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A novel nanomedicine integrating ferroptosis and photothermal therapy, well-suitable for PD-L1-mediated immune checkpoint blockade 新型纳米药物融合了铁跃迁和光热疗法,非常适合 PD-L1 介导的免疫检查点阻断疗法
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-16 DOI: 10.1016/j.mtbio.2024.101346
Yujun Bao , Guanghao Li , Siqi Li , Haishui Zhou , Ziqing Yang , Zhiqiang Wang , Rui Yan , Changhong Guo , Yingxue Jin
Immunotherapy based on immune checkpoint blockade has emerged as a promising treatment strategy; however, the therapeutic efficacy is limited by the immunosuppressive microenvironment. Here, we developed a novel immune-activated nanoparticle (Fc-SS-Fe/Cu) to address the issue of insufficient immune infiltration. Specifically, the structure of Fc-SS-Fe/Cu collapsed in response to the tumor microenvironment, the ferrocene and disulfide bonds and the released Fe/Cu ions can effectively generate ·OH and deplete GSH to increase oxidative stress, thereby inducing ferroptosis. Withal, the positive feedback mechanisms of "laser-triggered mild-temperature photothermal therapy (PTT), PTT accelerated ferroptosis and LPO accumulation, LPO mediated HSPs down-regulated to promote PTT," effectively triggers immunogenic cell death (ICD) in tumor cells, significantly enhancing their immunogenicity. Moreover, the O2-generating ability induced by Fc-SS-Fe/Cu could reverse the hypoxic tumor microenvironment, and importantly, the expression of PD-L1 on tumor cell surfaces could be effectively downregulated by inhibiting the HIF-1α pathways, thereby augmenting the effect of anti-PD-L1 (αPD-L1) therapy. Therefore, this study provides valuable strategies into enhancing PD-L1-mediated ICB therapy.
基于免疫检查点阻断的免疫疗法已成为一种前景广阔的治疗策略;然而,其疗效受到免疫抑制微环境的限制。在这里,我们开发了一种新型免疫激活纳米粒子(Fc-SS-Fe/Cu)来解决免疫渗透不足的问题。具体来说,Fc-SS-Fe/Cu的结构会随着肿瘤微环境的变化而发生塌缩,二茂铁和二硫键以及释放的Fe/Cu离子能有效生成-OH并消耗GSH,从而增加氧化应激,进而诱导铁变态反应。最终,"激光触发的温和温度光热疗法(PTT)、PTT 加速铁跃迁和 LPO 积累、LPO 介导的 HSPs 下调促进 PTT "的正反馈机制有效地引发了肿瘤细胞的免疫原性细胞死亡(ICD),显著增强了肿瘤细胞的免疫原性。此外,Fc-SS-Fe/Cu诱导的O2生成能力可逆转缺氧的肿瘤微环境,重要的是,通过抑制HIF-1α通路,可有效下调肿瘤细胞表面PD-L1的表达,从而增强抗PD-L1(αPD-L1)治疗的效果。因此,本研究为加强 PD-L1 介导的 ICB 治疗提供了有价值的策略。
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引用次数: 0
Nickel–titanium alloy porous scaffolds based on a dominant cellular structure manufactured by laser powder bed fusion have satisfactory osteogenic efficacy 通过激光粉末床融合技术制造的基于优势细胞结构的镍钛合金多孔支架具有令人满意的成骨功效
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-15 DOI: 10.1016/j.mtbio.2024.101344
Jiaming Lin , An Yan , Anfei Huang , Qinglian Tang , Jinchang Lu , Huaiyuan Xu , Yufeng Huang , Tianqi Luo , Zhihao Chen , Anyu Zeng , Xiaojun Zhu , Chao Yang , Jin Wang
Nickel–titanium (NiTi) alloy is a widely utilized medical shape memory alloy (SMA) known for its excellent shape memory effect and superelasticity. Here, laser powder bed fusion (LPBF) technology was employed to fabricate a porous NiTi alloy scaffold featuring a topologically optimized dominant cellular structure that demonstrates favorable physical and superior biological properties. Utilizing a porous structure topology optimization method informed by the stress state of human bones, two types of cellular structures—compression and torsion—were designed, and porous scaffolds were produced via LPBF. The physical properties of the porous NiTi alloy scaffolds were evaluated to confirm their biocompatibility, while their osteogenic efficacy was investigated through both in vivo and in vitro experiments, with comparisons made against a traditional octahedral unit cell structure. NiTi alloy porous scaffolds can be nearly net-shaped via LPBF and exhibit favorable physical properties, including a low elastic modulus, high hydrophilicity, a specific linear expansion rate, as well as superelastic and shape memory effects. These scaffolds demonstrate excellent biocompatibility, support in vitro osteogenesis, and possess significant in vivo bone ingrowth capabilities. When compared to titanium alloys, NiTi alloys show comparable osteogenic properties in vitro but superior bone ingrowth properties in vivo. Additionally, among octahedral-type, torsion-type, and topologically optimized compression-type porous scaffolds, the latter demonstrates enhanced bone ingrowth properties. LPBF technology is effective for manufacturing porous NiTi alloy scaffolds with fine pore structures and excellent mechanical properties. The scaffolds based on topologically optimized dominant cellular structures facilitate satisfactory and efficient bone formation.
