Materials Science & Engineering C-Materials for Biological Applications最新文献_第10页

Thermomagneto-responsive injectable hydrogel for chondrogenic differentiation of mesenchymal stem cells 用于间充质干细胞软骨分化的热磁响应注射水凝胶

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-13 DOI: 10.1016/j.bioadv.2024.214115

Parvin Najafi , Elnaz Tamjid , Parviz Abdolmaleki , Mehrdad Behmanesh

Damaged cartilage tissue has a limited ability to self-heal due to its avascular nature and low cellularity. To effectively engineer cartilage tissue, innovative techniques such as injectable and interactive hydrogels using a minimally invasive approach are required to mimic the natural properties of cartilage. In this study, an injectable hydrogel containing magnetic iron oxide nanoparticles (MNPs) has been rationally designed to induce chondrogenic differentiation in bone marrow mesenchymal stem cells (BMSCs) using an external magnetic field application. The effect of the incorporation of MNPs with the surface functional group of either carboxyl or amine on the properties of the hydrogels (denoted as HS and HA samples, respectively) has been investigated, and compared to control hydrogel without MNPs (denoted as H). The hydrogels demonstrated thermomagnetic-responsive and shear-thinning behavior. Incorporating MNPs in the hydrogel combination resulted in the formation of a more robust network with increased compressive modulus (by 2 and 2.5 times), cell viability (by 24 % and 7 %), swelling ratio (by 97 % and 42 %) for HS and HA, respectively, as well as better cell adhesion. Also, incorporating MNPs resulted in decreased elastic modulus (by 28 and 5 times), biodegradation rate (by 5 % and 9 %), and viscosity (by 4 and 20 times) for HS and HA, respectively. The results of glycosaminoglycans (GAG) staining indicated the synergistic effect of MNP incorporation and magnetic field application in improving chondrogenic differentiation of BMSCs in vitro. The research findings could lead to the development of superior injectable hydrogels and bioinks for tissue engineering applications.

由于软骨组织无血管且细胞数量少，受损软骨组织的自我修复能力有限。为了有效地改造软骨组织，需要采用创新技术，如采用微创方法的可注射和交互式水凝胶，以模拟软骨的天然特性。本研究合理设计了一种含有磁性氧化铁纳米颗粒（MNPs）的可注射水凝胶，利用外部磁场诱导骨髓间充质干细胞（BMSCs）进行软骨分化。研究了加入表面官能团为羧基或胺的 MNPs 对水凝胶（分别称为 HS 样品和 HA 样品）性质的影响，并与不含 MNPs 的对照水凝胶（称为 H 样品）进行了比较。这些水凝胶具有热磁响应和剪切稀化行为。在水凝胶组合中加入 MNPs 可形成更坚固的网络，使 HS 和 HA 的压缩模量（分别增加 2 倍和 2.5 倍）、细胞存活率（分别增加 24% 和 7%）、溶胀率（分别增加 97% 和 42%）以及细胞粘附性更好。此外，加入 MNPs 后，HS 和 HA 的弹性模量（分别降低 28 倍和 5 倍）、生物降解率（分别降低 5% 和 9%）和粘度（分别降低 4 倍和 20 倍）均有所降低。糖胺聚糖（GAG）染色结果表明，MNP 的加入和磁场的应用在体外改善 BMSCs 软骨分化方面具有协同效应。这些研究成果将有助于开发用于组织工程应用的优质可注射水凝胶和生物墨水。

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引用次数: 0

Piezoelectric nanocomposite electrospun dressings: Tailoring mechanics for scar-free wound recovery 压电纳米复合电纺敷料：无疤痕伤口恢复的定制力学

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-13 DOI: 10.1016/j.bioadv.2024.214119

Chao Zhang , Wei Song , Xu Guo , Zhao Li , Yi Kong , Jinpeng Du , Linhao Hou , Yu Feng , Yuzhen Wang , Mengde Zhang , Liting Liang , Yuyan Huang , Jianjun Li , Dongzhen Zhu , Qinghua Liu , Yaxin Tan , Ziteng Zhao , Yantao Zhao , Xiaobing Fu , Sha Huang

