Biomaterials最新文献_第2页

Dynamic changes in the structure and function of brain mural cells around chronically implanted microelectrodes 长期植入微电极周围脑壁细胞结构和功能的动态变化。

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-11-12 DOI: 10.1016/j.biomaterials.2024.122963

Steven M. Wellman , Adam M. Forrest , Madeline M. Douglas , Ashwat Subbaraman , Guangfeng Zhang , Takashi D.Y. Kozai

Integration of neural interfaces with minimal tissue disruption in the brain is ideal to develop robust tools that can address essential neuroscience questions and combat neurological disorders. However, implantation of intracortical devices provokes severe tissue inflammation within the brain, which requires a high metabolic demand to support a complex series of cellular events mediating tissue degeneration and wound healing. Pericytes, peri-vascular cells involved in blood-brain barrier maintenance, vascular permeability, waste clearance, and angiogenesis, have recently been implicated as potential perpetuators of neurodegeneration in brain injury and disease. While the intimate relationship between pericytes and the cortical microvasculature have been explored in other disease states, their behavior following microelectrode implantation, which is responsible for direct blood vessel disruption and dysfunction, is currently unknown. Using two-photon microscopy we observed dynamic changes in the structure and function of pericytes during implantation of a microelectrode array over a 4-week implantation period. Pericytes respond to electrode insertion through transient increases in intracellular calcium and underlying constriction of capillary vessels. Within days following the initial insertion, we observed an influx of new, proliferating pericytes which contribute to new blood vessel formation. Additionally, we discovered a potentially novel population of reactive immune cells in close proximity to the electrode-tissue interface actively engaging in encapsulation of the microelectrode array. Finally, we determined that intracellular pericyte calcium can be modulated by intracortical microstimulation in an amplitude- and frequency-dependent manner. This study provides a new perspective on the complex biological sequelae occurring at the electrode-tissue interface and will foster new avenues of potential research consideration and lead to development of more advanced therapeutic interventions towards improving the biocompatibility of neural electrode technology.

将神经接口与对大脑组织破坏最小的设备整合在一起，是开发强大工具的理想选择，这些工具可以解决重要的神经科学问题，防治神经系统疾病。然而，皮质内装置的植入会引发脑内严重的组织炎症，需要大量新陈代谢来支持一系列介导组织变性和伤口愈合的复杂细胞事件。周细胞是参与血脑屏障维护、血管通透性、废物清除和血管生成的血管周围细胞，最近被认为是脑损伤和疾病中神经变性的潜在延续者。虽然在其他疾病状态下已对周细胞与大脑皮层微血管之间的密切关系进行了探讨，但目前还不清楚它们在微电极植入后的行为会直接导致血管破坏和功能障碍。我们使用双光子显微镜观察了微电极阵列植入 4 周后周细胞结构和功能的动态变化。周细胞通过细胞内钙的短暂增加和毛细血管的潜在收缩对电极的插入做出反应。在首次插入后的几天内，我们观察到大量新的、增殖的周细胞涌入，这有助于新血管的形成。此外，我们还在电极-组织界面附近发现了潜在的新型反应性免疫细胞群，它们正积极地参与微电极阵列的封装。最后，我们确定细胞周质内的钙可以通过皮层内微刺激以振幅和频率依赖的方式进行调节。这项研究为了解电极-组织界面发生的复杂生物后遗症提供了一个新的视角，并将为潜在的研究开辟新的途径，从而开发出更先进的治疗干预措施，改善神经电极技术的生物兼容性。

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引用次数: 0

Self-healing Ppy-hydrogel promotes diabetic skin wound healing through enhanced sterilization and macrophage orchestration triggered by NIR 自愈合PY-水凝胶通过近红外引发的增强杀菌和巨噬细胞协调作用促进糖尿病皮肤伤口愈合。

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-11-12 DOI: 10.1016/j.biomaterials.2024.122964

Zhuangzhuang Chu , Xingdan Liu , Tong Zhao , Dongya Jiang , Jing Zhao , Xiaohua Dong , Kelvin W.K. Yeung , Xuanyong Liu , Yun Liao , Liping Ouyang

