Biomaterials

生物材料
  • 文章类型: Journal Article
    对外周神经系统(PNI)的创伤性损伤可导致严重的后果,例如瘫痪。不幸的是,目前的治疗很少允许令人满意的功能恢复。与PNS伤害相关的高医疗费用,工人残疾,和低患者满意度按替代解决方案,超越现行标准。对于桥梁缺损小于30毫米的损伤的治疗,使用合成神经导管(NGC)是有利的。然而,为了开发这种有前途的治疗策略,需要更忠实地模拟神经生理学的体外模型。缺乏具有诸如三维环境和动态共培养的基本要素的临床缩放模型阻碍了该领域的进展。本研究的重点是周围神经系统(PNS)的体外共培养模型的开发,该模型涉及使用功能性生物材料,该材料的微观结构可复制神经形貌。最初,研究了与一小段生物材料(5mm)接触的神经元衍生细胞系(N)和雪旺氏细胞(SC)的行为。随后的调查,使用荧光标记和存活测定,证明了共培养的协同效应。然后将这些优化的参数应用于更长的生物材料(30毫米),相当于临床使用的NGC。获得的结果表明,在临床缩放的生物材料上,可以在7天的时间内维持SC和N的延长共培养。观察一些功能。从长远来看,从这项工作中获得的知识将有助于更好地了解PNS再生过程,并促进未来治疗方法的发展,同时减少对动物实验的依赖。该模型可用于药物筛选并适用于个性化医学试验。最终,这项工作填补了当前研究的关键空白,为研究和推进PNS损伤的治疗提供了一种变革性的方法。
    Traumatic injuries to the peripheral nervous system (PNI) can lead to severe consequences such as paralysis. Unfortunately, current treatments rarely allow for satisfactory functional recovery. The high healthcare costs associated with PNS injuries, worker disability, and low patient satisfaction press for alternative solutions that surpass current standards. For the treatment of injuries with a deficit of less than 30 mm to bridge, the use of synthetic nerve conduits (NGC) is favored. However, to develop such promising therapeutic strategies, in vitro models that more faithfully mimic nerve physiology are needed. The absence of a clinically scaled model with essential elements such as a three-dimension environment and dynamic coculture has hindered progress in this field. The presented research focuses on the development of an in vitro coculture model of the peripheral nervous system (PNS) involving the use of functional biomaterial which microstructure replicates nerve topography. Initially, the behavior of neuron-derived cell lines (N) and Schwann cells (SC) in contact with a short section of biomaterial (5 mm) was studied. Subsequent investigations, using fluorescent markers and survival assays, demonstrated the synergistic effects of coculture. These optimized parameters were then applied to longer biomaterials (30 mm), equivalent to clinically used NGC. The results obtained demonstrated the possibility of maintaining an extended coculture of SC and N over a 7-day period on a clinically scaled biomaterial, observing some functionality. In the long term, the knowledge gained from this work will contribute to a better understanding of the PNS regeneration process and promote the development of future therapeutic approaches while reducing reliance on animal experimentation. This model can be used for drug screening and adapted for personalized medicine trials. Ultimately, this work fills a critical gap in current research, providing a transformative approach to study and advance treatments for PNS injuries.