Rational wound management and enhancing healing quality are critical in clinical practice. Electrical stimulation therapy (EST) has emerged as a valuable adjunctive treatment due to its safety and cost-effectiveness. Integrating piezoelectric materials into dressings offers a way to miniaturize and personalize electrotherapy, enhancing convenience. To address the impact of physical factors of dressings on wound healing, a nanocomposite piezoelectric electrospun dressing using poly(_L-lactic acid) (PLLA) and barium titanate (BaTiO₃) was developed. We intentionally exaggerated design flaws to mimic the characteristics of scar extracellular matrix (ECM), including the oriented thick fibers and high Young's modulus. Initially, these dressings promoted fibrosis and hindered functional regeneration. However, when the piezoelectric effect was triggered by ultrasound, the fibrotic phenotype was reversed, leading to scar-free healing with well-regenerated functional structures. This study highlights the significant therapeutic potential of piezoelectric dressings in skin wound treatment and underscores the importance of carefully designing the static physical properties of dressings for optimal efficacy.

在临床实践中，合理的伤口管理和提高愈合质量至关重要。电刺激疗法（EST）以其安全性和成本效益成为一种重要的辅助治疗方法。将压电材料集成到敷料中可实现电疗的微型化和个性化，从而提高治疗的便利性。为了解决敷料的物理因素对伤口愈合的影响，我们开发了一种使用聚乳酸（PLLA）和钛酸钡（BaTiO3）的纳米复合压电电纺敷料。我们有意夸大了设计缺陷，以模仿疤痕细胞外基质（ECM）的特征，包括取向粗纤维和高杨氏模量。起初，这些敷料会促进纤维化，阻碍功能再生。然而，当超声波触发压电效应时，纤维化表型被逆转，导致无疤痕愈合和功能结构的良好再生。这项研究凸显了压电敷料在皮肤伤口治疗中的巨大治疗潜力，并强调了精心设计敷料的静态物理特性以获得最佳疗效的重要性。

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引用次数: 0

Tailoring metabolic activity assays for tumour-engineered 3D models 为肿瘤工程三维模型量身定制新陈代谢活性检测方法。

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-12 DOI: 10.1016/j.bioadv.2024.214116

Julien Clegg , Rodrigo Curvello , Anastasiia Gabrielyan , Daniel Croagh , Sandra Hauser , Daniela Loessner

Monitoring cell behaviour in hydrogel-based 3D models is critical for assessing their growth and response to cytotoxic treatment. Resazurin-based PrestoBlue and AlamarBlue reagents are frequently used metabolic activity assays when determining cell responses. However, both assays are largely applied to cell monolayer cultures but yet to have a defined protocol for use in hydrogel-based 3D models. The assays' performance depends on the cell type, culture condition and measurement sensitivity. To better understand how both assays perform, we grew pancreatic cancer cells in gelatin methacryloyl and collagen hydrogels and evaluated their metabolic activity using different concentrations and incubation times of the PrestoBlue and AlamarBlue reagents. We tested reagent concentrations of 4 % and 10 % and incubation times of 45 min, 2 h and 4 h. In addition, we co-cultured cancer cells together with cancer-associated fibroblasts and peripheral blood mononuclear cells in gelatin methacryloyl hydrogels and subjected them to gemcitabine and nab-paclitaxel to evaluate how both assays perform when characterising cell responses upon drug treatment. CyQuant assays were conducted on the same samples and compared to data from the metabolic activity assays. In cancer monocultures, higher reagent concentration and incubation time increased fluorescent intensity. We found a reagent concentration of 10 % and an incubation time of 2 h suitable for all cell lines and both hydrogels. In multicellular 3D cultures, PrestoBlue and AlamarBlue assays detected similar cell responses upon drug treatment but overestimated cell growth. We recommend to assess cell viability and growth in conjunction with CyQuant assays that directly measure cell functions.