镍钛(NiTi)合金是一种广泛应用的医用形状记忆合金(SMA),以其出色的形状记忆效果和超弹性而著称。本文采用激光粉末床熔融(LPBF)技术制造了一种多孔镍钛合金支架,这种支架具有拓扑优化的主导细胞结构,具有良好的物理和生物特性。根据人体骨骼的应力状态,利用多孔结构拓扑优化方法,设计了两种细胞结构--压缩和扭转,并通过 LPBF 制备了多孔支架。对多孔镍钛合金支架的物理性质进行了评估,以确认其生物相容性,同时通过体内和体外实验研究了其成骨功效,并与传统的八面体单胞结构进行了比较。镍钛合金多孔支架可通过 LPBF 几乎呈网状,并表现出良好的物理特性,包括低弹性模量、高亲水性、特定线膨胀率以及超弹性和形状记忆效应。这些支架具有良好的生物相容性,支持体外成骨,并具有显著的体内骨生长能力。与钛合金相比,镍钛合金的体外成骨性能相当,但体内骨生长性能更优。此外,在八面体型、扭转型和拓扑优化压缩型多孔支架中,后者具有更强的骨生长特性。LPBF 技术可有效制造具有细孔结构和优异机械性能的多孔镍钛合金支架。基于拓扑优化的优势细胞结构的支架可促进令人满意的高效骨形成。
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引用次数: 0
Injectable microgels containing genetically engineered bacteria for colon cancer therapy through programmed Chemokine expression 含有基因工程细菌的可注射微凝胶,通过程序化趋化因子表达治疗结肠癌
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-13 DOI: 10.1016/j.mtbio.2024.101337
Yazhou Chen , Kehan Cai , Hui Zhao , Wenshuai Li , Xiaofang Gao , Yinzheng Fu , Kyubae Lee , SiTian Li , Shengjie Yao , Tao Chen
Chemokines are emerging as important targets for cancer immunotherapy due to their role in regulating immune cell migration and activation within the tumor microenvironment. Effective delivery and sustained presence of chemokines at the tumor site is essential for recruiting and activating immune cells to exert anti-tumor effects. In this study, we report a genetically engineered bacterial cell factory designed for the continuous production of chemokine CCL21 in a controlled manner. To decrease the formation of infusion bodies (IBs) in bacteria, we used thioredoxin (Trx) as the fusion partner and cloned at N-terminal of the target protein. The commonly used promoters, pT7-LacO, pBV220, and pDawn, were employed to explore the influence of various inducers on the expression of CCL21 in bacteria. The engineered bacteria were finally encapsulated within spherical gelatin methacryloyl (GelMA) microgels, which not only maintained bacterial viability but also prolonged their retention in the intestines of mice. As a result, the sustained presence and localized production of CCL21 led to effective suppression of tumor growth.
