的人脂肪来源干细胞(hADSCs)的存活和增殖。此外,释放的离子(如 Ca2+ 和 PO43-)可刺激干细胞分化为骨细胞。与不含纳米颗粒的水凝胶相比,封装在G-TMN中的hADSCs活力高出2.0 ± 0.8倍,钙沉积量高出1.3 ± 1.8倍。此外,将 G-TMN 移植到小鼠皮下模型的体内试验表明,凝胶网络降解迅速,但骨诱导颗粒和细胞仍保留在移植区域。在我们的多功能复合水凝胶中观察到的细胞活性的提高,可以为新型、有效的骨畸形疗法奠定基础。
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引用次数: 0
Programmable biomaterials for bone regeneration 用于骨再生的可编程生物材料
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-09 DOI: 10.1016/j.mtbio.2024.101296
Peiran Song , Dongyang Zhou , Fuxiao Wang , Guangfeng Li , Long Bai , Jiacan Su
Programmable biomaterials are distinguished by their ability to adjust properties and functions on demand, in a periodic, reversible, or sequential manner. This contrasts with traditional biomaterials, which undergo irreversible, uncontrolled changes. This review synthesizes key advances in programmable biomaterials, examining their design principles, functionalities and applications in bone regeneration. It charts the transition from traditional to programmable biomaterials, emphasizing their enhanced precision, safety and control, which are critical from clinical and biosafety standpoints. We then classify programmable biomaterials into six types: dynamic nucleic acid-based biomaterials, electrically responsive biomaterials, bioactive scaffolds with programmable properties, nanomaterials for targeted bone regeneration, surface-engineered implants for sequential regeneration and stimuli-responsive release materials. Each category is analyzed for its structural properties and its impact on bone tissue engineering. Finally, the review further concludes by highlighting the challenges faced by programmable biomaterials and suggests integrating artificial intelligence and precision medicine to enhance their application in bone regeneration and other biomedical fields.
可编程生物材料的特点是能够以周期性、可逆或连续的方式按需调整特性和功能。这与传统生物材料形成鲜明对比,后者会发生不可逆、不可控的变化。这篇综述综述了可编程生物材料的主要进展,研究了它们的设计原理、功能和在骨再生中的应用。它描绘了从传统生物材料到可编程生物材料的转变过程,强调了可编程生物材料所具有的更高精度、安全性和可控性,这对于临床和生物安全至关重要。然后,我们将可编程生物材料分为六类:基于核酸的动态生物材料、电响应生物材料、具有可编程特性的生物活性支架、用于靶向骨再生的纳米材料、用于连续再生的表面工程植入物以及刺激响应释放材料。每一类材料都分析了其结构特性及其对骨组织工程的影响。最后,综述进一步总结了可编程生物材料所面临的挑战,并建议结合人工智能和精准医疗来提高其在骨再生和其他生物医学领域的应用。
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引用次数: 0
Capsule robots for the monitoring, diagnosis, and treatment of intestinal diseases 用于监测、诊断和治疗肠道疾病的胶囊机器人
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-09 DOI: 10.1016/j.mtbio.2024.101294
Xiangyu Wei , Peipei Xi , Minjie Chen , Ya Wen , Hao Wu , Li Wang , Yujuan Zhu , Yile Ren , Zhifeng Gu
Current evidence suggests that the intestine as the new frontier for human health directly impacts both our physical and mental health. Therefore, it is highly desirable to develop the intelligent tool for the enhanced diagnosis and treatment of intestinal diseases. During the past 20 years, capsule robots have opened new avenues for research and clinical applications, potentially revolutionizing human health monitor, disease diagnosis and treatment. In this review, we summarize the research progress of edible multifunctional capsule robots in intestinal diseases. To begin, we introduce the correlation between the intestinal microbiome, intestinal gas and human diseases. After that, we focus on the technical structure of edible multifunctional robots. Subsequently, the biomedical applications in the monitoring, diagnosis and treatment of intestinal diseases are discussed in detail. Last but not least, the main challenges of multifunctional capsule robots during the development process are summarized, followed by a vision for future development opportunities.