监测水凝胶三维模型中的细胞行为对于评估细胞的生长和对细胞毒性治疗的反应至关重要。在确定细胞反应时，基于石蕊青的 PrestoBlue 和 AlamarBlue 试剂是常用的代谢活性检测方法。不过，这两种检测方法主要应用于细胞单层培养，但在基于水凝胶的三维模型中使用时还没有明确的方案。这两种检测方法的性能取决于细胞类型、培养条件和测量灵敏度。为了更好地了解这两种检测方法的性能，我们在明胶甲基丙烯酰和胶原水凝胶中培养了胰腺癌细胞，并使用不同浓度和孵育时间的 PrestoBlue 和 AlamarBlue 试剂评估了它们的代谢活性。此外，我们还在明胶甲基丙烯酰水凝胶中将癌细胞与癌症相关成纤维细胞和外周血单核细胞共同培养，并让它们接受吉西他滨和纳布紫杉醇的治疗，以评估这两种检测方法在描述药物治疗时细胞反应的性能。对相同的样品进行了 CyQuant 检测，并与代谢活性检测的数据进行了比较。在癌症单一培养物中，试剂浓度和培养时间越高，荧光强度越高。我们发现，10% 的试剂浓度和 2 小时的孵育时间适用于所有细胞系和两种水凝胶。在多细胞三维培养中，PrestoBlue 和 AlamarBlue 检测法检测到的细胞对药物处理的反应相似，但高估了细胞的生长。我们建议结合直接测量细胞功能的 CyQuant 检测法来评估细胞活力和生长。

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引用次数: 0

Targeted delivery of Saikosaponin A and doxorubicin via hyaluronic acid-modified ZIF-8 nanoparticles for TNBC treatment: Inhibiting metastasis and reducing cardiotoxicity 通过透明质酸修饰的 ZIF-8 纳米粒子靶向输送赛可皂素 A 和多柔比星，用于 TNBC 治疗：抑制转移并降低心脏毒性

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-12 DOI: 10.1016/j.bioadv.2024.214114

Dandan Li , Yu Yao , Kun Wang , Chunyu Lei , Xianfeng Peng , Chengjian Cao , Ke Zhu , Ziyang Zhu , Fuqiang Shao

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen receptors, progesterone receptors, and HER2 expression, making traditional hormone and targeted therapies ineffective. Chemotherapy remains the primary treatment for TNBC; however, it has failed to adequately address the high rates of recurrence and metastasis, underscoring the urgent need for new therapeutic strategies. This study investigates Saikosaponin A (SSA), a compound extracted from traditional Chinese medicine, for its potential to enhance the efficacy of doxorubicin (DOX) chemotherapy while reducing TNBC metastasis and mitigating DOX-induced cardiotoxicity.

We first confirmed SSA's cardioprotective effects against DOX-induced cardiotoxicity, highlighting its potential as an adjunctive therapy for TNBC chemotherapy. Subsequently, through network pharmacology analysis, we identified that SSA may inhibit TNBC progression and metastasis by downregulating integrin β3, a key regulatory factor in tumor development. This was further validated through both in vivo and in vitro experiments. To address the poor bioavailability of SSA, we developed a novel drug delivery system utilizing hyaluronic acid (HA)-modified zeolitic imidazolate framework-8 (ZIF-8) nanoparticles for the co-delivery of SSA and DOX. This nano-drug system exhibited excellent stability and high drug-loading capacity, with loading efficiencies of 40.07 % for SSA and 43.07 % for DOX. After 24 h of nano-drug administration, the DOX concentration in the group using the nano-delivery system was 5.01 times higher than control group, demonstrated enhanced tumor-targeting capability. Furthermore, after 14 days of treatment, the tumor volume was reduced by 80.8 % compared to the control group, indicating significantly improved therapeutic efficacy (all P < 0.05).

This study systematically evaluates the potential of this dual drug-loaded nanocarrier in improving TNBC treatment, reducing DOX-induced cardiotoxicity, and inhibiting metastasis, offering a novel therapeutic approach that integrates traditional medicine with advanced nanotechnology.

三阴性乳腺癌（TNBC）是乳腺癌的一种侵袭性亚型，其特点是没有雌激素受体、孕激素受体和 HER2 表达，因此传统的激素和靶向治疗无效。化疗仍是 TNBC 的主要治疗方法，但它未能充分解决复发率和转移率高的问题，这凸显了对新治疗策略的迫切需求。本研究调查了一种从传统中药中提取的化合物--赛可皂甙 A（SSA），研究其在增强多柔比星（DOX）化疗疗效的同时减少 TNBC 转移和减轻 DOX 引起的心脏毒性的潜力。我们首先证实了 SSA 对 DOX 引起的心脏毒性具有保护作用，从而凸显了其作为 TNBC 化疗辅助疗法的潜力。随后，通过网络药理学分析，我们发现 SSA 可通过下调整合素 β3（肿瘤发生发展的关键调控因子）抑制 TNBC 的进展和转移。体内和体外实验进一步验证了这一点。为了解决 SSA 生物利用率低的问题，我们开发了一种新型给药系统，利用透明质酸（HA）修饰的沸石咪唑框架-8（ZIF-8）纳米颗粒共同给药 SSA 和 DOX。该纳米药物系统具有出色的稳定性和高载药能力，SSA和DOX的载药效率分别为40.07%和43.07%。给药 24 小时后，使用纳米给药系统组的 DOX 浓度是对照组的 5.01 倍，显示出更强的肿瘤靶向能力。此外，治疗 14 天后，肿瘤体积比对照组减少了 80.8%，表明疗效显著提高（所有 P