趋化因子在调节肿瘤微环境中的免疫细胞迁移和激活方面发挥着重要作用,因此正在成为癌症免疫疗法的重要靶点。趋化因子在肿瘤部位的有效传递和持续存在对于招募和激活免疫细胞以发挥抗肿瘤作用至关重要。在这项研究中,我们报告了一种基因工程细菌细胞工厂,其设计目的是以可控方式持续生产趋化因子 CCL21。为了减少细菌中输液体(IB)的形成,我们使用硫代毒素(Trx)作为融合伙伴,并克隆了目标蛋白的 N-末端。我们采用了常用的启动子 pT7-LacO、pBV220 和 pDawn,探讨了各种诱导剂对 CCL21 在细菌中表达的影响。最后,工程细菌被包裹在球形明胶甲基丙烯酰(GelMA)微凝胶中,这不仅保持了细菌的活力,还延长了它们在小鼠肠道中的存留时间。因此,CCL21 的持续存在和局部产生有效抑制了肿瘤的生长。
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引用次数: 0
A high-water retention, self-healing hydrogel thyroid model for surgical training 用于外科手术训练的高保水、自愈合水凝胶甲状腺模型
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-13 DOI: 10.1016/j.mtbio.2024.101334
Liang Ma , Zhihao Zhu , Shijie Yu , Sidney Moses Amadi , Fei Zhao , Jing Zhang , Zhifei Wang
The evaluation of thyroid lesions through Fine-Needle Aspiration Biopsy (FNAB) is a common procedure that requires advanced hand manipulation skills. Conventional training models for this procedure lack essential features such as tactile sensation and the ability to repeat punctures similar to those of real organs. To improve the quality of training, we have developed a hydrogel thyroid model that possesses features such as high-water retention and self-healing properties. This model consists of polyvinyl alcohol (PVA), polyacrylic acid (PAA), and trehalose that enhance water retention. By utilizing indirect printing technology, this hydrogel-based thyroid model closely resembles those of porcine thyroid tissue in terms of compression modulus and friction coefficient, exhibiting exceptional conformability, flexibility, and a water retention rate of 94.7 % at 6 h. It also displays a thrust force range of 0–0.98 N during simulated puncture, closely approximating real FNAB operations. This model shows evidence that it effectively simulates thyroid tissue and can be utilized for repetitive FNAB training to enhance the proficiency of medical personnel. Our study focuses on introducing new possibilities for developing advanced materials training models to be utilized in the medical field.
通过细针抽吸活检(FNAB)评估甲状腺病变是一种常见的手术,需要高级的手部操作技能。该手术的传统训练模型缺乏基本特征,如触觉和重复类似真实器官穿刺的能力。为了提高培训质量,我们开发了一种水凝胶甲状腺模型,它具有高保水和自愈合特性。该模型由聚乙烯醇(PVA)、聚丙烯酸(PAA)和可增强保水性的树胶糖组成。通过采用间接打印技术,这种基于水凝胶的甲状腺模型在压缩模量和摩擦系数方面与猪甲状腺组织非常相似,表现出卓越的保形性和柔韧性,6 小时后的保水率达到 94.7%,而且在模拟穿刺过程中显示出 0-0.98 N 的推力范围,非常接近真实的 FNAB 操作。有证据表明,该模型能有效模拟甲状腺组织,可用于重复性 FNAB 培训,以提高医务人员的熟练程度。我们的研究重点在于为医学领域开发先进的材料培训模型提供新的可能性。
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引用次数: 0
Multifunctional hydrogels loaded with tellurium nanozyme for spinal cord injury repair 用于脊髓损伤修复的负载碲纳米酶的多功能水凝胶
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-12 DOI: 10.1016/j.mtbio.2024.101339
Jian Meng , Jingjing Sun , Jiali Kang , Shilei Ren , Miaomiao Xu , Runzhi Li , Xuhui Zhao , Yitong Yuan , Lei Xin , Ruiping Zhang
Spinal cord injury (SCI) results in severe neurological deficits due to disrupted neural pathways. While the spinal cord possesses limited self-repair capabilities, recent advancements in hydrogel-based therapies have shown promise. Polyphenol-based hydrogels, known for their neuroprotective properties, offer a suitable microenvironment for neural regeneration. In this study, a novel poly(lipoic acid)/poly(dopamine) adhesive hydrogel was developed as a versatile platform for delivering therapeutic agents. This hydrogel was loaded with methylcobalamin, a neurotrophic factor, and tellurium nanoenzymes, potent antioxidants. The nanoenzymes effectively mitigated oxidative stress and inflammation, while methylcobalamin promoted nerve regeneration. The combined therapeutic effects of the nanoenzymatic hydrogel demonstrated significant efficacy in repairing spinal cord injuries, highlighting its potential as a promising strategy for treating this debilitating condition.