Non-healing diabetic foot ulcers are the knotty public health issue due to the uncontrolled bacterial infection, prolonged inflammation, and inferior vessel remodeling. In this work, polypyrrole (Ppy) was added into the hybrid hydrogel containing polyvinyl alcohol (PVA), polyethylene glycol (PEG), and hyaluronan (HA) to acquire superior mechanism and photothermal ability. The Ppy composited hybrid hydrogel could effectively kill bacteria through accumulating heat on the hydrogel surface. RNA-Seq analysis shows that the heat accumulation could enhance phagosome of macrophage and M1 activation, which further accelerate bacteria clearance. Benefitting from the bacteria clearance, macrophage could transform its phenotype to M2 in Ppy composited hybrid hydrogel group with near infrared light (NIR) stimulation. The related genes expression in keratinization, keratinocyte differentiation, and establishment of the skin barrier in the skin were up-regulated and collagen and vascular endothelial growth factor (VEGF) expression level are also enhanced. In summary, Ppy composited hybrid hydrogel could effectively solve the issues of infection and poor wound healing in diabetic foot ulcers, making it an ideal candidate dressing for the treatment of chronic wounds.

糖尿病足溃疡不愈合是一个棘手的公共卫生问题，其原因是细菌感染未得到控制、炎症持续时间过长以及血管重塑不良。在这项研究中，聚吡咯（Ppy）被添加到含有聚乙烯醇（PVA）、聚乙二醇（PEG）和透明质酸（HA）的混合水凝胶中，以获得优异的机理和光热能力。Ppy 复合杂化水凝胶可通过在水凝胶表面积聚热量来有效杀灭细菌。RNA-Seq分析表明，蓄热可增强巨噬细胞的吞噬功能和M1活化，从而进一步加速细菌的清除。在近红外光（NIR）的刺激下，Ppy 复合杂化水凝胶组中的巨噬细胞可从细菌清除中获益，将其表型转变为 M2。皮肤角质化、角质细胞分化和皮肤屏障建立的相关基因表达上调，胶原蛋白和血管内皮生长因子（VEGF）的表达水平也有所提高。总之，Ppy 复合杂化水凝胶能有效解决糖尿病足溃疡感染和伤口愈合不良的问题，是治疗慢性伤口的理想候选敷料。

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引用次数: 0

Corrigendum to "Dual-step irradiation strategy to sequentially destroy singlet oxygen-responsive polymeric micelles and boost photodynamic cancer therapy" [Biomater. 275 (2021) 120959]. 双步辐照策略连续破坏单线态氧响应性聚合物胶束并促进光动力癌症疗法》[Biomater. 275 (2021) 120959]的更正。

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-11-12 DOI: 10.1016/j.biomaterials.2024.122952

Kai Deng, Hui Yu, Jia-Mi Li, Kun-Heng Li, Hong-Yang Zhao, Min Ke, Shi-Wen Huang

引用次数: 0

Biodegradable stimulating electrodes for resident neural stem cell activation in vivo 用于激活体内驻留神经干细胞的可生物降解刺激电极。

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-11-09 DOI: 10.1016/j.biomaterials.2024.122957

Tianhao Chen , Kylie Sin Ki Lau , Aryan Singh , Yi Xin Zhang , Sara Mohseni Taromsari , Meysam Salari , Hani E. Naguib , Cindi M. Morshead

Brain stimulation has been recognized as a clinically effective strategy for treating neurological disorders. Endogenous brain neural precursor cells (NPCs) have been shown to be electrosensitive cells that respond to electrical stimulation by expanding in number, undergoing directed cathodal migration, and differentiating into neural phenotypes in vivo, supporting the application of electrical stimulation to promote neural repair. In this study, we present the design of a flexible and biodegradable brain stimulation electrode for temporally regulated neuromodulation of NPCs. Leveraging the cathodally skewed electrochemical window of molybdenum and the volumetric charge transfer properties of conductive polymer, we engineered the electrodes with high charge injection capacity for the delivery of biphasic monopolar stimulation. We demonstrate that the electrodes are biocompatible and can deliver an electric field sufficient for NPC activation for 7 days post implantation before undergoing resorption in physiological conditions, thereby eliminating the need for surgical extraction. The biodegradable electrode demonstrated its potential to be used for NPC-based neural repair strategies.