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引用次数: 0

The biological effects of copper alloying in Zn-based biodegradable arterial implants 锌基生物可降解动脉植入物中铜合金的生物效应。

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-08 DOI: 10.1016/j.bioadv.2024.214112

Lea Morath , Shebeer A. Rahim , Cole Baker , Deirdre E.J. Anderson , Monica T. Hinds , Malgorzata Sikora-Jasinska , Lindy Oujiri , Lisa Leyssens , Greet Kerckhofs , Grzegorz Pyka , Alexander A. Oliver , Jaroslaw W. Drelich , Jeremy Goldman

Biodegradable metals based on zinc are being developed to serve as temporary arterial scaffolding. Although the inclusion of copper is becoming more prevalent for grain refinement in zinc alloys, the biological activity of the copper component has not been well investigated. Here, two ZnCu alloys (0.8 and 1.5 wt% Cu) with and without thermal treatment were investigated for their hemocompatibility and biocompatibility. The microstructure was examined using scanning electron microscopy and X-ray diffraction. Zn-1.5Cu was found to contain nearly double the amount of second phase (CuZn₅) precipitates as compared to Zn-0.8Cu. Thermal treatment dissolved a portion of the precipitates into the matrix. Since copper is a well-known catalyst for NO generation, the metals were tested both for their ability to generate NO release and for their thrombogenicity. Cellular responses and in vivo corrosion were characterized by a 6 months in vivo implantation of metal wires into rat arteries. The as-received Zn-1.5Cu displayed the least neointimal growth and smooth muscle cell presence, although inflammation was slightly increased. Thermal treatment was found to worsen the biological response, as determined by an increased neointimal size, increased smooth muscle cell presence and small regions of necrotic tissue. There were no trends in NO release between the alloys and thermal treatments. Corrosion progressed predominately through a pitting mechanism in vivo, which was more pronounced for the thermally treated alloys, with a more uniform corrosion seen for as-received Zn-1.5Cu. Differences in biological response are speculated to be due to changes in microstructure and pitting corrosion behavior.

目前正在开发以锌为基础的可生物降解金属，以用作临时动脉支架。虽然在锌合金中加入铜以细化晶粒的做法越来越普遍，但铜成分的生物活性还没有得到很好的研究。在此，我们研究了两种经热处理和未经热处理的锌铜合金（铜含量分别为 0.8 和 1.5 wt%）的血液相容性和生物相容性。使用扫描电子显微镜和 X 射线衍射检查了合金的微观结构。与 Zn-0.8Cu 相比，Zn-1.5Cu 中第二相（CuZn5）沉淀物的含量几乎增加了一倍。热处理将部分沉淀物溶解到基体中。由于铜是众所周知的氮氧化物生成催化剂，因此对这些金属进行了氮氧化物释放能力和血栓形成能力测试。将金属丝植入大鼠动脉 6 个月后，对细胞反应和体内腐蚀进行了鉴定。尽管炎症反应略有增加，但在接受 Zn-1.5Cu 的情况下，新内膜生长和平滑肌细胞的存在最少。热处理会使生物反应恶化，表现为新内膜尺寸增大、平滑肌细胞增多以及坏死组织区域变小。合金和热处理之间的氮氧化物释放量没有变化趋势。体内腐蚀主要是通过点蚀机制进行的，热处理合金的腐蚀更为明显，而原样接收的 Zn-1.5Cu 的腐蚀更为均匀。据推测，生物反应的差异是由于微观结构和点蚀行为的变化造成的。

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引用次数: 0

An in vitro bioinspired approach to enhance the bioactivity of titanium implants via electrophoretic deposition and biomimetic mineralization of type i collagen 通过 i 型胶原蛋白的电泳沉积和仿生矿化提高钛植入物生物活性的体外生物启发方法。

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-08 DOI: 10.1016/j.bioadv.2024.214110

Man Wang , Muqi Jiang , Qi Wang , Yasheng Sun , Zhixiang Nie , William M. Palin , Zhen Zhang

Objective

This study aims to explore the efficacy of Electrophoretic Deposition (EPD) for collagen type I coating on titanium implants and its subsequent mineralization to improve osseointegration and bone regeneration.