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  • 文章类型: Journal Article
    用于牙周炎和种植体周围炎的骨缺损的重建治疗的最新进展依赖于高度多孔的可生物降解的生物气凝胶的开发,用于引导骨再生。这项工作的目的是评估体外诱导牙周起源细胞(人牙囊间充质细胞,DFMSC)由纳米羟基磷灰石/壳聚糖(nHAp/CS)生物气凝胶促进,通过可持续技术(超临界CO2)进行纯化和灭菌。此外,初步评估了nHAp/CS生物气凝胶的体内骨再生能力,作为大鼠颅骨骨缺损模型的概念验证。接种在nHAp/CS和CS支架(对照材料)上的DFMSC的DNA含量的定量显示从培养的第14天到第21天显著增加。通过共聚焦激光扫描显微镜分析(CLSM)证实了这些结果。此外,碱性磷酸酶(ALP)活性在第21天显著增加,这两种材料也是如此。此外,与CS支架和对照相比,nHAp的存在在21天后促进了成骨基因的表达。培养21天的CLSM图像还显示OPN在nHAp/CS表面上的沉积增加。通过显微CT和组织学分析评估体内骨形成。体内评估显示,与CS和空对照相比,nHAp/CS测试组的骨体积显着增加,以及nHAp/CS结构内更高的新骨形成和钙沉积。总的来说,本研究表明,nHAp/CS生物气凝胶可以为牙周和种植体周围骨再生治疗提供潜在的解决方案,因为体外结果表明它为DFMSC增殖和成骨分化提供了有利条件,而体内结果证实,它促进了更高的骨向内生长。
    The most recent progress in reconstructive therapy for the management of periodontitis and peri-implantitis bone defects has relied on the development of highly porous biodegradable bioaerogels for guided bone regeneration. The objective of this work was to evaluate in vitro the osteoinduction of periodontal-originating cells (human dental follicle mesenchymal cells, DFMSCs) promoted by a nano-hydroxyapatite/chitosan (nHAp/CS) bioaerogel, which was purified and sterilized by a sustainable technique (supercritical CO2). Moreover, the in vivo bone regeneration capacity of the nHAp/CS bioaerogel was preliminarily assessed as a proof-of-concept on a rat calvaria bone defect model. The quantification of DNA content of DFMSCs seeded upon nHAp/CS and CS scaffolds (control material) showed a significant increase from the 14th to the 21st day of culture. These results were corroborated through confocal laser scanning microscopy analysis (CLSM). Furthermore, the alkaline phosphatase (ALP) activity increased significantly on the 21st day, similarly for both materials. Moreover, the presence of nHAp promoted a significantly higher expression of osteogenic genes after 21 days when compared to CS scaffolds and control. CLSM images of 21 days of culture also showed an increased deposition of OPN over the nHAp/CS surface. The in vivo bone formation was assessed by microCT and histological analysis. The in vivo evaluation showed a significant increase in bone volume in the nHAp/CS test group when compared to CS and the empty control, as well as higher new bone formation and calcium deposition within the nHAp/CS structure. Overall, the present study showed that the nHAp/CS bioaerogel could offer a potential solution for periodontal and peri-implant bone regeneration treatments since the in vitro results demonstrated that it provided favorable conditions for DFMSC proliferation and osteogenic differentiation, while the in vivo outcomes confirmed that it promoted higher bone ingrowth.
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  • 文章类型: Journal Article
    免疫治疗已发展成为现代癌症治疗的重要方式。不幸的是,检查点抑制剂免疫疗法目前是全身给药,需要频繁给药,这可能会导致毒性和严重,有时是致命的,不良事件。用于口腔癌和口腔潜在恶性疾病的免疫调节剂的局部递送提供了最大治疗潜力和减少的全身不良反应的前景。这篇综述将讨论当前标准护理系统疗法的局限性,并强调局部治疗的研究进展,用于口腔癌和口腔潜在恶性疾病的免疫治疗的肿瘤内递送平台。
    Immunotherapy has developed into an important modality of modern cancer treatment. Unfortunately, checkpoint inhibitor immunotherapies are currently delivered systemically and require frequent administration, which can result in toxicity and severe, sometimes fatal, adverse events. Localized delivery of immunomodulators for oral cancer and oral potentially malignant disorders offers the promise of maximum therapeutic potential and reduced systemic adverse effects. This review will discuss the limitations of current standard-of-care systemic therapies and highlight research advances in localized, intratumoral delivery platforms for immunotherapy for oral cancer and oral potentially malignant disorders.