目前的证据表明,肠道作为人类健康的新领域,直接影响着我们的身心健康。因此,开发智能工具以加强对肠道疾病的诊断和治疗是非常可取的。在过去的 20 年中,胶囊机器人为研究和临床应用开辟了新的途径,有可能彻底改变人类的健康监测、疾病诊断和治疗。在这篇综述中,我们总结了可食用多功能胶囊机器人在肠道疾病方面的研究进展。首先,我们介绍了肠道微生物组、肠道气体与人类疾病之间的相关性。随后,我们重点介绍了可食用多功能机器人的技术结构。随后,详细讨论了肠道疾病监测、诊断和治疗方面的生物医学应用。最后,总结了多功能胶囊机器人在开发过程中面临的主要挑战,并展望了未来的发展机遇。
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引用次数: 0
Smart copper-doped clays in biomimetic microparticles for wound healing and infection control 用于伤口愈合和感染控制的生物仿生微粒中的智能掺铜粘土
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-09 DOI: 10.1016/j.mtbio.2024.101292
Marco Ruggeri , Cristian Nomicisio , Christine Taviot-Guého , Barbara Vigani , Cinzia Boselli , Pietro Grisoli , Antonia Icaro Cornaglia , Eleonora Bianchi , César Viseras , Silvia Rossi , Giuseppina Sandri
Chronic wounds are non-healing lesions characterized by a high degree of inflammation, posing significant challenges in clinical management due to the increased risk of severe infection. This study focuses on developing a powder for cutaneous application to enhance the healing and prevent infections in chronic wounds. The smart nanocomposites-based biomimetic microparticles here developed combine the properties of chitosan and of clays and represent a significant innovation in the field of biomaterials for skin regeneration since they possess enhanced antimicrobial properties, are multi-functional scaffolds and promote cell proliferation, support tissue reconstruction by mimicking the natural extracellular matrix, and provide hemostatic properties to control bleeding during wound closure. The microparticles were made of chitosan and doped with clay minerals, specifically montmorillonite or layered double hydroxides, containing copper ions. The synergistic combination of biomimetic polymers and clays aims to regulate cellular responses, angiogenesis, and extracellular matrix (ECM) deposition, leveraging the bioactive properties of both components to promote wound healing. Montmorillonite and layered double hydroxides were enriched with copper ions through intercalation or coprecipitation methods, respectively. The water-insoluble microparticles were prepared using a chitosan derivative, chitosan carbamate, synthesized to obtain chitosan-based microparticles via spray-drying without crosslinkers. Physico-chemical characterization confirmed the successful doping of Cu-clay interaction products in the microparticles. In addition to enhanced cell proliferation and hemostatic properties, the presence of Cu-clays boosted the microparticles’ antibacterial properties. Encouraging preclinical in vitro and in vivo results suggest that these smart nanocomposite biomimetic microparticles doped with Cu-enriched clay minerals could be promising candidates for simultaneously enhancing healing and controlling infections in chronic wounds.
慢性伤口是以高度炎症为特征的不愈合病变,由于严重感染的风险增加,给临床管理带来了巨大挑战。本研究的重点是开发一种用于皮肤应用的粉末,以促进慢性伤口的愈合并预防感染。本研究开发的基于智能纳米复合材料的仿生微颗粒结合了壳聚糖和粘土的特性,是皮肤再生生物材料领域的一项重大创新,因为它们具有更强的抗菌特性,是多功能支架,可促进细胞增殖,通过模拟天然细胞外基质支持组织重建,并具有止血特性,可在伤口闭合期间控制出血。微颗粒由壳聚糖制成,并掺杂了含铜离子的粘土矿物,特别是蒙脱石或层状双氢氧化物。仿生聚合物和粘土的协同组合旨在调节细胞反应、血管生成和细胞外基质(ECM)沉积,利用两种成分的生物活性特性促进伤口愈合。通过插层法或共沉淀法,蒙脱石和层状双氢氧化物分别富含铜离子。使用壳聚糖衍生物氨基甲酸壳聚糖制备了不溶于水的微颗粒,通过喷雾干燥法合成了壳聚糖基微颗粒,无需交联剂。物理化学表征证实,微颗粒中成功掺入了铜-粘土相互作用产物。除了增强细胞增殖和止血特性外,铜粘土的存在还提高了微颗粒的抗菌特性。令人鼓舞的临床前体外和体内研究结果表明,这些掺杂了富铜粘土矿物的智能纳米复合仿生微颗粒有望同时促进慢性伤口的愈合和控制感染。
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引用次数: 0
Recent research progresses of bioengineered biliary stents 生物工程胆道支架的最新研究进展
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-05 DOI: 10.1016/j.mtbio.2024.101290
Jianing Yan , Zhichao Ye , Xiaofeng Wang , Danyang Zhong , Ziyuan Wang , Tingting Yan , Tianyu Li , Yuyang Yuan , Yu Liu , Yifan Wang , Xiujun Cai
Bile duct lesion, including benign (eg. occlusion, cholelithiasis, dilatation, malformation) and malignant (cholangiocarcinoma) diseases, is a frequently encountered challenge in hepatobiliary diseases, which can be repaired by interventional or surgical procedures. A viable cure for bile duct lesions is implantation with biliary stents. Despite the placement achieved by current clinical biliary stents, the creation of functional and readily transplantable biliary stents remains a formidable obstacle. Excellent biocompatibility, stable mechanics, and absorbability are just a few benefits of using bioengineered biliary stents, which can also support and repair damaged bile ducts that drain bile. Additionally, cell sources & organoids derived from the biliary system that are loaded onto scaffolds can encourage bile duct regeneration. Therefore, the implantation of bioengineered biliary stent is considered as an ideal treatment for bile duct lesion, holding a broad potential for clinical applications in future. In this review, we look back on the development of conventional biliary stents, biodegradable biliary stents, and bioengineered biliary stents, highlighting the crucial elements of bioengineered biliary stents in promoting bile duct regeneration. After providing an overview of the various types of cell sources & organoids and fabrication methods utilized for the bioengineering process, we present the in vitro and in vivo applications of bioengineered biliary ducts, along with the latest advances in this exciting field. Finally, we also emphasize the ongoing challenges and future development of bioengineered biliary stents.