Methods

Titanium disks were prepared with a sandblasted, large grit and acid-etched (SLA) surface. EPD was employed to deposit collagen type I onto the titanium surfaces, followed by two modes of mineralization: extra-fibril mineralization (EFM) and inter-fibril mineralization (IFM). Then comprehensive in vitro studies were conducted including surface properties, cell proliferation, osteogenic differentiation, and inflammatory responses.

Results

EPD successfully deposited a uniform collagen layer on titanium surfaces. EFM resulted in deposition of larger, irregularly shaped crystals, while IFM produced controlled, helical fibril mineralization. IFM-treated surfaces exhibited enhanced cell viability, proliferation, and osteogenic differentiation. Both EFM and IFM surfaces triggered higher macrophage activation than SLA surfaces. While EFM primarily induced a stronger M1 pro-inflammatory response, IFM exhibited a more balanced macrophage polarization with upregulated M2 markers at later stages.

Conclusion

EPD, particularly when integrated with IFM, significantly enhances the bioactivity and osteogenic potential of collagen-coated titanium implants. This method surpasses traditional SLA surfaces by stabilizing the collagen layer and creating a biomimetic environment conducive to bone regeneration and healing through a balanced inflammatory response, offering a promising strategy to improve titanium implant performance.

研究目的本研究旨在探讨电泳沉积法（EPD）在钛植入物上涂覆 I 型胶原蛋白的效果，以及随后的矿化过程，以改善骨结合和骨再生：方法：制备的钛盘表面经过喷砂、大颗粒和酸蚀（SLA）处理。采用 EPD 将 I 型胶原蛋白沉积到钛表面，然后进行两种矿化模式：纤维外矿化（EFM）和纤维间矿化（IFM）。然后进行了全面的体外研究，包括表面特性、细胞增殖、成骨分化和炎症反应：结果：EPD 成功地在钛表面沉积了均匀的胶原层。EFM沉积了较大的不规则晶体，而IFM则产生了可控的螺旋状纤维矿化。经 IFM 处理的表面显示出更强的细胞活力、增殖和成骨分化能力。与 SLA 表面相比，EFM 和 IFM 表面都能引发更高的巨噬细胞活化。EFM主要诱导更强的M1促炎反应，而IFM则表现出更平衡的巨噬细胞极化，在后期阶段M2标记物上调：结论：EPD，尤其是与 IFM 结合使用时，可显著增强胶原涂层钛植入物的生物活性和成骨潜力。这种方法超越了传统的 SLA 表面，它稳定了胶原层，并通过平衡的炎症反应创造了有利于骨再生和愈合的仿生环境，为提高钛植入物的性能提供了一种前景广阔的策略。

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引用次数: 0

Preparation and characterization of neural stem cell-loaded conductive hydrogel cochlear implant electrode coatings 神经干细胞负载导电水凝胶人工耳蜗电极涂层的制备和表征。

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-08 DOI: 10.1016/j.bioadv.2024.214109

Zhiyi Wang , Yu Yan , Wenxin Chen , Zhiping Tan , Qingfeng Yan , Qingqing Chen , Xue Ding , Jiahua Shen , Min Gao , Yang Yang , Lulu Yu , Fuzhi Lin , Yong Fu , Xiaoqiang Jin , Xiaohua Yu

Sensorineural deafness is a hearing impairment resulting from damage to the auditory nerve or inner ear hair cells. Currently, cochlear implants (CIs) are widely used as hearing aids for sensorineural deafness patients. A fundamental limitation of cochlear implants (CIs) is that spiral ganglion neurons (SGNs) cannot be replenished. This greatly restricts the rehabilitation of sensorineural deafness. Additionally, the insertion of CIs can cause secondary cochlear damage, worsening the condition of the patients' cochlear. Therefore, a new type of neural stem cells (NSCs) loaded graphene oxide-polyaniline/GelMA (GO-PAni/GelMA) conductive hydrogel electrode for cochlear implant was fabricated via in-situ radical polymerization and cyclic UV curing technique. On the one hand, the hydrogel electrode, as a direct contact layer, helps to avoid the physical hurt for cochlear. On the other hand, NSCs were supplemented via the hydrogel carrier and neuronal differentiation was induced by electrical stimulation, which was validated by the experimental results of immunofluorescence, Phalloidin Staining and RT-qPCR. Furthermore, based on RNA sequencing and transcriptome analysis, we hypothesized that the neuronal differentiation of NSCs was adjusted by the calcium signaling pathway and GABAergic synapse. Overall, our cell loading conductive hydrogel electrode may be an effective solution to sensorineural deafness. The revelation of the mechanism of neuronal differentiation promoted by electrical stimulation provides a basis for further sensorineural deafness treatment using conductive hydrogel CI electrode.