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  • 文章类型: Journal Article
    生物材料是可以注射的物质,植入,或应用于生物医学应用中的组织表面,并具有与生物系统相互作用以引发治疗反应的能力。基于生物材料的疫苗递送系统具有强大的包装能力,使药物在目标部位持续和局部释放。在整个疫苗接种过程中,它们可以有助于保护,稳定,并指导免疫原,同时还用作佐剂以增强疫苗功效。在这篇文章中,我们全面回顾了生物材料对疫苗发展的贡献。我们首先对生物材料的类型和性质进行分类,详细说明他们的后处理策略,探索几种常见的交付系统,如聚合物纳米颗粒,脂质纳米粒,水凝胶,还有微针.此外,我们研究了生物材料的理化性质和传递途径如何影响免疫反应。值得注意的是,我们深入研究了生物材料作为疫苗佐剂的设计考虑,展示了它们在癌症疫苗开发中的应用,获得性免疫缺陷综合症,流感,2019年冠状病毒病(COVID-19),结核病,疟疾,在这篇综述中,我们重点介绍了生物材料增强疫苗效力的成功实例,并讨论了生物材料在疫苗递送和免疫疗法中的局限性和未来方向。本文旨在让研究人员全面了解生物材料在疫苗开发中的应用,并促进相关领域的进一步发展。
    Biomaterials are substances that can be injected, implanted, or applied to the surface of tissues in biomedical applications and have the ability to interact with biological systems to initiate therapeutic responses. Biomaterial-based vaccine delivery systems possess robust packaging capabilities, enabling sustained and localized drug release at the target site. Throughout the vaccine delivery process, they can contribute to protecting, stabilizing, and guiding the immunogen while also serving as adjuvants to enhance vaccine efficacy. In this article, we provide a comprehensive review of the contributions of biomaterials to the advancement of vaccine development. We begin by categorizing biomaterial types and properties, detailing their reprocessing strategies, and exploring several common delivery systems, such as polymeric nanoparticles, lipid nanoparticles, hydrogels, and microneedles. Additionally, we investigated how the physicochemical properties and delivery routes of biomaterials influence immune responses. Notably, we delve into the design considerations of biomaterials as vaccine adjuvants, showcasing their application in vaccine development for cancer, acquired immunodeficiency syndrome, influenza, corona virus disease 2019 (COVID-19), tuberculosis, malaria, and hepatitis B. Throughout this review, we highlight successful instances where biomaterials have enhanced vaccine efficacy and discuss the limitations and future directions of biomaterials in vaccine delivery and immunotherapy. This review aims to offer researchers a comprehensive understanding of the application of biomaterials in vaccine development and stimulate further progress in related fields.
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  • 文章类型: Journal Article
    在组织工程领域,3D打印的形状记忆聚合物(SMP)引起了越来越多的兴趣。了解这些3D打印的SMP如何降解对于它们在临床中的使用至关重要。因为材料特性的微小变化可以显著改变它们在体内植入后的行为。通过体外水解检查3D打印丙烯酸酯化聚(甘油-十二烷二酸酯)(APGD)的降解,酶,和体内皮下植入试验。评估了三种APGD制造方式以确定降解的差异。材料挤出样品在2个月时显示出明显更大的质量和体积损失,与激光切割和大桶光聚合样品相比,在酶和体内降解下。严重的,降解的PGD的熔融转变温度在体外随时间增加,但不是在体内。与对照组相比,APGD植入物周围组织的组织学没有明显的炎症迹象,为3D打印APGD设备在临床上的使用提供了有希望的前景。
    In the field of tissue engineering, 3D printed shape memory polymers (SMPs) are drawing increased interest. Understanding how these 3D printed SMPs degrade is critical for their use in the clinic, as small changes in material properties can significantly change how they behave after in vivo implantation. Degradation of 3D printed acrylated poly(glycerol-dodecanedioate) (APGD) was examined via in vitro hydrolytic, enzymatic, and in vivo subcutaneous implantation assays. Three APGD manufacturing modalities were assessed to determine differences in degradation. Material extrusion samples showed significantly larger mass and volume loss at 2 months, compared to lasercut and vat photopolymerization samples, under both enzymatic and in vivo degradation. Critically, melt transition temperatures of degraded PGD increased over time in vitro, but not in vivo. Histology of tissue surrounding APGD implants showed no significant signs of inflammation compared to controls, providing a promising outlook for use of 3D printed APGD devices in the clinic.