脑刺激被认为是治疗神经系统疾病的一种临床有效策略。研究表明，内源性脑神经前体细胞（NPCs）是对电刺激敏感的细胞，它们对电刺激的反应是数量增加、定向阴极迁移以及在体内分化成神经表型，这为应用电刺激促进神经修复提供了支持。在这项研究中，我们设计了一种灵活、可生物降解的脑刺激电极，用于对 NPCs 进行时间调控的神经调节。利用钼的阴极偏斜电化学窗口和导电聚合物的体积电荷转移特性，我们设计了具有高电荷注入能力的电极，用于提供双相单极刺激。我们证明了电极的生物相容性，并能在植入后 7 天内提供足以激活鼻咽癌的电场，然后才会在生理条件下发生吸收，因此无需手术取出。这种可生物降解电极证明了其用于基于鼻咽癌的神经修复策略的潜力。

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引用次数: 0

Regulatory T cells engineered with polyphenol-functionalized immunosuppressant nanocomplexes for rebuilding periodontal hard tissue under inflammation-challenged microenvironment 利用多酚功能化免疫抑制剂纳米复合物设计的调节性 T 细胞，在炎症挑战的微环境下重建牙周硬组织。

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-11-09 DOI: 10.1016/j.biomaterials.2024.122961

Bo Zhang , Guidong Gong , Yunxiang He , Jialing Liu , Bo Wang , Yifei Li , Jie Fang , Zhihe Zhao , Junling Guo

Global aging heightens the risk of oral disorders, among which periodontitis is the major cause of tooth loss in the aging population. The regeneration of damaged periodontal hard tissue is highly challenging due to the existence of the refractory local inflammation. Owing to the potent anti-inflammatory capabilities, regulatory T cells hold great promise in immunotherapies for tissue regeneration. However, the transferred regulatory T cells can alter their phenotypes and functions in local inflammatory milieu, significantly impairing their therapeutic efficacy. Herein, we introduce a novel regulatory T cell-based nanobiohybrid system bearing polyphenol-functionalized rapamycin nanocomplexes. The sustained in situ release of immunosuppressant rapamycin from the cell-attached nanocomplexes maintains the anti-inflammatory phenotype of regulatory T cells in the inflammatory milieu. The synergistic actions of the anti-inflammatory cytokines secreted and the immunosuppressant released guide a pro-resolving polarization of macrophages and enhance osteogenic differentiation of bone marrow-derived stromal cells. The stabilized phenotype of the regulatory T cells dramatically promoted the resolution of periodontal inflammation and the repair of the hard tissue (alveolar bone) in vivo. Overall, these studies highlight a potent regulatory T cell-based nanobiohybrid therapy to treat periodontitis by modulating periodontal immune microenvironment.

全球老龄化加剧了口腔疾病的风险，其中牙周炎是老龄人口牙齿脱落的主要原因。由于存在难治性局部炎症，受损牙周硬组织的再生极具挑战性。由于调节性 T 细胞具有强大的抗炎能力，因此在组织再生的免疫疗法中大有可为。然而，转入的调节性 T 细胞在局部炎症环境中会改变其表型和功能，从而严重影响其疗效。在这里，我们介绍了一种基于调节性 T 细胞的新型纳米生物杂交系统，该系统含有多酚功能化雷帕霉素纳米复合物。免疫抑制剂雷帕霉素从细胞附着的纳米复合物中持续原位释放，从而维持了调节性 T 细胞在炎症环境中的抗炎表型。分泌的抗炎细胞因子和释放的免疫抑制剂协同作用，引导巨噬细胞向有利于溶解的极化方向发展，并增强骨髓基质细胞的成骨分化。表型稳定的调节性 T 细胞极大地促进了牙周炎症的缓解和体内硬组织（牙槽骨）的修复。总之，这些研究强调了通过调节牙周免疫微环境来治疗牙周炎的一种有效的基于调节性 T 细胞的纳米生物混合疗法。

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引用次数: 0

Sensorable zwitterionic antibacterial hydrogel for wound electrostimulation therapy 用于伤口电刺激疗法的可感应齐聚物抗菌水凝胶

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-11-09 DOI: 10.1016/j.biomaterials.2024.122958

Jinghua Li , Meijun Chen , Shaowen Cheng , Shegan Gao , Jingming Zhai , Dongmei Yu , Jianping Wang , Jianbo Zhang , Kaiyong Cai