感音神经性耳聋是一种因听觉神经或内耳毛细胞受损而导致的听力障碍。目前，人工耳蜗（CI）被广泛用作感音神经性耳聋患者的助听器。人工耳蜗（CI）的一个基本局限是螺旋神经节神经元（SGN）无法补充。这极大地限制了感音神经性耳聋的康复。此外，植入人工耳蜗还会造成继发性耳蜗损伤，使患者的耳蜗状况恶化。因此，本研究通过原位自由基聚合和循环紫外固化技术制备了一种用于人工耳蜗植入的新型神经干细胞负载氧化石墨烯-聚苯胺/凝胶MA（GO-PAni/GelMA）导电水凝胶电极。一方面，水凝胶电极作为直接接触层，有助于避免人工耳蜗受到物理伤害。另一方面，通过水凝胶载体补充 NSCs，并通过电刺激诱导神经元分化，免疫荧光、类球蛋白酶染色和 RT-qPCR 的实验结果验证了这一点。此外，根据 RNA 测序和转录组分析，我们推测 NSCs 的神经元分化是由钙信号通路和 GABA 能突触调节的。总之，我们的细胞负载导电水凝胶电极可能是治疗感音神经性耳聋的有效方法。电刺激促进神经元分化机制的揭示为进一步利用导电水凝胶CI电极治疗感音神经性耳聋提供了基础。

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引用次数: 0

Processing and properties of graphene-reinforced polylactic acid nanocomposites for bioelectronic and tissue regenerative functions 用于生物电子和组织再生功能的石墨烯增强聚乳酸纳米复合材料的加工和性能。

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-08 DOI: 10.1016/j.bioadv.2024.214113

Nan Li , Mengjia Wang , Haoyu Luo , Stephen D. Tse , Yun Gao , Zhen Zhu , Hongxuan Guo , Longbing He , Chao Zhu , Kuibo Yin , Litao Sun , Jie Guo , Hua Hong

An in-situ polymer-solution-processing approach enables the efficient production of uniform graphene-reinforced polylactic acid (G-PLA) nanocomposites with notable physical and biomedical properties. The approach effectively enhances the interfacial bonding between graphene and PLA by creating graphene dangling bonds and defects during exfoliation. As a result, an 182 % increase in Young's modulus and an 85 % increase in tensile strength can be achieved in G-PLA. Only 0.5 wt% graphene addition can reduce the contact angle of the composite from 75.3 to 70.4 and reduce its oxygen permeability by 23 %. The improved hydrophilicity, hermeticity, and mechanical properties make G-PLA an excellent encapsulation material for implantable bioelectronics. Moreover, the composite surface attributes and cell behaviors at the material-tissue interface are investigated histologically through the culture of stem cells on as-synthesized G-PLA. G-PLA composites can significantly boost cell proliferation and regulate cell differentiation towards vascular endothelium, offering tissue regeneration at the surface of implants to recover the injured tissues. The degradation rate of G-PLA nanocomposite can also be regulated since the graphene slows down the autocatalytic chain splitting induced by the terminal carboxylic acid groups of PLA. Therefore, such G-PLA nanocomposites with physical and biomedical properties regulated by graphene loading enable the development of next-generation implantable electronic systems providing both sensing and tissue engineering functions for complicated applications such as implanted sensors monitoring the healing of fractured bones or intracranial pressure.