脊髓损伤(SCI)会导致神经通路中断,造成严重的神经功能缺损。虽然脊髓的自我修复能力有限,但基于水凝胶的疗法的最新进展已显示出前景。以多酚为基础的水凝胶因其神经保护特性而闻名,为神经再生提供了合适的微环境。本研究开发了一种新型聚(硫辛酸)/聚(多巴胺)粘合水凝胶,作为输送治疗药物的多功能平台。这种水凝胶含有神经营养因子甲基钴胺素和强效抗氧化剂碲纳米酶。纳米酶有效缓解了氧化应激和炎症,而甲基钴胺素则促进了神经再生。纳米酶水凝胶的综合治疗效果在修复脊髓损伤方面显示出显著疗效,突显了其作为治疗这种衰弱病症的一种有前途的策略的潜力。
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引用次数: 0
Bioactive hydrogel synergizes neuroprotection, macrophage polarization, and angiogenesis to improve repair of traumatic brain injury 生物活性水凝胶协同神经保护、巨噬细胞极化和血管生成,改善创伤性脑损伤的修复效果
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-12 DOI: 10.1016/j.mtbio.2024.101335
Yifan Hao , Longbao Feng , Huiling Liu , Liming Zhou , Xiang Yu , Xinyue He , Huan Cheng , Long Jin , Changyong Wang , Rui Guo
Traumatic brain injury (TBI) can lead to severe neurotrauma, leading to long-term cognitive decline and even death. Massive neuronal loss and excessive neuroinflammation are critical issues in the treatment of secondary TBI. To tackle these challenges, we developed a GelMA and CSMA hydrogel loaded with Erythropoietin (EPO) and Interleukin-4 (IL-4), named GC/I/E. By directly loading the hydrogel with EPO, rapid neuroprotection and angiogenesis were achieved. Meanwhile, by loading Mesoporous silica nanoparticles (MSNs) with IL-4 (MSN@IL-4), sustained inflammation modulation during inflammation was attained. In vitro experiments demonstrated that GC/I/E hydrogel were biocompatible and could provide neuroprotection for HT22 cells in H2O2 environment, regulate RAW264.7 polarization from M1 to M2 phenotype and promote HUVEC angiogenesis. In vivo experiments demonstrated that GC/I/E hydrogel reduced brain edema and Nissl body damage, inhibited inflammatory expression of G3-FFAP and neural scarring, improved microvascular and vascular function reconstruction, and facilitated neuronal and synaptogenesis, ultimately improving neurofunctional recovery in TBI. RNA sequencing results demonstrated that GC/I/E hydrogel treatment significantly correlated with the regulation of genes such as apoptosis, inflammation regulation, and neural regeneration. This bioactive hydrogel with neuroprotection, inflammation modulation and promotion of angiogenesis has great potential for TBI treatment.