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  • 文章类型: Journal Article
    虽然细胞外基质(ECM)长期以来一直被认为是其结构贡献,锚定粘附细胞,提供机械支持,保持组织的完整性,最近的努力阐明了它的动态,倒数,和血管生成的不同特性。ECM调节血管生成信号和机械转导,影响受体激活的程度和程度,控制细胞行为,并作为生物活性大分子的储库。总的来说,这些因素指导形成,成熟,和功能性血管网络的稳定。这篇综述旨在阐明ECM在血管生成中的多功能作用。超越其作为单纯结构材料的传统功能。我们将探索其在信号调制中的参与和协同作用,与各种血管生成因子的相互作用,并强调其在健康和疾病中的重要性。通过捕捉ECM不同功能的本质,我们强调了血管生物学在更广泛背景下的重要性,使新型生物材料的设计能够工程化血管化组织及其潜在的治疗意义。
    While the extracellular matrix (ECM) has long been recognized for its structural contributions, anchoring cells for adhesion, providing mechanical support, and maintaining tissue integrity, recent efforts have elucidated its dynamic, reciprocal, and diverse properties on angiogenesis. The ECM modulates angiogenic signaling and mechanical transduction, influences the extent and degree of receptor activation, controls cellular behaviors, and serves as a reservoir for bioactive macromolecules. Collectively, these factors guide the formation, maturation, and stabilization of a functional vascular network. This review aims to shed light on the versatile roles of the ECM in angiogenesis, transcending its traditional functions as a mere structural material. We will explore its engagement and synergy in signaling modulation, interactions with various angiogenic factors, and highlight its importance in both health and disease. By capturing the essence of the ECM\'s diverse functionalities, we highlight the significance in the broader context of vascular biology, enabling the design of novel biomaterials to engineer vascularized tissues and their potential therapeutic implications.
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  • 文章类型: Journal Article
    在水凝胶基质中进行卵泡的3D培养是基础科学研究以及临床应用(例如生育力保存)的重要新兴工具。为了优化和扩展腔前卵泡的3D培养,需要鉴定简化和改进当前培养程序的生物材料基质。目前,在藻酸盐微珠中微囊化毛囊是最常用的方法。然而,该技术涉及值得注意的手动处理,最适合单个或多个毛囊的封装。作为一种潜在的选择,我们在这里探索不同的基于颗粒的水凝胶基质的适用性,毛囊可以很容易地在可调的3D环境中引入,大量。具体来说,我们研究了微粒藻酸盐和纳米纤维纤维素基质中次级鼠卵泡的生长,有和没有细胞结合线索,并根据基质的粘弹性特性绘制卵泡生长图。我们在基于颗粒的水凝胶中培养卵泡10天,并连续监测其大小,生存,并倾向于挤出卵母细胞。有趣的是,我们观察到,在基于颗粒的基质中,正在生长的卵泡的直径显着增加,与最先进的藻酸盐微囊化相比。另一方面,卵泡在颗粒基质中显示出早期卵母细胞挤出的增加趋势,导致完整卵泡数量显着减少。我们认为这可能是由于营养物质和氧气通过较厚的基质扩散受损引起的,归因于我们的实验设置。尽管如此,我们的发现表明粘弹性,颗粒水凝胶代表了早期卵泡3D培养的有希望的基质。特别是,这些材料可以容易地在先进的培养装置如微灌注系统中实施。
    3D culture of ovarian follicles in hydrogel matrices is an important emerging tool for basic scientific studies as well as clinical applications such as fertility preservation. For optimizing and scaling 3D culture of preantral follicles, there is a need for identifying biomaterial matrices that simplifies and improves the current culture procedures. At present, microencapsulation of follicles in alginate beads is the most commonly used approach. However, this technique involves notable manual handling and is best suited for encapsulation of single or several follicles. As a potential alternative, we here explore the suitability of different particle-based hydrogel matrices, where follicles can easily be introduced in tunable 3D environments, in large numbers. Specifically, we study the growth of secondary murine follicles in microgranular alginate and nanofibrillar cellulose matrices, with and without cell-binding cues, and map follicle growth against the viscoelastic properties of the matrices. We cultured follicles within the particle-based hydrogels for 10 days and continuously monitored their size, survival, and tendency to extrude oocytes. Interestingly, we observed that the diameter of the growing follicles increased significantly in the particle-based matrices, as compared to state-of-the-art alginate micro-encapsulation. On the other hand, the follicles displayed an increased tendency for early oocyte extrusion in the granular matrices, leading to a notable reduction in the number of intact follicles. We propose that this may be caused by impaired diffusion of nutrients and oxygen through thicker matrices, attributable to our experimental setup. Still, our findings suggest that viscoelastic, granular hydrogels represent promising matrices for 3D culture of early-stage ovarian follicles. In particular, these materials may easily be implemented in advanced culturing devices such as micro-perfusion systems.