一种原位聚合物溶液加工方法能够高效生产出具有显著物理和生物医学特性的均匀石墨烯增强聚乳酸（G-PLA）纳米复合材料。该方法通过在剥离过程中产生石墨烯悬挂键和缺陷，有效增强了石墨烯和聚乳酸之间的界面结合。因此，G-PLA 的杨氏模量提高了 182%，拉伸强度提高了 85%。仅添加 0.5 wt% 的石墨烯就能将复合材料的接触角从 75.3 降低到 70.4，并将其透氧性降低 23%。亲水性、密封性和机械性能的改善使 G-PLA 成为植入式生物电子器件的绝佳封装材料。此外，还通过在合成的 G-PLA 上培养干细胞，从组织学角度研究了复合材料的表面属性和细胞在材料-组织界面上的行为。G-PLA复合材料能显著促进细胞增殖并调节细胞向血管内皮分化，从而实现植入物表面的组织再生，恢复受伤组织。由于石墨烯能减缓聚乳酸末端羧酸基团诱导的自催化链分裂，G-PLA 纳米复合材料的降解速率也能得到调节。因此，这种由石墨烯负载调控物理和生物医学特性的 G-PLA 纳米复合材料可用于开发具有传感和组织工程功能的下一代植入式电子系统，以满足诸如监测骨折愈合或颅内压的植入式传感器等复杂应用的需要。

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引用次数: 0

5-Fluorouracil/curcumin loaded silk fibroin hydrogel for the adjuvant therapy in colorectal cancer 5-氟尿嘧啶/姜黄素负载丝素水凝胶用于大肠癌的辅助治疗

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-06 DOI: 10.1016/j.bioadv.2024.214108

Jingxuan Yuan , Weiwei Sun , Zhibin Zhang , Yan Wang , Dandan Huang , Donglin Ren , Hong Chen , Xiaoqin Wang , Gang Li , Zhifen Han

This study employed silk fibroin (SF) as a carrier material to encapsulate curcumin (CUR) and 5-fluorouracil (5-FU), forming a highly effective drug-loaded hydrogel. The process involved mixing SF solution containing 5-FU with curcumin solution dissolved in acetone (AC), leading to the formation of composite drug-loaded nanospheres with particle sizes ranging from 77.87 nm to 299.22 nm, demonstrated enhanced permeability and retention (EPR) effects, enabling passive targeting of solid tumors. After the formation of the nanospheres, they were dispersed into a solution containing SF and polyethylene glycol (PEG). Following gelation and PEG removal, a SF hydrogel loaded with 5-FU and CUR (5-FU/CUR@SF hydrogel) was obtained. Results indicated that the 5-FU/CUR@SF hydrogel exhibited excellent drug release properties, with 5-FU and CUR achieving sustained release of 59.66 ± 3.76 % and 47.94 ± 5.03 %, respectively, over a 400-h of sustainable releasing period. Human colorectal cancer cell line (HT-29) and normal human colon epithelial cell line (NCM-460) were cultured with the 5-FU/CUR@SF hydrogel, resulting an apoptosis rate of only 17.38 ± 1.98 % for NCM-460 cells, whereas the apoptosis rate for HT-29 cells significantly increased to 72.31 ± 2.18 %, and its cell viability dropped to 59.77 ± 0.55 %. These findings suggest that the 5-FU/CUR@SF hydrogel exhibits low cytotoxicity toward normal NCM-460 cells, while exerting significant and sustained inhibitory effects on HT-29 cancer cells. In conclusion, the SF-based drug-loaded composite hydrogel holds great potential as a novel adjuvant therapeutic strategy for the treatment of CRC.

本研究以丝素（SF）为载体材料，包封姜黄素（CUR）和5-氟尿嘧啶（5-FU），形成高效的载药水凝胶。该方法将含有5-FU的SF溶液与溶解于丙酮（AC）的姜黄素溶液混合，形成粒径在77.87 nm至299.22 nm之间的复合载药纳米球，具有增强的渗透性和滞留性（EPR）作用，能够被动靶向实体肿瘤。纳米球形成后，将其分散到含有SF和聚乙二醇（PEG）的溶液中。凝胶化和去除PEG后，获得装载5-FU和CUR的SF水凝胶（5-FU/CUR@SF水凝胶）。结果表明，5-FU/CUR@SF水凝胶具有优异的释药性能，5-FU和CUR在400 h内的缓释率分别为59.66±3.76%和47.94±5.03%。用5-FU/CUR@SF水凝胶培养人结直肠癌细胞系HT-29和正常人结肠上皮细胞系NCM-460后，NCM-460细胞的凋亡率仅为17.38±1.98%，而HT-29细胞的凋亡率为72.31±2.18%，细胞存活率为59.77±0.55%。这些结果表明，5-FU/CUR@SF水凝胶对正常NCM-460细胞具有较低的细胞毒性，而对HT-29癌细胞具有显著且持续的抑制作用。综上所述，基于sf的载药复合水凝胶作为一种新的CRC辅助治疗策略具有很大的潜力。