Wound healing process has always been a focal point of concern, with a plethora of hydrogel dressings available; however, their therapeutic efficacy remains a hindrance to wound closure. This article reports on a dual-network conductive system, PEDOT:PSS-co-PSBMA/XLG (PPSX) hydrogel dressing, Constructed using poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT: PSS) in combination with zwitterionic N, N-dimethyl-N-(2-methacryloyloxyethyl)-N- (3-sulfopropyl) ammonium betaine (SBMA) and nanoclay-synthesized lithium magnesium silicate (XLG). The hydrogel powder produced from it can absorb interfacial water within 30 s via physical interactions to spontaneously form hydrogels of arbitrary shapes. With a conductivity of 1.8 s/m, it can be utilized for developing flexible sensing bioelectronic devices to monitor human activities (facial expressions, blinking, swallowing, speaking, joint movements), as well as constructing electrodes for monitoring muscle movements and motorial intensity. More importantly, PPSX hydrogel effectively inhibits bacterial growth and promotes cell proliferation, thus facilitating wound healing and presenting extensive application prospects in the medical field.

伤口愈合过程一直是人们关注的焦点，水凝胶敷料层出不穷；然而，其治疗效果仍然是伤口愈合的障碍。本文报告了一种双网络导电系统--PEDOT:PSS-co-PSBMA/XLG（PPSX）水凝胶敷料，该敷料由聚（3,4-亚乙二氧基噻吩）:聚（苯乙烯磺酸）（PEDOT：PSS）与滋阴离子 N，N-二甲基-N-（2-甲基丙烯酰氧乙基）-N-（3-磺丙基）甜菜碱铵（SBMA）和纳米粘土合成的硅酸镁锂（XLG）结合制成。由其制成的水凝胶粉末可在 30 秒内通过物理相互作用吸收界面水，自发形成任意形状的水凝胶。它的电导率为 1.8 s/m，可用于开发监测人体活动（面部表情、眨眼、吞咽、说话、关节运动）的柔性传感生物电子设备，以及构建监测肌肉运动和运动强度的电极。更重要的是，PPSX 水凝胶能有效抑制细菌生长，促进细胞增殖，从而促进伤口愈合，在医疗领域具有广泛的应用前景。

{"title":"Sensorable zwitterionic antibacterial hydrogel for wound electrostimulation therapy","authors":"Jinghua Li , Meijun Chen , Shaowen Cheng , Shegan Gao , Jingming Zhai , Dongmei Yu , Jianping Wang , Jianbo Zhang , Kaiyong Cai","doi":"10.1016/j.biomaterials.2024.122958","DOIUrl":"10.1016/j.biomaterials.2024.122958","url":null,"abstract":"<div><div>Wound healing process has always been a focal point of concern, with a plethora of hydrogel dressings available; however, their therapeutic efficacy remains a hindrance to wound closure. This article reports on a dual-network conductive system, PEDOT:PSS-co-PSBMA/XLG (PPSX) hydrogel dressing, Constructed using poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT: PSS) in combination with zwitterionic N, N-dimethyl-N-(2-methacryloyloxyethyl)-N- (3-sulfopropyl) ammonium betaine (SBMA) and nanoclay-synthesized lithium magnesium silicate (XLG). The hydrogel powder produced from it can absorb interfacial water within 30 s via physical interactions to spontaneously form hydrogels of arbitrary shapes. With a conductivity of 1.8 s/m, it can be utilized for developing flexible sensing bioelectronic devices to monitor human activities (facial expressions, blinking, swallowing, speaking, joint movements), as well as constructing electrodes for monitoring muscle movements and motorial intensity. More importantly, PPSX hydrogel effectively inhibits bacterial growth and promotes cell proliferation, thus facilitating wound healing and presenting extensive application prospects in the medical field.</div></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":"315 ","pages":"Article 122958"},"PeriodicalIF":12.8,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

On-demand reprogramming of immunosuppressive microenvironment in tumor tissue via multi-regulation of carcinogenic microRNAs and RNAs dependent photothermal-immunotherapy using engineered gold nanoparticles for malignant tumor treatment 利用工程金纳米粒子对致癌微RNA和RNA依赖性光热免疫疗法进行多调控，按需重编肿瘤组织中的免疫抑制微环境，用于恶性肿瘤治疗。

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-11-08 DOI: 10.1016/j.biomaterials.2024.122956

Li Chen , Wenjun Tang , Jie Liu , Man Zhu , Wenyun Mu , Xiaoyu Tang , Tao Liu , Zeren Zhu , Lin Weng , Yumeng Cheng , Yanmin Zhang , Xin Chen