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  • 文章类型: Journal Article
    缺血事件可以导致急性心肌梗死,它是由不可逆的心脏损伤产生的,由于心脏的再生能力有限而无法恢复。心脏细胞疗法旨在用健康和有功能的细胞替换受损或坏死的细胞。组织工程和心血管再生医学提出了使用模拟天然细胞外环境并改善细胞和组织功能的生物材料的治疗替代方案。这项研究评估了热敏水凝胶的效果,和小鼠胎儿心室心肌细胞包裹在热敏水凝胶中,缺血事件期间心肌细胞再生的收缩功能。开发了壳聚糖和水解胶原蛋白热敏水凝胶,它们的物理和化学特征。同样,通过MTT细胞毒性试验评估了它们的生物相容性,LDH,和他们的溶血能力。水凝胶,和水凝胶内的细胞,被用作低氧条件下原代心肌细胞的干预,以通过测量细胞内钙水平和结合蛋白的表达来确定收缩能力的恢复,例如a-actinin和连接蛋白43。这些结果证明了天然热敏水凝胶恢复缺血性心肌细胞的生物电功能的潜力。
    Ischemic events can culminate in acute myocardial infarction, which is generated by irreversible cardiac lesions that cannot be restored due to the limited regenerative capacity of the heart. Cardiac cell therapy aims to replace injured or necrotic cells with healthy and functional cells. Tissue engineering and cardiovascular regenerative medicine propose therapeutic alternatives using biomaterials that mimic the native extracellular environment and improve cellular and tissue functionality. This investigation evaluates the effect of thermosensitive hydrogels, and murine fetal ventricular cardiomyocytes encapsulated in thermosensitive hydrogels, on the contractile function of cardiomyocyte regeneration during an ischemic event. Chitosan and hydrolyzed collagen thermosensitive hydrogels were developed, and they were physically and chemically characterized. Likewise, their biocompatibility was evaluated through cytotoxicity assays by MTT, LDH, and their hemolytic capacity. The hydrogels, and cells inside the hydrogels, were used as an intervention for primary cardiomyocytes under hypoxic conditions to determine the restoration of the contractile capacity by measuring intracellular calcium levels and the expressions of binding proteins, such as a-actinin and connexin 43. These results evidence the potential of natural thermosensitive hydrogels to restore the bioelectrical functionality of ischemic cardiomyocytes.