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引用次数: 0

Carboxymethyl chitosan/alendronate sodium/Sr2+ modified TiO2 nanotube arrays enhancing osteogenic activity and antibacterial property 羧甲基壳聚糖/阿仑膦酸钠/Sr2+修饰的二氧化钛纳米管阵列可增强成骨活性和抗菌性能。

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications

Pub Date : 2024-11-06 DOI: 10.1016/j.bioadv.2024.214107

Kunpeng Jia , Changpeng Zuo , Yan Xu , Wenfu Ma , Lingtao Wang , Yan Ji , Jie Chen , Qiuyang Zhang , Changjiang Pan , Tingting Liu

Titanium and its alloys are widely used as orthopedic implants owing to their good mechanical properties and excellent corrosion resistance. However, the insufficient osteogenic activity and antibacterial properties hinder their clinical applications. To address these issues, TiO₂ nanotube arrays (TNT) were first fabricated on the TA2 alloy surface via an anodizing technique, and strontium ions (Sr²⁺) were then loaded by hydrothermal reaction (TNT + Sr) and annealing treatment (TNT + A). Subsequently, the polydopamine layer (TNT + PDA) was constructed to immobilize the carboxymethyl chitosan and alendronate sodium (TNT + CA) mixture. The prepared coatings were thoroughly characterized by scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), X-ray photoelectron spectrometer (XPS), attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffractometer (XRD), and water contact angle measurement. The results confirmed that Sr²⁺ ions, polydopamine, and carboxymethyl chitosan/alendronate sodium were successfully immobilized on the nanotubes. The coating of TNT + CA significantly enhanced the hydrophilicity, and effectively delayed the release of Sr²⁺ and alendronate. The TNT + CA coating significantly promoted osteoblast adhesion and proliferation, and up-regulated the expressions of alkaline phosphatase (ALP), osteocalcin (OCN), and osteoblast-specific transcription factor (RUNX2). TNT + CA was able to rapidly induce in situ hydroxyapatite deposition from the simulated body fluid (SBF). Moreover, TNT + CA coating showed inhibition against Escherichia coli and Staphylococcus aureus (especially against Escherichia coli). The prepared TNT + CA coating provides a novel strategy for enhancing bone affinity, improving osteoblast behaviors, and antibacterial properties of titanium-based biomaterials.

钛及其合金具有良好的机械性能和优异的耐腐蚀性，因此被广泛用作骨科植入物。然而，成骨活性和抗菌性能不足阻碍了它们的临床应用。为了解决这些问题，首先通过阳极氧化技术在 TA2 合金表面制造了二氧化钛纳米管阵列（TNT），然后通过水热反应（TNT + Sr）和退火处理（TNT + A）将锶离子（Sr2+）加入其中。随后，通过构建聚多巴胺层（TNT + PDA）来固定羧甲基壳聚糖和阿仑膦酸钠混合物（TNT + CA）。通过扫描电子显微镜（SEM）、能量色散光谱仪（EDS）、X 射线光电子能谱仪（XPS）、衰减全反射-傅立叶变换红外光谱仪（ATR-FTIR）、X 射线衍射仪（XRD）和水接触角测量对制备的涂层进行了全面表征。结果证实，Sr2+ 离子、聚多巴胺和羧甲基壳聚糖/阿仑膦酸钠被成功固定在纳米管上。TNT + CA涂层显著增强了亲水性，并有效延缓了Sr2+和阿仑膦酸钠的释放。TNT + CA涂层能明显促进成骨细胞的粘附和增殖，并上调碱性磷酸酶（ALP）、骨钙素（OCN）和成骨细胞特异性转录因子（RUNX2）的表达。TNT + CA能快速诱导模拟体液（SBF）中羟基磷灰石的原位沉积。此外，TNT + CA涂层对大肠杆菌和金黄色葡萄球菌（尤其是大肠杆菌）有抑制作用。制备的 TNT + CA 涂层为增强钛基生物材料的骨亲和性、改善成骨细胞行为和抗菌性能提供了一种新策略。

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引用次数: 0