The frequent immune escape of tumor cells and fluctuating therapeutic efficiency vary with each individual are two critical issues for immunotherapy against malignant tumor. Herein, we fabricated an intelligent core-shell nanoparticle (SNAs@CCM_R) to significantly inhibit the PD-1/PD-L1 mediated immune escape by on-demand regulation of various oncogenic microRNAs and perform RNAs dependent photothermal-immunotherapy to achieve precise and efficient treatment meeting the individual requirements of specific patients by in situ generation of customized tumor-associated antigens. The SNAs@CCM_R consisted of antisense oligonucleotides grafted gold nanoparticles (SNAs) as core and TLR7 agonist imiquimod (R837) functionalized cancer cell membrane (CCM) as shell, in which the acid-labile Schiff base bond was used to connect the R837 and CCM. During therapy, the acid environment of tumor tissue cleaved the Schiff base to generate free R837 and SNAs@CCM. The SNAs@CCM further entered tumor cells via CCM mediated internalization, and then specifically hybridized with over-expressed miR-130a and miR-21, resulting in effective inhibition of the migration and PD-L1 expression of tumor cells to avoid their immune escape. Meanwhile, the RNAs capture also caused significant aggregation of SNAs, which immediately generated photothermal agents within tumor cells to perform highly selective photothermal therapy under NIR irradiation. These chain processes not only damaged the primary tumor, but also produced plenty of tumor-associated antigens, which matured the surrounding dendritic cells (DCs) and activated anti-tumor T cells along with the released R837, resulting in the enhanced immunotherapy with suppressive immune escape. Both in vivo and in vitro experiments demonstrated that our nanoparticles were able to inhibit primary tumor and its metastasis via multi-regulation of carcinogenic microRNAs and RNAs dependent photothermal-immune activations, which provided a promising strategy to reprogram the immunosuppressive microenvironment in tumor tissue for better malignant tumor therapy.

肿瘤细胞的频繁免疫逃逸和因人而异的疗效波动是恶性肿瘤免疫治疗的两大关键问题。在此，我们制备了一种智能核壳纳米粒子（SNAs@CCMR），通过按需调控各种致癌微RNA，显著抑制PD-1/PD-L1介导的免疫逃逸，并通过原位生成定制的肿瘤相关抗原，进行RNAs依赖性光热免疫治疗，实现符合特定患者个体需求的精准高效治疗。SNAs@CCMR由反义寡核苷酸接枝金纳米粒子（SNAs）为核，TLR7激动剂咪喹莫特（R837）功能化癌细胞膜（CCM）为壳组成，其中R837与CCM之间采用酸性希夫碱连接。在治疗过程中，肿瘤组织的酸性环境会裂解希夫碱，生成游离的 R837 和 SNAs@CCM。SNAs@CCM 通过 CCM 介导的内化作用进一步进入肿瘤细胞，然后与过度表达的 miR-130a 和 miR-21 特异性杂交，从而有效抑制肿瘤细胞的迁移和 PD-L1 表达，避免其免疫逃逸。同时，RNAs 的捕获也会引起 SNAs 的显著聚集，SNAs 会立即在肿瘤细胞内产生光热剂，在近红外照射下进行高选择性光热治疗。这些连锁过程不仅破坏了原发肿瘤，还产生了大量肿瘤相关抗原，使周围的树突状细胞（DC）成熟，并与释放的 R837 一起激活了抗肿瘤 T 细胞，从而增强了抑制性免疫逃逸的免疫治疗效果。体内和体外实验均表明，我们的纳米颗粒能够通过多重调控致癌微RNA和RNA依赖的光热免疫激活抑制原发性肿瘤及其转移，这为重编程肿瘤组织中的免疫抑制微环境以更好地治疗恶性肿瘤提供了一种前景广阔的策略。

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引用次数: 0

Pulmonary delivery of dual-targeted nanoparticles improves tumor accumulation and cancer cell targeting by restricting macrophage interception in orthotopic lung tumors 双靶向纳米粒子的肺部给药通过限制巨噬细胞对正位肺肿瘤的拦截，改善了肿瘤积累和癌细胞靶向性。

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-11-08 DOI: 10.1016/j.biomaterials.2024.122955

Di Ge , Siqi Ma , Tingting Sun , Yunfei Li , Jiaxing Wei , Chenao Wang , Xiaoyuan Chen , Yonghong Liao