创伤性脑损伤(TBI)可导致严重的神经创伤,导致长期认知能力下降甚至死亡。大量神经元丢失和过度神经炎症是治疗继发性 TBI 的关键问题。为了应对这些挑战,我们开发了一种负载红细胞生成素(EPO)和白细胞介素-4(IL-4)的 GelMA 和 CSMA 水凝胶,命名为 GC/I/E。通过在水凝胶中直接添加 EPO,可实现快速的神经保护和血管生成。同时,通过在介孔二氧化硅纳米颗粒(MSNs)中添加IL-4(MSN@IL-4),可在炎症期间实现持续的炎症调节。体外实验表明,GC/I/E 水凝胶具有良好的生物相容性,能在 H2O2 环境中为 HT22 细胞提供神经保护,调节 RAW264.7 从 M1 到 M2 表型的极化,并促进 HUVEC 血管生成。体内实验表明,GC/I/E 水凝胶能减轻脑水肿和 Nissl 体损伤,抑制 G3-FFAP 的炎症表达和神经瘢痕形成,改善微血管和血管功能重建,促进神经元和突触的生成,最终改善创伤性脑损伤的神经功能恢复。RNA 测序结果表明,GC/I/E 水凝胶处理与细胞凋亡、炎症调节和神经再生等基因的调控显著相关。这种具有神经保护、炎症调节和促进血管生成功能的生物活性水凝胶在治疗创伤性脑损伤方面具有巨大潜力。
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引用次数: 0
Construction of vascular grafts based on tissue-engineered scaffolds 基于组织工程支架构建血管移植物
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-10 DOI: 10.1016/j.mtbio.2024.101336
Zhongliang Lang , Tianao Chen , Shilu Zhu , Xizhi Wu , Yongqi Wu , Xiaoping Miao , Qiang Wang , Liping Zhao , Zhiqiang Zhu , Ronald X. Xu
Cardiovascular disease (CVD) ranks among the leading causes of morbidity and mortality globally, primarily due to arterial occlusive disease. Vascular bypass remains the cornerstone of treatment; however, many patients lack suitable autologous vessels (e.g., saphenous vein) for grafting. Tissue-engineered vascular grafts (TEVGs) provide a viable alternative capable of integrating, remodeling, and repairing host vessels, responding to mechanical and biochemical stimuli. Currently, preparation methods for TEVGs are mainly categorized into scaffold-free and scaffold-based approaches. Scaffold-free methods exhibit comparatively weaker mechanical properties and limited research progress, whereas scaffold-based approaches show more promising applications due to their superior mechanical properties and biocompatibility. This review examines current research progress in materials, fabrication processes, functionalized modifications, cell implantation, and animal and clinical experiments for scaffold-based preparation of TEVGs. By exploring current challenges and future perspectives in this field, we expect to provide new insights into TEVGs development and expedite their clinical applications.
心血管疾病(CVD)是全球发病率和死亡率的主要原因之一,主要由动脉闭塞性疾病引起。血管搭桥仍然是治疗的基础;然而,许多患者缺乏合适的自体血管(如大隐静脉)进行移植。组织工程血管移植物(TEVGs)提供了一种可行的替代方法,能够整合、重塑和修复宿主血管,并对机械和生化刺激做出反应。目前,TEVGs 的制备方法主要分为无支架和基于支架的方法。无支架方法的机械性能相对较弱,研究进展有限;而基于支架的方法因其优越的机械性能和生物相容性,应用前景更为广阔。本综述探讨了目前在基于支架制备 TEVGs 的材料、制造工艺、功能化修饰、细胞植入以及动物和临床实验等方面的研究进展。通过探讨该领域当前面临的挑战和未来前景,我们希望能为 TEVGs 的开发提供新的见解,并加快其临床应用。
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引用次数: 0
Orchestrated copper-loaded nanoreactor for simultaneous induction of cuproptosis and immunotherapeutic intervention in colorectal cancer 协调铜负载纳米反应器,用于同时诱导杯状突变和干预结直肠癌的免疫治疗
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-09 DOI: 10.1016/j.mtbio.2024.101326
Jiasheng Li , Shanshan Ma , Qiuhua Lin , Qin Wang , Wuning Zhong , Chunyin Wei , Junjie Liu , Jie Chen , Duo Wang , Weizhong Tang , Tao Luo
Ion interference, including intracellular copper (Cu) overload, disrupts cellular homeostasis, triggers mitochondrial dysfunction, and activates cell-specific death channels, highlighting its significant potential in cancer therapy. Nevertheless, the insufficient intracellular Cu ions transported by existing Cu ionophores, which are small molecules with short blood half-lives, inevitably hamper the effectiveness of cuproptosis. Herein, the ESCu@HM nanoreactor, self-assembled from the integration of H-MnO2 nanoparticles with the Cu ionophore elesclomol (ES) and Cu, was fabricated to facilitate cuproptosis and further induce relevant immune responses. Specifically, the systemic circulation and tumoral accumulation of Cu, causing irreversible cuproptosis, work in conjunction with Mn2+, resulting in the repolarization of tumor-associated macrophages (TAMs) and amplification of the activation of the cGAS-STING pathway by damaged DNA fragments in the nucleus and mitochondria. This further stimulates antitumor immunity and ultimately reprograms the tumor microenvironment (TME) to inhibit tumor growth. Overall, ESCu@HM as a nanoreactor for cuproptosis and immunotherapy, not only improves the dual antitumor mechanism of ES and provides potential optimization for its clinical application, but also paves the way for innovative strategies for cuproptosis-mediated colorectal cancer (CRC) treatment.