胆管病变,包括良性(如闭塞、胆石症、扩张、畸形)和恶性(胆管癌)疾病,是肝胆疾病中经常遇到的难题,可通过介入或外科手术进行修复。胆管病变的可行治疗方法是植入胆道支架。尽管目前临床上的胆道支架已经实现了置入,但制造功能性的、可移植的胆道支架仍然是一个巨大的障碍。生物工程胆道支架具有良好的生物相容性、稳定的力学性能和可吸收性,这些只是生物工程胆道支架的几个优点,它还能支撑和修复受损的胆管,排出胆汁。此外,将源自胆道系统的细胞来源和amp;有机体装载到支架上,可以促进胆管再生。因此,植入生物工程胆道支架被认为是治疗胆管病变的理想方法,在未来的临床应用中具有广阔的潜力。在这篇综述中,我们回顾了传统胆道支架、可降解胆道支架和生物工程胆道支架的发展历程,强调了生物工程胆道支架在促进胆管再生方面的关键因素。在概述了生物工程过程中使用的各种类型的细胞来源& 器官和制造方法后,我们介绍了生物工程胆管的体外和体内应用,以及这一激动人心的领域的最新进展。最后,我们还强调了生物工程胆道支架目前面临的挑战和未来的发展。
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引用次数: 0
One arrow two eagles: Multifunctional nano-system for macrophage reprogramming and osteoclastogenesis inhibition against inflammatory osteolysis 一箭双雕用于巨噬细胞重编程和抑制破骨细胞生成以对抗炎症性骨溶解的多功能纳米系统
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-10-05 DOI: 10.1016/j.mtbio.2024.101285
Tong Sha , Ze Wang , Jinwei Li , Yahong Wu , Jinbiao Qiang , Zhenming Yang , Yue Hu , Kaijuan Zheng , Shuyu Zhang , Haizhu Sun , Andrew K. Whittaker , Bai Yang , Hongchen Sun , Quan Lin , Ce Shi
Inflammatory osteolysis poses a significant worldwide threat to public health. However, current monotherapies, which target either the prevention of the inflammatory response or the attenuation of osteoclast (OC) formation, have limited efficacy due to the complexity of the bone immune system being overlooked. Herein, by means of modifying salmon calcitonin (sCT), a multifunctional nano-system (AuNDs-sCT) was designed to synergistically inhibit OC differentiation and reverse the inflammatory microenvironment against inflammatory osteolysis. On the one hand, AuNDs-sCT effectively restrained OC differentiation by binding to the calcitonin receptors on the surface of OC precursors, resulting in the down-regulation of OC-specific genes and proteins. The targeted capacity of AuNDs-sCT provided a more durable and precise therapeutic effect. On the other hand, AuNDs-sCT exhibited antioxidant and anti-inflammatory effects, which regulated the polarization “switch” from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype in macrophages by the inhibition of NF-κB p65 phosphorylation, thereby effectively reversed the local inflammatory microenvironment. Additionally, AuNDs-sCT served as a promising fluorescent probe, enabling real-time visualization of the therapeutic process. This capability is expected to optimize drug administration and evaluate therapeutic effects. In summary, by inhibiting OC differentiation and reprogramming macrophages, AuNDs-sCT successfully realized drug repurposing and achieved the “one arrow two eagles” therapeutic strategy, which offers a synergistic and effective treatment option for the clinical management of inflammatory osteolysis.
炎症性骨溶解对全球公众健康构成重大威胁。然而,由于忽视了骨免疫系统的复杂性,目前针对预防炎症反应或抑制破骨细胞(OC)形成的单一疗法疗效有限。本文通过对鲑鱼降钙素(sCT)进行修饰,设计出一种多功能纳米系统(AuNDs-sCT),可协同抑制破骨细胞分化,逆转炎症微环境,防止炎症性骨溶解。一方面,AuNDs-sCT通过与OC前体表面的降钙素受体结合,有效抑制OC分化,从而导致OC特异性基因和蛋白的下调。AuNDs-sCT 的靶向能力提供了更持久、更精确的治疗效果。另一方面,AuNDs-sCT 具有抗氧化和抗炎作用,通过抑制 NF-κB p65 磷酸化,调节巨噬细胞从促炎 M1 表型向抗炎 M2 表型的极化 "切换",从而有效逆转局部炎症微环境。此外,AuNDs-sCT 还可作为一种前景看好的荧光探针,实现治疗过程的实时可视化。这一功能有望优化给药和评估治疗效果。总之,AuNDs-sCT通过抑制OC分化和重编程巨噬细胞,成功实现了药物的再利用,实现了 "一箭双雕 "的治疗策略,为临床治疗炎性骨溶解提供了一种协同有效的治疗方案。
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Materials Today Bio
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