Despite the recognized potential of inhaled nanomedicines to enhance and sustain local drug concentrations for lung cancer treatment, the influence of macrophage uptake on targeted nanoparticle delivery to and within tumors remains unclear. Here, we developed three ligand-coated nanoparticles for pulmonary delivery in lung cancer therapy: phenylboronic acid-modified nanoparticles (PBA-NPs), PBA combined with folic acid (FA-PBA-NPs), and PBA with mannose (MAN-PBA-NPs). In vitro, MAN-PBA-NPs were preferentially internalized by macrophages, whereas FA-PBA-NPs exhibited superior uptake by cancer cells compared to macrophages. Following intratracheal instillation into mice with orthotopic Lewis lung carcinoma tumors, all three nanoparticles showed similar lung retention. However, MAN-PBA-NPs were more prone to interception by lung macrophages, which limited their accumulation in tumor tissues. In contrast, both PBA-NPs and FA-PBA-NPs achieved comparable high tumor accumulation (∼11.3% of the dose). Furthermore, FA-PBA-NPs were internalized by ∼30% of cancer cells, significantly more than the 10–18% seen with PBA-NPs or MAN-PBA-NPs. Additionally, FA-PBA-NPs loaded with icaritin effectively inhibited the Wnt/β-catenin pathway, resulting in superior anti-tumor efficacy through targeted cancer cell delivery. Overall, FA-PBA-NPs demonstrated advantageous competitive uptake kinetics by cancer cells compared to macrophages, enhancing tumor targeting and therapeutic outcomes.

尽管吸入纳米药物在提高和维持肺癌治疗的局部药物浓度方面具有公认的潜力，但巨噬细胞摄取对纳米粒子靶向输送到肿瘤和肿瘤内的影响仍不清楚。在此，我们开发了三种配体包裹的纳米颗粒，用于肺癌治疗的肺部给药：苯硼酸修饰纳米颗粒（PBA-NPs）、苯硼酸与叶酸结合的纳米颗粒（FA-PBA-NPs）和苯硼酸与甘露糖结合的纳米颗粒（MAN-PBA-NPs）。在体外，MAN-PBA-NPs 优先被巨噬细胞内化，而 FA-PBA-NPs 与巨噬细胞相比更容易被癌细胞吸收。在对小鼠进行气管内灌注后，这三种纳米粒子都显示出相似的肺部滞留性。但是，MAN-PBA-NPs 更容易被肺巨噬细胞截获，从而限制了其在肿瘤组织中的积累。相比之下，PBA-NPs和FA-PBA-NPs的肿瘤蓄积量相当高（占剂量的11.3%）。此外，FA-PBA-NPs 被 30% 的癌细胞内化，明显高于 PBA-NPs 或 MAN-PBA-NPs 的 10-18%。此外，装载了icaritin的FA-PBA-NPs还能有效抑制Wnt/β-catenin通路，从而通过靶向癌细胞递送产生卓越的抗肿瘤效果。总之，与巨噬细胞相比，FA-PBA-NPs 在癌细胞的竞争性吸收动力学方面更具优势，从而提高了肿瘤靶向性和治疗效果。

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引用次数: 0

Visible light-induced simultaneous bioactive amorphous calcium phosphate mineralization and in situ crosslinking of coacervate-based injectable underwater adhesive hydrogels for enhanced bone regeneration 可见光同时诱导具有生物活性的无定形磷酸钙矿化和基于共凝胶的可注射水下粘合水凝胶的原位交联，以促进骨再生。

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-11-07 DOI: 10.1016/j.biomaterials.2024.122948

Jinyoung Yun , Hyun Tack Woo , Sangmin Lee , Hyung Joon Cha

The field of bone tissue engineering is vital due to increasing bone disorders and limitations of traditional grafts. Injectable hydrogels offer minimally invasive solutions but often lack mechanical integrity and biological functionality, including osteoinductive capacity and structural stability under physiological conditions. To address these issues, we propose a coacervate-based injectable adhesive hydrogel that utilizes the dual functionality of in situ photocrosslinking and osteoinductive amorphous calcium phosphate formation, both of which are activated simultaneously by visible light irradiation. The developed hydrogel formulation integrated a photoreactive agent with calcium ions and phosphonodiol in a matrix of tyramine-conjugated alginate and RGD peptide-fused bioengineered mussel adhesive protein, promoting rapid setting, robust underwater adhesion, and bioactive mineral deposition. The hydrogel also exhibited superior mechanical properties, including enhanced underwater tissue adhesive strength and compressive resistance. In vivo evaluation using a rat femoral tunnel defect model confirmed the efficacy of the developed adhesive hydrogel in facilitating easy application to irregularly shaped defects through injection, rapid bone regeneration without the addition of bone grafts, and integration within the defect sites. This injectable adhesive hydrogel system holds significant potential for advancing bone tissue engineering, providing a versatile, efficient, and biologically favorable alternative to conventional bone repair methodologies.