离子干扰,包括细胞内铜(Cu)超载,会破坏细胞的平衡,引发线粒体功能障碍,并激活细胞特异性死亡通道,凸显了其在癌症治疗中的巨大潜力。然而,现有的铜离子载体都是血液半衰期较短的小分子,它们在细胞内转运的铜离子不足,不可避免地影响了铜中毒的效果。在此,我们制作了ESCu@HM纳米反应器,该反应器由H-MnO2纳米颗粒与铜离子载体伊利司莫尔(ES)和铜结合自组装而成,可促进杯突效应并进一步诱导相关免疫反应。具体来说,全身循环和肿瘤积聚的 Cu 会引起不可逆的杯突症,与 Mn2+ 共同作用,导致肿瘤相关巨噬细胞(TAMs)的再极化,并放大细胞核和线粒体中受损 DNA 片段对 cGAS-STING 通路的激活。这进一步刺激了抗肿瘤免疫,并最终重编程肿瘤微环境(TME),抑制肿瘤生长。总之,ESCu@HM 作为杯突酶和免疫疗法的纳米反应器,不仅改善了 ES 的双重抗肿瘤机制,为其临床应用提供了潜在的优化方案,而且为杯突酶介导的结直肠癌(CRC)治疗的创新策略铺平了道路。
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引用次数: 0
Self-healing hydrogels loaded with Spatholobi Caulis alleviate disc degeneration by promoting autophagy in nucelus pulposus 自愈合水凝胶载入 Spatholobi Caulis,通过促进髓核自噬缓解椎间盘退变
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-08 DOI: 10.1016/j.mtbio.2024.101323
Shenghao Cai , Rui Ding , Hongjun Zhang , Qirui Chen , Fen Yu , Yong Xia , Qi Chen , Xinxin Miao , Bin Zhou , Jiahui Chen , Le Liao , Xigao Cheng , Xiaoling Fu
Intervertebral disc degeneration (IDD) is a common degenerative disease of the spine that has a significant impact on both society and human health. Many studies have confirmed that there is a close relationship between IDD and senescence and apoptosis, and autophagy can combat apoptosis and senescence. Spatholobi caulis (SC) is an herb that contains various active compounds that are effective in tissue repair and regeneration, but it has not been explored in field of IDD. In this study, it was first found that SC can boost autophagy and reduce the apoptosis and senescence of Nucleus pulposus cell (NPCs). However, our animal studies revealed limited absorption of SC. To improve the bioavailability and efficacy of SC, we developed a hydrogel incorporating quaternary ammonium chitosan (QCS) and oxidized starch (OST) as carriers for SC. The QCS-OST/SC hydrogel exhibits excellent compatibility with cells, can be easily injected, and can release SC durably. At the cellular level, the QCS-OST/SC hydrogel enhances cell viability, initiates autophagy and release of the extracellular matrix (ECM), and inhibits cellular senescence and apoptosis. The injection of the QCS-OST/SC hydrogel via microneedles (MNs) into discs had successfully diminished disc degeneration in rats, which shows that this hydrogel has broad potential in the treatment of IDD.