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  • 文章类型: Journal Article
    本文提出了一种制备多功能复合生物材料的新方法,并将其应用于先进的生物医学领域。生物材料由磷酸二钙(DCPD)和生物活性硅酸盐玻璃(SiO2/Na2O和SiO2/K2O)组成,含有抗生素硫酸链霉素。通过X射线衍射和衰减全反射傅里叶变换红外光谱对材料进行了深入表征,和zeta电位分析,紫外可见分光光度法,在模拟体液(SBF)溶液中进行离子交换测量。主要结果包括在硅酸盐溶液的影响下将磷酸二钙原位化学转化为磷灰石相和抗生素的掺入。ζ电位显示表面电荷从ζ=-24.6mV降低至ζ=-16.5mV。此外,在37天的时间内观察到抗生素的受控和延长释放,释放浓度高达755ppm。小鼠毒性试验证明了对生物材料的良好耐受性,无明显不良反应。此外,这些生物材料对各种细菌菌株显示出有效的抗菌活性,包括单核细胞增生李斯特菌,金黄色葡萄球菌,大肠杆菌,铜绿假单胞菌,表明它们在组织工程中的潜在用途,药物输送,以及骨科和牙科植入物。通过将抗生素整合到生物材料复合材料中,我们实现了控制释放和延长抗菌疗效。这项研究通过探索创新的合成路线并展示其在再生医学和受控药物递送方面的前景,为推进生物材料的发展做出了贡献。
    This article presents a new method for preparing multifunctional composite biomaterials with applications in advanced biomedical fields. The biomaterials consist of dicalcium phosphate (DCPD) and bioactive silicate glasses (SiO2/Na2O and SiO2/K2O), containing the antibiotic streptomycin sulfate. Materials were deeply characterized by X-ray diffraction and attenuated total reflectance Fourier transform infrared spectroscopy, and zeta potential analysis, UV-visible spectrophotometry, and ion-exchange measurement were applied in a simulating body fluid (SBF) solution. The main results include an in situ chemical transformation of dicalcium phosphate into an apatitic phase under the influence of silicate solutions and the incorporation of the antibiotic. The zeta potential showed a decrease in surface charge from ζ = -24.6 mV to ζ = -16.5 mV. In addition, a controlled and prolonged release of antibiotics was observed over a period of 37 days, with a released concentration of up to 755 ppm. Toxicity tests in mice demonstrated good tolerance of the biomaterials, with no significant adverse effects. Moreover, these biomaterials have shown potent antibacterial activity against various bacterial strains, including Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, suggesting their potential use in tissue engineering, drug delivery, and orthopedic and dental implants. By integrating the antibiotic into the biomaterial composites, we achieved controlled release and prolonged antibacterial efficacy. This research contributes to advancing biomaterials by exploring innovative synthetic routes and showcasing their promise in regenerative medicine and controlled drug delivery.
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  • 文章类型: Journal Article
    世界饥饿越来越严重,而全球生产的三分之一的食物被浪费掉了,永远不会被消费。减少食物浪费对促进食物系统的可持续性至关重要,和改进的食品包装解决方案可以加强这一努力。在智能食品包装中使用生物材料不仅提高了食品的保存和安全性,而且符合当前对生态友好型技术的需求,以减轻气候变化的影响。这篇综述全面概述了基于生物材料创新用途的食品包装领域的发展。它强调了来自自然界的生物材料的潜在用途,包括纤维素,壳聚糖,角蛋白,等。为此目的。详细讨论了各种智能食品包装技术,如活性和智能包装,包括清除添加剂,变色环境指示器,传感器,RFID标签,等。该文章还深入研究了可食用薄膜和涂层的利用,食品包装系统中的纳米颗粒填料和二维材料。此外,它概述了这个动态领域的挑战和机遇,强调持续需要研究和创新,以塑造可持续和智能食品包装解决方案的未来,以提高和监测食品的保质期。
    World hunger is getting worse, while one-third of food produced around the globe is wasted and never consumed. It is vital to reduce food waste to promote the sustainability of food systems, and improved food packaging solutions can augment this effort. The utilization of biomaterials in smart food packaging not only enhances food preservation and safety but also aligns with current demands for eco-friendly technologies to mitigate the impacts of climate change. This review provides a comprehensive overview of the developments in the field of food packaging based on the innovative use of biomaterials. It emphasizes the potential use of biomaterials derived from nature including cellulose, chitosan, keratin, etc. for this purpose. Various smart food packaging technologies such as active and intelligent packaging are discussed in detail including scavenging additives, colour-changing environment indicators, sensors, RFID tags, etc. The article also delves into the utilization of edible films and coatings, nanoparticle fillers and 2D materials in food packaging systems. Furthermore, it outlines the challenges and opportunities in this dynamic domain, emphasizing the ongoing need for research and innovation to shape the future of sustainable and smart food packaging solutions to enhance and monitor the shelf-life of food products.
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