骨组织工程领域非常重要，因为骨病日益增多，而传统移植物存在局限性。可注射水凝胶提供了微创解决方案，但往往缺乏机械完整性和生物功能，包括骨诱导能力和生理条件下的结构稳定性。为了解决这些问题，我们提出了一种基于共凝胶的可注射粘合剂水凝胶，它利用原位光交联和诱导骨形成无定形磷酸钙的双重功能，这两种功能在可见光照射下同时激活。所开发的水凝胶配方将光活性剂、钙离子和磷酰二醇整合在酪胺共轭海藻酸盐和融合了 RGD 肽的生物工程贻贝粘合蛋白基质中，促进了快速凝固、强大的水下粘附性和生物活性矿物质沉积。这种水凝胶还具有优异的机械性能，包括增强的水下组织粘附强度和抗压性。使用大鼠股骨隧道缺损模型进行的体内评估证实了所开发的粘合剂水凝胶在以下方面的功效：易于通过注射应用于不规则形状的缺损；无需添加骨移植物即可实现快速骨再生；以及与缺损部位融为一体。这种可注射的粘合剂水凝胶系统具有推动骨组织工程的巨大潜力，为传统的骨修复方法提供了一种多功能、高效和生物上有利的替代方法。

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引用次数: 0

Emerging COX-2 inhibitors-based nanotherapeutics for cancer diagnosis and treatment 用于癌症诊断和治疗的基于 COX-2 抑制剂的新兴纳米疗法。

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials

Pub Date : 2024-11-07 DOI: 10.1016/j.biomaterials.2024.122954

Ruiping Huang , Jiang Yu , Baoyue Zhang , Xin Li , Hongzhuo Liu , Yongjun Wang

Increasing evidence has showed that tumorigenesis is closely linked to inflammation, regulated by multiple signaling pathways. Among these, the cyclooxygenase-2/prostaglandin E₂ (COX-2/PGE₂) axis plays a crucial role in the progression of both inflammation and cancer. Inhibiting the activity of COX-2 can reduce PGE₂ secretion, thereby suppressing tumor growth. Therefore, COX-2 inhibitors are considered potential therapeutic agents for cancers. However, their clinical applications are greatly hindered by poor physicochemical properties and serious adverse effects. Fortunately, the advent of nanotechnology offers solutions to these limitations, enhancing drug delivery efficiency and mitigating adverse effects. Given the considerable progress in this area, it is timely to review emerging COX-2 inhibitors-based nanotherapeutics for cancer diagnosis and therapy. In this review, we first outline the various antineoplastic mechanisms of COX-2 inhibitors, then comprehensively summarize COX-2 inhibitors-based nanotherapeutics for cancer monotherapy, combination therapy, and diagnosis. Finally, we highlight and discuss future perspectives and challenges in the development of COX-2 inhibitors-based nanomedicine.

越来越多的证据表明，肿瘤的发生与炎症密切相关，并受多种信号通路的调控。其中，环氧化酶-2/前列腺素 E2（COX-2/PGE2）轴在炎症和癌症的发展过程中起着至关重要的作用。抑制 COX-2 的活性可以减少 PGE2 的分泌，从而抑制肿瘤的生长。因此，COX-2 抑制剂被认为是潜在的癌症治疗药物。然而，由于理化性质差和严重的不良反应，它们的临床应用受到很大阻碍。幸运的是，纳米技术的出现为这些限制提供了解决方案，提高了药物输送效率并减轻了不良反应。鉴于该领域取得的长足进步，现在正是回顾基于 COX-2 抑制剂的新兴纳米疗法在癌症诊断和治疗中的应用的好时机。在这篇综述中，我们首先概述了 COX-2 抑制剂的各种抗肿瘤机制，然后全面总结了基于 COX-2 抑制剂的纳米疗法在癌症单药治疗、联合治疗和诊断中的应用。最后，我们强调并讨论了基于 COX-2 抑制剂的纳米药物开发的未来前景和挑战。

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引用次数: 0