椎间盘退变(IDD)是一种常见的脊柱退行性疾病,对社会和人类健康都有重大影响。许多研究证实,IDD 与衰老和细胞凋亡有密切关系,而自噬可以对抗细胞凋亡和衰老。Spatholobi caulis(SC)是一种草药,含有多种活性化合物,对组织修复和再生有效,但尚未在 IDD 领域进行探索。在这项研究中,我们首次发现 Spatholobi caulis 能促进自噬,减少核浆细胞(NPCs)的凋亡和衰老。然而,我们的动物实验发现 SC 的吸收有限。为了提高SC的生物利用度和疗效,我们开发了一种水凝胶,将季铵盐壳聚糖(QCS)和氧化淀粉(OST)作为SC的载体。QCS-OST/SC 水凝胶与细胞的相容性极佳,易于注射,并能持久释放 SC。在细胞水平上,QCS-OST/SC 水凝胶可提高细胞活力,促进自噬和细胞外基质(ECM)的释放,并抑制细胞衰老和凋亡。通过微针(MNs)将 QCS-OST/SC 水凝胶注入椎间盘,成功地减轻了大鼠的椎间盘退化,这表明这种水凝胶在治疗椎间盘突出症方面具有广泛的潜力。
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引用次数: 0
Cell-derived biomimetic drug delivery system for inflammatory bowel disease therapy 用于炎症性肠病治疗的细胞衍生生物仿生给药系统
IF 8.7 1区 医学 Q1 ENGINEERING, BIOMEDICAL Pub Date : 2024-11-08 DOI: 10.1016/j.mtbio.2024.101332
Wenjing Yang , Peihong Lin , Rui Gao , Zhengyu Fang , Zhouru Wang , Zhen Ma , Jing Shi , Wenying Yu
Inflammatory bowel disease (IBD) is a chronic recurrent disease with an increasing incidence year by year. At present, no safe and effective treatment for IBD exists. Thus, there is an urgent need to create new therapeutic options that have decreased adverse effects and positive clinical efficacy. A range of nanomaterials have fueled the advancement of nanomedicine in recent years, which is establishing more appealing and prospective treatment approaches for IBD. However, traditional synthetic nanomaterials still have some problems in the IBD drug delivery process, such as weak targeting ability of vectors, difficulty escaping immune surveillance, and poor biosecurity. Natural sources of biological nanomaterials have been identified to solve the above problems. A drug delivery system based on bionic technology is expected to achieve a new breakthrough in the targeted therapy of IBD by nanotechnology due to its organic integration of low immunogenicity and natural targeting of biological materials and the controllability and versatility of synthetic nanocarrier design. We begin this review by outlining the fundamental traits of both inflammatory and healthy intestinal microenvironments. Subsequently, we review the latest application of a cell-derived bionic drug delivery system in IBD therapy. Finally, we discuss the development prospects of this delivery system and challenges to its clinical translation. Biomimetic nanotherapy is believed to offer a new strategy for the treatment of IBD.
炎症性肠病(IBD)是一种慢性复发性疾病,发病率逐年上升。目前,尚无安全有效的 IBD 治疗方法。因此,迫切需要创造出不良反应小、临床疗效好的新疗法。近年来,一系列纳米材料推动了纳米医学的发展,为 IBD 的治疗提供了更具吸引力和前景的方法。然而,传统合成纳米材料在 IBD 给药过程中仍存在一些问题,如载体靶向能力弱、难以逃脱免疫监视、生物安全性差等。为解决上述问题,人们找到了生物纳米材料的天然来源。基于仿生技术的给药系统将生物材料的低免疫原性和天然靶向性与人工合成纳米载体设计的可控性和多功能性有机结合,有望在纳米技术靶向治疗 IBD 方面实现新的突破。本综述首先概述了炎症和健康肠道微环境的基本特征。随后,我们回顾了细胞衍生仿生给药系统在 IBD 治疗中的最新应用。最后,我们讨论了这种给药系统的发展前景及其临床转化所面临的挑战。仿生纳米疗法被认为是治疗 IBD 的新策略。
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引用次数: 0
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Materials Today Bio
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